TRISPECIFIC AND/OR TRIVALENT BINDING PROTEINS FOR PREVENTION OR TREATMENT OF HIV INFECTION

Abstract

Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, where in a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.

Claims

1. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]; a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]; a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1[III], and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV]; wherein V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

2. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I] and a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]
and a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III] and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV] wherein: V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain; C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain; C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain; hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers; and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

3. The binding protein of claim 1 or claim 2, wherein the one or more HIV target protein is selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 160.

4. The binding protein of claim 1 or claim 2, wherein the binding protein is trispecific and capable of specifically binding three different epitopes on a single HIV target protein.

5. The binding protein of claim 1 or claim 2, wherein the binding protein is trispecific and capable of specifically binding two different epitopes on a first HIV target protein, and one epitope on a second HIV target protein, wherein the first and second HIV target proteins are different.

6. The binding protein of claim 1 or claim 2, wherein the binding protein is trispecific and capable of specifically binding three different antigen targets.

7. The binding protein of claim 1 or claim 2, wherein the binding protein is capable of inhibiting the function of one or more HIV target proteins.

8. The binding protein of any one of claims 1-7, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

9. The binding protein of any one of claims 1-7, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

10. The binding protein of any one of claims 1-9, wherein V.sub.L1 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

11. The binding protein of any one of claims 1-10, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

12. The binding protein of any one of claims 1-10, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

13. The binding protein of any one of claims 1-12, wherein V.sub.L2 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

14. The binding protein of any one of claims 1-13, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

15. The binding protein of any one of claims 1-13, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

16. The binding protein of any one of claims 1-15, wherein V.sub.L3 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

17. The binding protein of any one of claims 1-16, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

18. The binding protein of any one of claims 1-16, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

19. The binding protein of any one of claims 1-18, wherein V.sub.H1 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

20. The binding protein of any one of claims 1-19, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

21. The binding protein of any one of claims 1-19, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

22. The binding protein of any one of claims 1-21, wherein V.sub.H2 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

23. The binding protein of any one of claims 1-22, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

24. The binding protein of any one of claims 1-22, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

25. The binding protein of any one of claims 1-24, wherein V.sub.H3 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

26. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 266, a CDR-L2 comprising the sequence of SEQ ID NO: 267, and a CDR-L3 comprising the sequence of SEQ ID NO: 268; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 248, a CDR-H2 comprising the sequence of SEQ ID NO: 497, and a CDR-H3 comprising the sequence of SEQ ID NO: 250.

27. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 512, V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 502.

28. The binding protein of any one of claims 1-27, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 512; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 502.

29. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

30. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

31. The binding protein of any one of claims 1-25 and 29-30, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

32. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

33. The binding protein of any one of claims 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

34. The binding protein of any one of claims 1-25 and 32-33, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513, V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

35. The binding protein of claim 1, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

36. The binding protein of claim 1, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

37. The binding protein of claim 1, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

38. The binding protein of claim 1, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

39. The binding protein of claim 1, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H1 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

40. The binding protein of claim 2, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

41. The binding protein of claim 2, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

42. The binding protein of claim 2, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

43. The binding protein of claim 1 or claim 2, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

44. The binding protein of claim 1 or claim 2, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

45. The binding protein of any one of claims 1-44, wherein L.sub.1 comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525).

46. A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I] and a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II] and a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1[III] and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV] wherein: V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; wherein: (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and wherein: (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265.

47. A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I] and a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II] and a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III] and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV] wherein: V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain; C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain; hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; wherein: (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and wherein: (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265.

48. The binding protein of claim 46, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

49. The binding protein of claim 46, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

50. The binding protein of claim 46, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

51. The binding protein of claim 46, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

52. The binding protein of claim 46, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

53. The binding protein of claim 47, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

54. The binding protein of claim 47, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

55. The binding protein of claim 47, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

56. The binding protein of claim 46 or claim 47, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

57. The binding protein of claim 46 or claim 47, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

58. The binding protein of any one of claims 46-57, wherein L.sub.1 comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525).

59. A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein: (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2; (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 9; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10; (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 20; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 19; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18; (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 28 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 28; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 27 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 27; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 25 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 25; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 26 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 26; (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34; (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 44; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 43 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 43; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 41; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 42; (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 52 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 52; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 51 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 49 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 49; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 50; (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 60 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 60; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 59 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 59; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 57 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 57; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 58; (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66; (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74; (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 84; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82; (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:92; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90; (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98; (n) the first polypeptide comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106; (o) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114; (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122; (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130; (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146; (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154; (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162; (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170; (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 180 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 180; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 179 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 179; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 177 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 177; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 178 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; (x) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 188 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 188; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 187 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 187; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 185 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 185; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 186 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 186; (y) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 196 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 196; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 195 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 195; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 193 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 194 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 194; (z) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 204 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 204; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 203 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 201 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 202 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202; (aa) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 212; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 211 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 211; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 209 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 209; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 210 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 210; (bb) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 220 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 219 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 219; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 217 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 217; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 218 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 218; (cc) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 228 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 228; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 227 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 227; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 225 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 225; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 226 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 226; (dd) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 235 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 234 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 234; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 232 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 232; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 233 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; or (ee) first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 243 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 242 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 242; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 240 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 240; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 241 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241.

60. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]; a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]; a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1[III]; and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV]; wherein V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

61. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]; a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]; a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III]; and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV]; wherein V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain; C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain; hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

62. The binding protein of claim 60 or claim 61, wherein the one or more HIV target proteins are selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 160.

63. The binding protein of claim 60 or claim 61, wherein the one or more T cell target proteins are CD3 or CD28.

64. The binding protein of claim 60 or claim 61, wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different epitopes on a single T cell target protein.

65. The binding protein of claim 60 or claim 61, wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different T cell target proteins.

66. The binding protein of claim 60 or claim 61, wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different epitopes on a single HIV target protein.

67. The binding protein of claim 60 or claim 61, wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different HIV target proteins.

68. The binding protein of claim 60 or claim 61, wherein the first and second polypeptide chains form two antigen binding sites that specifically target two T cell target proteins, and the third and fourth polypeptide chains form an antigen binding site that specifically binds an HIV target protein.

69. The binding protein of any one of claims 60-68, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

70. The binding protein of any one of claims 60-68, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

71. The binding protein of any one of claims 60-70, wherein V.sub.L1 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

72. The binding protein of any one of claims 60-71, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

73. The binding protein of any one of claims 60-71, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

74. The binding protein of any one of claims 60-73, wherein V.sub.L2 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

75. The binding protein of any one of claims 60-74, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

76. The binding protein of any one of claims 60-74, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

77. The binding protein of any one of claims 60-76, wherein V.sub.L3 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

78. The binding protein of any one of claims 60-77, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

79. The binding protein of any one of claims 60-77, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

80. The binding protein of any one of claims 60-79, wherein V.sub.H1 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

81. The binding protein of any one of claims 60-80, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

82. The binding protein of any one of claims 60-80, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

83. The binding protein of any one of claims 60-82, wherein V.sub.H2 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

84. The binding protein of any one of claims 60-83, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

85. The binding protein of any one of claims 60-83, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

86. The binding protein of any one of claims 60-85, wherein V.sub.H3 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

87. The binding protein of any one of claims 60-86, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

88. The binding protein of any one of claims 60-86, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

89. The binding protein of any one of claims 60-88, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

90. The binding protein of any one of claims 60-86, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

91. The binding protein of any one of claims 60-86, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

92. The binding protein of any one of claims 60-86 and 90-91, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

93. The binding protein of claim 60, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

94. The binding protein of claim 60, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

95. The binding protein of claim 60, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

96. The binding protein of claim 60, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

97. The binding protein of claim 60, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

98. The binding protein of claim 61, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

99. The binding protein of claim 61, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

100. The binding protein of claim 61, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

101. The binding protein of claim 60 or claim 61, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

102. The binding protein of claim 60 or claim 61, wherein L.sub.1, L.sub.2, L3, or L.sub.4 are each independently at least one amino acid in length.

103. The binding protein of any one of claims 60-102, wherein L.sub.1 is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299).

104. A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I] and a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II] and a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1[III] and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV] wherein: V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; wherein: (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and wherein: (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487.

105. A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I] and a second polypeptide chain comprises a structure represented by the formula:
V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II] and a third polypeptide chain comprises a structure represented by the formula:
V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III] and a fourth polypeptide chain comprises a structure represented by the formula:
V.sub.L3-C.sub.L[IV] wherein: V.sub.L1 is a first immunoglobulin light chain variable domain; V.sub.L2 is a second immunoglobulin light chain variable domain; V.sub.L3 is a third immunoglobulin light chain variable domain; V.sub.H1 is a first immunoglobulin heavy chain variable domain; V.sub.H2 is a second immunoglobulin heavy chain variable domain; V.sub.H3 is a third immunoglobulin heavy chain variable domain; C.sub.L is an immunoglobulin light chain constant domain; C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain; C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain; hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers; wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; wherein: (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and wherein: (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487.

106. The binding protein of claim 104, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

107. The binding protein of claim 104, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

108. The binding protein of claim 104, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

109. The binding protein of claim 104, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

110. The binding protein of claim 104, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H1 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

111. The binding protein of claim 105, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

112. The binding protein of claim 105, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

113. The binding protein of claim 105, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

114. The binding protein of claim 104 or claim 105, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

115. The binding protein of claim 104 or claim 105, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

116. The binding protein of any one of claims 104-115, wherein L.sub.1 is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299).

117. A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein: (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 305 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 305; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 304 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 302 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 302; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 303 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303; (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 313 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 313; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 312 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 312; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 310 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 310; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 311 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 311; (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 321 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 321; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 320 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 320; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 318 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 318; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 319 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319; (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 329 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 329; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 328 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 328; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 326 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 326; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 327 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 327; (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 337 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 336 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 336; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 334 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 334; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 335 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 335; (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 345 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 345; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 344 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 344; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 342 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 342; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 343 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 343; (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 353 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 353; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:352; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 350 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 350; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 351 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 351; (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 361 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 361; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 360 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 360; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 358 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 358; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 359 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 359; (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 369 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 369; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 368 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 368; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 366 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 366; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 367 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 367; (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 377 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 377; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 376 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 376; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 374 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 374; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 375 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 375; (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 385 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 385; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 384 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 384; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 382 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 382; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 383 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 383; (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 393 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 393; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 392 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 392; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 390 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 390; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 391 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 391; (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 401 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 401; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 400 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 400; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 398 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 398; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 399 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 399; (n) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 409 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 409; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 408 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 408; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 406 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 407 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 407; (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 417 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 417; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 416 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 416; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 414 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 414; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 415 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 415; (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 425 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 425; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 424 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 424; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 422 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 422; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 423 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 423; (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 433 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:433; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 432 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 432; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 430 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 430; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 431 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 431; (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 441 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 441; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 440 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 438 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 438; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 439 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439; (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 449 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 449; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 448 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 448; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 446 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 446; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 447 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 447, (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 457 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 457; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 456 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 456; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 454 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 454; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 455 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 455; (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 465 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 465; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 464 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 464; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 462 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 462; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 463 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 463; or (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 473 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 473; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 472 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 472; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 470 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 470; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 471 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 471.

118. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding protein of any one of claims 1-117.

119. An expression vector comprising the nucleic acid molecule of claim 118.

120. An isolated host cell comprising the nucleic acid molecule of claim 118.

121. An isolated host cell comprising the expression vector of claim 119.

122. The isolated host cell of claim 120 or claim 121, wherein the host cell is a mammalian cell or an insect cell.

123. A vector system comprising one or more vectors encoding a first, second, third, and fourth polypeptide chain of a binding protein of any one of claims 1-117.

124. The vector system of claim 123, wherein the vector system comprises a first vector encoding the first polypeptide chain of the binding protein, a second vector encoding the second polypeptide chain of the binding protein, a third vector encoding the third polypeptide chain of the binding protein, and a fourth vector encoding the fourth polypeptide chain of the binding protein.

125. The vector system of claim 123, wherein the vector system comprises a first vector encoding the first and second polypeptide chains of the binding protein, and a second vector encoding the third and fourth polypeptide chains of the binding protein.

126. The vector system of any one of claims 123-125, wherein the one or more vectors are expression vectors.

127. An isolated host cell comprising the vector system of any one of claims 123-126.

128. The isolated host cell of claim 127, wherein the host cell is a mammalian cell or an insect cell.

129. A method of producing a binding protein, the method comprising: a) culturing a host cell of any one of claims 120-122 and claims 127-128 under conditions such that the host cell expresses the binding protein; and b) isolating the binding protein from the host cell.

130. A method of preventing and/or treating HIV infection in a patient comprising administering to the patient a therapeutically effective amount of at least one binding protein of any one of claims 1-117.

131. The method of claim 130, wherein the binding protein is co-administered with standard anti-retroviral therapy.

132. The method of claim 130 or claim 131, wherein administration of the at least one binding protein results in the neutralization of one or more HIV virions.

133. The method of any one of claims 130-132, wherein administration of the at least one binding protein results in the elimination of one or more latently and/or chronically HIV-infected cells in the patient.

134. The method of any one of claims 130-133, wherein the patient is a human.

135. The binding protein of any one of claims 1-117 for the prevention or treatment of an HIV infection in a patient.

136. The binding protein of claim 135, wherein the binding protein is co-administered with standard anti-retroviral therapy.

137. The binding protein of claim 135 or claim 136, wherein the binding protein causes the neutralization of one or more HIV virions in the patient.

138. The binding protein of any one of claims 135-137, wherein the binding protein causes the elimination of one or more latently and/or chronically HIV-infected cells in the patient.

139. The binding protein of any one of claims 135-138, wherein the patient is a human.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0144] FIGS. 1A-D show schematic representations of trispecific binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind three different epitopes on one or more antigens, wherein a first pair of polypeptides possess dual variable domains having a cross-over orientation forming two antigen binding sites (comprising V.sub.H1-V.sub.L1 and V.sub.H2-V.sub.L2) and wherein a second pair of polypeptides possess a single antigen binding site (comprising V.sub.H3-V.sub.L3), in accordance with some embodiments. FIG. 1A shows a trispecific binding protein comprising a knobs-into-holes modification, wherein the knob is on the first pair of polypeptides. FIG. 1B shows a trispecific binding protein comprising a knobs-into-holes modification, wherein the knob is on the second pair of polypeptides. FIG. 1C shows the orientation of variable domains on the polypeptide chains, and the knob/hole orientation for binding proteins 1-31 shown in Tables 1 and 2. Heavy chain A (e.g., a third polypeptide chain of the present disclosure) indicates the variable domain of heavy chain A. Light chain A (e.g., a fourth polypeptide chain of the present disclosure) indicates the variable domain of light chain A. Heavy chain B (e.g., a second polypeptide chain of the present disclosure) indicates variable domain 1 and variable domain 2 of heavy chain B. Light chain B (e.g., a first polypeptide chain of the present disclosure) indicates variable domain 1 and variable domain 2 of light chain B. FIG. 1D shows the orientation of variable domains on the polypeptide chains, and the knob/hole orientation for binding proteins 32-53 shown in Tables 1 and 2. Heavy chain A (e.g., a third polypeptide chain of the present disclosure) indicates the variable domain of heavy chain A. Light chain A (e.g., a fourth polypeptide chain of the present disclosure) indicates the variable domain of light chain A. Heavy chain B (e.g., a second polypeptide chain of the present disclosure) indicates variable domain 1 and variable domain 2 of heavy chain B. Light chain B (e.g., a first polypeptide chain of the present disclosure) indicates variable domain 1 and variable domain 2 of light chain B.

[0145] FIGS. 2A-B show purification of three trispecific binding proteins first using affinity chromatography, and then using preparative size exclusion chromatography. FIG. 2A shows the elution profile of the trispecific binding proteins during purification using protein A affinity chromatography. FIG. 2B shows purification of monomeric proteins by Superdex200 size exclusion chromatography.

[0146] FIGS. 3A-B show purification of the MPER Ab, CD4BS Ab b, and V1/V2 directed Ab a parental antibodies first using affinity chromatography, and then using preparative size exclusion chromatography. FIG. 3A shows the elution profile of the parental antibodies during purification using protein A affinity chromatography. FIG. 3B shows purification of monomeric proteins by Superdex200 size exclusion chromatography.

[0147] FIGS. 4A-B show the size exclusion chromatography profiles of bispecific and trispecific binding proteins. FIG. 4A shows the size exclusion chromatography profiles of the bispecific binding proteins. FIG. 4B shows the size exclusion chromatography profiles of the trispecific binding proteins.

[0148] FIG. 5 shows the Biacore sensograms of the binding kinetics of three trispecific binding proteins and the parental MPER Ab antibody for an HIV gp41-derived peptide (the MPER binding site), as assessed by the standard Biacore-based kinetic assay.

[0149] FIG. 6 shows the Biacore sensograms of the binding kinetics of three trispecific binding proteins and the parental CD4BS Ab b antibody for recombinant HIV gp120, as assessed by the standard Biacore-based kinetic assay.

[0150] FIG. 7 shows the results of a pharmacokinetic (PK) study of the indicated proteins after intravenous (IV) injection in rhesus macaques.

[0151] FIGS. 8A-8B show schematic representations of trispecific T-cell engagers, in accordance with some embodiments. The binding sites are indicated by the dotted circles.

[0152] FIG. 9 shows binding properties of the trispecific binding proteins Binding Protein 32 and CD3?CD28/CD4BS Ab b to CD3 (CD3E represents CD3epsilon protein; CD3D represents CD3delta protein), CD28, and Resurfaced Stabilized Core 3 (RSC3) protein of gp120, as well as a negative control (human IgG).

[0153] FIG. 10 shows CD8 T-cell activation using the trispecific proteins Binding Protein 32 and CD3?CD28/CD4BS Ab b compared to the parental CD4BS IgG4 antibody, as well as a negative control (No mAb).

[0154] FIG. 11 shows CD4 T-cell activation using the trispecific proteins Binding Protein 32 and CD3?CD28/CD4BS Ab b compared to the parental CD4BS IgG4 antibody, as well as a negative control (No mAb).

[0155] FIG. 12 shows CD3 downregulation after T cell activation by the trispecific proteins Binding Protein 32 and CD3?CD28/CD4BS Ab b compared to the parental CD4BS IgG4 antibody, as well as a negative control (No mAb).

[0156] FIGS. 13A-C show fluorescence-activated cell sorting (FACS)-based cytotoxicity assay results for trispecific binding proteins against latently infected HIV-1.sup.+ T cells. FIG. 13A shows the results for trispecific binding proteins incubated with CEM-BaL cells. FIG. 13B shows the results for trispecific binding proteins incubated with ACH2 cells. FIG. 13C shows the results for trispecific binding proteins incubated with J1.1 cells.

DETAILED DESCRIPTION

[0157] The present disclosure provides trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind to one or more human immunodeficiency virus (HIV) target proteins and/or one or more T-cell receptor target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain.

[0158] The following description sets forth exemplary methods, parameters, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.

Definitions

[0159] As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0160] The term polynucleotide as used herein refers to single-stranded or double-stranded nucleic acid polymers of at least 10 nucleotides in length. In certain embodiments, the nucleotides comprising the polynucleotide can be ribonucleotides or deoxyribonucleotides or a modified form of either type of nucleotide. Such modifications include base modifications such as bromuridine, ribose modifications such as arabinoside and 2,3-dideoxyribose, and internucleotide linkage modifications such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phoshoraniladate and phosphoroamidate. The term polynucleotide specifically includes single-stranded and double-stranded forms of DNA.

[0161] An isolated polynucleotide is a polynucleotide of genomic, cDNA, or synthetic origin or some combination thereof, which: (1) is not associated with all or a portion of a polynucleotide in which the isolated polynucleotide is found in nature, (2) is linked to a polynucleotide to which it is not linked in nature, or (3) does not occur in nature as part of a larger sequence.

[0162] An isolated polypeptide is one that: (1) is free of at least some other polypeptides with which it would normally be found, (2) is essentially free of other polypeptides from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is not associated (by covalent or noncovalent interaction) with portions of a polypeptide with which the isolated polypeptide is associated in nature, (6) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (7) does not occur in nature. Such an isolated polypeptide can be encoded by genomic DNA, cDNA, mRNA or other RNA, of synthetic origin, or any combination thereof. Preferably, the isolated polypeptide is substantially free from polypeptides or other contaminants that are found in its natural environment that would interfere with its use (therapeutic, diagnostic, prophylactic, research or otherwise).

[0163] Naturally occurring antibodies typically comprise a tetramer. Each such tetramer is typically composed of two identical pairs of polypeptide chains, each pair having one full-length light chain (typically having a molecular weight of about 25 kDa) and one full-length heavy chain (typically having a molecular weight of about 50-70 kDa). The terms heavy chain and light chain as used herein refer to any immunoglobulin polypeptide having sufficient variable domain sequence to confer specificity for a target antigen. The amino-terminal portion of each light and heavy chain typically includes a variable domain of about 100 to 110 or more amino acids that typically is responsible for antigen recognition. The carboxy-terminal portion of each chain typically defines a constant domain responsible for effector function. Thus, in a naturally occurring antibody, a full-length heavy chain immunoglobulin polypeptide includes a variable domain (V.sub.H) and three constant domains (C.sub.H1, C.sub.H2, and C.sub.H3), wherein the V.sub.H domain is at the amino-terminus of the polypeptide and the C.sub.H3 domain is at the carboxyl-terminus, and a full-length light chain immunoglobulin polypeptide includes a variable domain (V.sub.L) and a constant domain (C.sub.L), wherein the V.sub.L domain is at the amino-terminus of the polypeptide and the C.sub.L domain is at the carboxyl-terminus.

[0164] Human light chains are typically classified as kappa and lambda light chains, and human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. IgG has several subclasses, including, but not limited to, IgG1, IgG2, IgG3, and IgG4, IgM has subclasses including, but not limited to, IgM1 and IgM2. IgA is similarly subdivided into subclasses including, but not limited to, IgA1 and IgA2. Within full-length light and heavy chains, the variable and constant domains typically are joined by a J region of about 12 or more amino acids, with the heavy chain also including a D region of about 10 more amino acids. See, e.g., FUNDAMENTAL IMMUNOLOGY (Paul, W., ed., Raven Press, 2nd ed., 1989), which is incorporated by reference in its entirety for all purposes. The variable regions of each light/heavy chain pair typically form an antigen binding site. The variable domains of naturally occurring antibodies typically exhibit the same general structure of relatively conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CDRs. The CDRs from the two chains of each pair typically are aligned by the framework regions, which may enable binding to a specific epitope. From the amino-terminus to the carboxyl-terminus, both light and heavy chain variable domains typically comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0165] The term CDR set refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Kabat et al., SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Chothia and coworkers (Chothia and Lesk, 1987, J. Mol. Biol. 196: 901-17; Chothia et al., 1989, Nature 342: 877-83) found that certain sub-portions within Kabat CDRs adopt nearly identical peptide backbone conformations, despite having great diversity at the level of amino acid sequence. These sub-portions were designated as L1, L2, and L3 or H1, H2, and H3 where the L and the H designates the light chain and the heavy chain regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan, 1995, FASEB J. 9: 133-39; MacCallum, 1996, J. Mol. Biol. 262(5): 732-45; and Lefranc, 2003, Dev. Comp. Immunol. 27: 55-77. Still other CDR boundary definitions may not strictly follow one of the herein systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, although certain embodiments use Kabat or Chothia defined CDRs. Identification of predicted CDRs using the amino acid sequence is well known in the field, such as in Martin, A. C. Protein sequence and structure analysis of antibody variable domains, In Antibody Engineering, Vol. 2. Kontermann R., D?bel S., eds. Springer-Verlag, Berlin, p. 33-51 (2010). The amino acid sequence of the heavy and/or light chain variable domain may be also inspected to identify the sequences of the CDRs by other conventional methods, e.g., by comparison to known amino acid sequences of other heavy and light chain variable regions to determine the regions of sequence hypervariability. The numbered sequences may be aligned by eye, or by employing an alignment program such as one of the CLUSTAL suite of programs, as described in Thompson, 1994, Nucleic Acids Res. 22: 4673-80. Molecular models are conventionally used to correctly delineate framework and CDR regions and thus correct the sequence-based assignments.

[0166] The term Fc as used herein refers to a molecule comprising the sequence of a non-antigen-binding fragment resulting from digestion of an antibody or produced by other means, whether in monomeric or multimeric form, and can contain the hinge region. The original immunoglobulin source of the native Fc is preferably of human origin and can be any of the immunoglobulins, although IgG1 and IgG2 are preferred. Fc molecules are made up of monomeric polypeptides that can be linked into dimeric or multimeric forms by covalent (i.e., disulfide bonds) and non-covalent association. The number of intermolecular disulfide bonds between monomeric subunits of native Fc molecules ranges from 1 to 4 depending on class (e.g., IgG, IgA, and IgE) or subclass (e.g., IgG1, IgG2, IgG3, IgA1, and IgGA2). One example of a Fc is a disulfide-bonded dimer resulting from papain digestion of an IgG. The term Fc as used herein is generic to the monomeric, dimeric, and multimeric forms.

[0167] A F(ab) fragment typically includes one light chain and the V.sub.H and C.sub.H1 domains of one heavy chain, wherein the V.sub.H-C.sub.H1 heavy chain portion of the F(ab) fragment cannot form a disulfide bond with another heavy chain polypeptide. As used herein, a F(ab) fragment can also include one light chain containing two variable domains separated by an amino acid linker and one heavy chain containing two variable domains separated by an amino acid linker and a C.sub.H1 domain.

[0168] A F(ab) fragment typically includes one light chain and a portion of one heavy chain that contains more of the constant region (between the C.sub.H1 and C.sub.H2 domains), such that an interchain disulfide bond can be formed between two heavy chains to form a F(ab).sub.2 molecule.

[0169] The term binding protein as used herein refers to a non-naturally occurring (or recombinant or engineered) molecule that specifically binds to at least one target antigen, and which comprises four polypeptide chains that form at least three antigen binding sites, wherein a first polypeptide chain has a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain has a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]

and a third polypeptide chain has a structure represented by the formula:

V.sub.H3-C.sub.H1[III]

and a fourth polypeptide chain has a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0170] A recombinant molecule is one that has been prepared, expressed, created, or isolated by recombinant means.

[0171] One embodiment of the disclosure provides binding proteins having biological and immunological specificity to between one and three target antigens. Another embodiment of the disclosure provides nucleic acid molecules comprising nucleotide sequences encoding polypeptide chains that form such binding proteins. Another embodiment of the disclosure provides expression vectors comprising nucleic acid molecules comprising nucleotide sequences encoding polypeptide chains that form such binding proteins. Yet another embodiment of the disclosure provides host cells that express such binding proteins (i.e., comprising nucleic acid molecules or vectors encoding polypeptide chains that form such binding proteins).

[0172] The term swapability as used herein refers to the interchangeability of variable domains within the binding protein format and with retention of folding and ultimate binding affinity. Full swapability refers to the ability to swap the order of both V.sub.H1 and V.sub.H2 domains, and therefore the order of V.sub.L1 and V.sub.L2 domains, in the polypeptide chain of formula I or the polypeptide chain of formula II (i.e., to reverse the order) while maintaining full functionality of the binding protein as evidenced by the retention of binding affinity. Furthermore, it should be noted that the designations V.sub.H and V.sub.L refer only to the domain's location on a particular protein chain in the final format. For example, V.sub.H1 and V.sub.H2 could be derived from V.sub.L1 and V.sub.L2 domains in parent antibodies and placed into the V.sub.H1 and V.sub.H2 positions in the binding protein. Likewise, V.sub.L1 and V.sub.L2 could be derived from V.sub.H1 and V.sub.H2 domains in parent antibodies and placed in the V.sub.H1 and V.sub.H2 positions in the binding protein. Thus, the V.sub.H and V.sub.L designations refer to the present location and not the original location in a parent antibody. V.sub.H and V.sub.L domains are therefore swappable.

[0173] The term antigen or target antigen or antigen target as used herein refers to a molecule or a portion of a molecule that is capable of being bound by a binding protein, and additionally is capable of being used in an animal to produce antibodies capable of binding to an epitope of that antigen. A target antigen may have one or more epitopes. With respect to each target antigen recognized by a binding protein, the binding protein is capable of competing with an intact antibody that recognizes the target antigen.

[0174] The term HIV as used herein means Human Immunodeficiency Virus. As used herein, the term HIV infection generally encompasses infection of a host, particularly a human host, by the human immunodeficiency virus (HIV) family of retroviruses including, but not limited to, HIV I, HIV II, HIV III (also known as HTLV-II, LAV-1, LAV-2). HIV can be used herein to refer to any strains, forms, subtypes, clades and variations in the HIV family. Thus, treating HIV infection will encompass the treatment of a person who is a carrier of any of the HIV family of retroviruses or a person who is diagnosed with active AIDS, as well as the treatment or prophylaxis of the AIDS-related conditions in such persons.

[0175] The term AIDS as used herein means Acquired Immunodeficiency Syndrome. AIDS is caused by HIV.

[0176] The terms CD4bs or CD4 binding site refer to the binding site for CD4 (cluster of differentiation 4), which is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells.

[0177] The term CD3 is cluster of differentiation factor 3 polypeptide and is a T-cell surface protein that is typically part of the T cell receptor (TCR) complex.

[0178] CD28 is cluster of differentiation 28 polypeptide and is a T-cell surface protein that provides co-stimulatory signals for T-cell activation and survival.

[0179] The term glycoprotein 160 or gp160 protein refers to the envelope glycoprotein complex of HIV and which is a homotrimer that is cleaved into gp120 and gp41 subunits.

[0180] The term MPER refers to the membrane-proximal external region of glycoprotein 41 (gp41), which is a subunit of the envelope protein complex of retroviruses, including HIV.

[0181] The term glycan refers to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan. In the disclosed binding proteins, glycan refers to the HIV-1 envelope glycoprotein gp120.

[0182] The term T-cell engager refers to binding proteins directed to a host's immune system, more specifically the T cells' cytotoxic activity as well as directed to a HIV target protein.

[0183] The term trimer apex refers to apex of HIV-1 envelope glycoprotein gp120.

[0184] The term monospecific binding protein refers to a binding protein that specifically binds to one antigen target.

[0185] The term monovalent binding protein refers to a binding protein that has one antigen binding site.

[0186] The term bispecific binding protein refers to a binding protein that specifically binds to two different antigen targets.

[0187] The term bivalent binding protein refers to a binding protein that has two binding sites.

[0188] The term trispecific binding protein refers to a binding protein that specifically binds to three different antigen targets.

[0189] The term trivalent binding protein refers to a binding protein that has three binding sites. In particular embodiments the trivalent binding protein can bind to one antigen target. In other embodiments, the trivalent binding protein can bind to two antigen targets. In other embodiments, the trivalent binding protein can bind to three antigen targets.

[0190] An isolated binding protein is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the binding protein, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In some embodiments, the binding protein will be purified: (1) to greater than 95% by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain. Isolated binding proteins include the binding protein in situ, within recombinant cells since at least one component of the binding protein's natural environment will not be present.

[0191] The terms substantially pure or substantially purified as used herein refer to a compound or species that is the predominant species present (i.e., on a molar basis it is more abundant than any other individual species in the composition). In some embodiments, a substantially purified fraction is a composition wherein the species comprises at least about 50% (on a molar basis) of all macromolecular species present. In other embodiments, a substantially pure composition will comprise more than about 80%, 85%, 90%, 95%, or 99% of all macromolar species present in the composition. In still other embodiments, the species is purified to essential homogeneity (contaminant species cannot be detected in the composition by conventional detection methods) wherein the composition consists essentially of a single macromolecular species.

[0192] A neutralizing binding protein as used herein refers to a molecule that is able to block or substantially reduce an effector function of a target antigen to which it binds. As used herein, substantially reduce means at least about 60%, preferably at least about 70%, more preferably at least about 75%, even more preferably at least about 80%, still more preferably at least about 85%, most preferably at least about 90% reduction of an effector function of the target antigen.

[0193] The term epitope includes any determinant, preferably a polypeptide determinant, capable of specifically binding to an immunoglobulin or T-cell receptor. In certain embodiments, epitope determinants include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics and/or specific charge characteristics. An epitope is a region of an antigen that is bound by an antibody or binding protein. In certain embodiments, a binding protein is said to specifically bind an antigen when it preferentially recognizes its target antigen in a complex mixture of proteins and/or macromolecules. In some embodiments, a binding protein is said to specifically bind an antigen when the equilibrium dissociation constant is ?10.sup.?8 M, more preferably when the equilibrium dissociation constant is ?10.sup.?9 M, and most preferably when the dissociation constant is ?10.sup.?10 M.

[0194] The dissociation constant (K.sub.D) of a binding protein can be determined, for example, by surface plasmon resonance. Generally, surface plasmon resonance analysis measures real-time binding interactions between ligand (a target antigen on a biosensor matrix) and analyte (a binding protein in solution) by surface plasmon resonance (SPR) using the BIAcore system (Pharmacia Biosensor; Piscataway, N.J.). Surface plasmon analysis can also be performed by immobilizing the analyte (binding protein on a biosensor matrix) and presenting the ligand (target antigen). The term K.sub.D, as used herein refers to the dissociation constant of the interaction between a particular binding protein and a target antigen.

[0195] The term specifically binds as used herein refers to the ability of a binding protein or an antigen-binding fragment thereof to bind to an antigen containing an epitope with an Kd of at least about 1?10.sup.?6 M, 1?10.sup.?7 M, 1?10.sup.?8 M, 1?10.sup.?9 M, 1?10.sup.?10 M, 1?10.sup.?11 M, 1?10.sup.?12 M, or more, and/or to bind to an epitope with an affinity that is at least two-fold greater than its affinity for a nonspecific antigen.

[0196] The term linker as used herein refers to one or more amino acid residues inserted between immunoglobulin domains to provide sufficient mobility for the domains of the light and heavy chains to fold into cross over dual variable region immunoglobulins. A linker is inserted at the transition between variable domains or between variable and constant domains, respectively, at the sequence level. The transition between domains can be identified because the approximate size of the immunoglobulin domains are well understood. The precise location of a domain transition can be determined by locating peptide stretches that do not form secondary structural elements such as beta-sheets or alpha-helices as demonstrated by experimental data or as can be assumed by techniques of modeling or secondary structure prediction. The linkers described herein are referred to as L.sub.1, which is located on the light chain between the C-terminus of the V.sub.L2 and the N-terminus of the V.sub.L1 domain; and L.sub.2, which is located on the light chain between the C-terminus of the V.sub.L1 and the N-terminus of the C.sub.L domain. The heavy chain linkers are known as L.sub.3, which is located between the C-terminus of the V.sub.H1 and the N-terminus of the V.sub.H2 domain; and L.sub.4, which is located between the C-terminus of the V.sub.H2 and the N-terminus of the C.sub.H1 domain.

[0197] The term vector as used herein refers to any molecule (e.g., nucleic acid, plasmid, or virus) that is used to transfer coding information to a host cell. The term vector includes a nucleic acid molecule that is capable of transporting another nucleic acid to which it has been linked. One type of vector is a plasmid, which refers to a circular double-stranded DNA molecule into which additional DNA segments may be inserted. Another type of vector is a viral vector, wherein additional DNA segments may be inserted into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell and thereby are replicated along with the host genome. In addition, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as recombinant expression vectors (or simply, expression vectors). In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. The terms plasmid and vector may be used interchangeably herein, as a plasmid is the most commonly used form of vector. However, the disclosure is intended to include other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses, and adeno-associated viruses), which serve equivalent functions.

[0198] The phrase recombinant host cell (or host cell) as used herein refers to a cell into which a recombinant expression vector has been introduced. A recombinant host cell or host cell is intended to refer not only to the particular subject cell, but also to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but such cells are still included within the scope of the term host cell as used herein. A wide variety of host cell expression systems can be used to express the binding proteins, including bacterial, yeast, baculoviral, and mammalian expression systems (as well as phage display expression systems). An example of a suitable bacterial expression vector is pUC19. To express a binding protein recombinantly, a host cell is transformed or transfected with one or more recombinant expression vectors carrying DNA fragments encoding the polypeptide chains of the binding protein such that the polypeptide chains are expressed in the host cell and, preferably, secreted into the medium in which the host cells are cultured, from which medium the binding protein can be recovered.

[0199] The term transformation as used herein refers to a change in a cell's genetic characteristics, and a cell has been transformed when it has been modified to contain a new DNA. For example, a cell is transformed where it is genetically modified from its native state. Following transformation, the transforming DNA may recombine with that of the cell by physically integrating into a chromosome of the cell, or may be maintained transiently as an episomal element without being replicated, or may replicate independently as a plasmid. A cell is considered to have been stably transformed when the DNA is replicated with the division of the cell. The term transfection as used herein refers to the uptake of foreign or exogenous DNA by a cell, and a cell has been transfected when the exogenous DNA has been introduced inside the cell membrane. A number of transfection techniques are well known in the art. Such techniques can be used to introduce one or more exogenous DNA molecules into suitable host cells.

[0200] The term naturally occurring as used herein and applied to an object refers to the fact that the object can be found in nature and has not been manipulated by man. For example, a polynucleotide or polypeptide that is present in an organism (including viruses) that can be isolated from a source in nature and that has not been intentionally modified by man is naturally-occurring. Similarly, non-naturally occurring as used herein refers to an object that is not found in nature or that has been structurally modified or synthesized by man.

[0201] As used herein, the twenty conventional amino acids and their abbreviations follow conventional usage. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids; unnatural amino acids and analogs such as ?-,?-disubstituted amino acids, N-alkyl amino acids, lactic acid, and other unconventional amino acids may also be suitable components for the polypeptide chains of the binding proteins. Examples of unconventional amino acids include: 4-hydroxyproline, ?-carboxyglutamate, ?-N,N,N-trimethyllysine, ?-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, ?-N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left-hand direction is the amino terminal direction and the right-hand direction is the carboxyl-terminal direction, in accordance with standard usage and convention.

[0202] Naturally occurring residues may be divided into classes based on common side chain properties:

(1) hydrophobic: Met, Ala, Val, Leu, Ile, Phe, Trp, Tyr, Pro;
(2) polar hydrophilic: Arg, Asn, Asp, Gln, Glu, His, Lys, Ser, Thr;
(3) aliphatic: Ala, Gly, Ile, Leu, Val, Pro;
(4) aliphatic hydrophobic: Ala, Ile, Leu, Val, Pro;
(5) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;
(6) acidic: Asp, Glu;
(7) basic: His, Lys, Arg;
(8) residues that influence chain orientation: Gly, Pro;
(9) aromatic: His, Trp, Tyr, Phe; and
(10) aromatic hydrophobic: Phe, Trp, Tyr.

[0203] Conservative amino acid substitutions may involve exchange of a member of one of these classes with another member of the same class. Non-conservative substitutions may involve the exchange of a member of one of these classes for a member from another class.

[0204] A skilled artisan will be able to determine suitable variants of the polypeptide chains of the binding proteins using well-known techniques. For example, one skilled in the art may identify suitable areas of a polypeptide chain that may be changed without destroying activity by targeting regions not believed to be important for activity. Alternatively, one skilled in the art can identify residues and portions of the molecules that are conserved among similar polypeptides. In addition, even areas that may be important for biological activity or for structure may be subject to conservative amino acid substitutions without destroying the biological activity or without adversely affecting the polypeptide structure.

[0205] The term patient as used herein includes human and animal subjects.

[0206] The terms treatment or treat as used herein refer to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those having the disorder as well as those prone to have a disorder or those in which the disorder is to be prevented. In particular embodiments, binding proteins can be used to treat humans infected with HIV, or humans susceptible to HIV infection, or ameliorate HIV infection in a human subject infected with HIV. The binding proteins can also be used to prevent HIV in a human patient.

[0207] It should be understood as that treating humans infected with HIV include those subjects who are at any one of the several stages of HIV infection progression, which, for example, include acute primary infection syndrome (which can be asymptomatic or associated with an influenza-like illness with fevers, malaise, diarrhea and neurologic symptoms such as headache), asymptomatic infection (which is the long latent period with a gradual decline in the number of circulating CD4.sup.+T cells), and AIDS (which is defined by more serious AIDS-defining illnesses and/or a decline in the circulating CD4 cell count to below a level that is compatible with effective immune function). In addition, treating or preventing HIV infection will also encompass treating suspected infection by HIV after suspected past exposure to HIV by e.g., contact with HIV-contaminated blood, blood transfusion, exchange of body fluids, unsafe sex with an infected person, accidental needle stick, receiving a tattoo or acupuncture with contaminated instruments, or transmission of the virus from a mother to a baby during pregnancy, delivery or shortly thereafter.

[0208] The terms pharmaceutical composition or therapeutic composition as used herein refer to a compound or composition capable of inducing a desired therapeutic effect when properly administered to a patient.

[0209] The term pharmaceutically acceptable carrier or physiologically acceptable carrier as used herein refers to one or more formulation materials suitable for accomplishing or enhancing the delivery of a binding protein.

[0210] The terms effective amount and therapeutically effective amount when used in reference to a pharmaceutical composition comprising one or more binding proteins refer to an amount or dosage sufficient to produce a desired therapeutic result. More specifically, a therapeutically effective amount is an amount of a binding protein sufficient to inhibit, for some period of time, one or more of the clinically defined pathological processes associated with the condition being treated. The effective amount may vary depending on the specific binding protein that is being used, and also depends on a variety of factors and conditions related to the patient being treated and the severity of the disorder. For example, if the binding protein is to be administered in vivo, factors such as the age, weight, and health of the patient as well as dose response curves and toxicity data obtained in preclinical animal work would be among those factors considered. The determination of an effective amount or therapeutically effective amount of a given pharmaceutical composition is well within the ability of those skilled in the art.

[0211] One embodiment of the disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a binding protein.

Trispecific and/or Trivalent Binding Proteins

[0212] In one embodiment, the binding protein of the disclosure is a trispecific and/or trivalent binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., three different) HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0213] In one embodiment, the binding protein of the disclosure is a trispecific and/or trivalent binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., three different) HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0214] In some embodiments, the first polypeptide chain and the second polypeptide chain have a cross-over orientation that forms two distinct antigen binding sites. In some embodiments, the V.sub.H1 and V.sub.L1 form a binding pair and form the first antigen binding site. In some embodiments, the V.sub.H2 and V.sub.L2 form a binding pair and form the second antigen binding site. In some embodiments, the third polypeptide and the fourth polypeptide form a third antigen binding site. In some embodiments, the V.sub.H3 and V.sub.L3 form a binding pair and form the third antigen binding site.

[0215] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; and V.sub.H1, V.sub.H2 and V.sub.H3, are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs:1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242. In other embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-283; and V.sub.H1, V.sub.H2 and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a light chain variable domain comprising a light chain variable domain sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a heavy chain variable domain comprising a heavy chain variable domain sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a light chain variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a heavy chain variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein.

[0216] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; and V.sub.H1, V.sub.H2 and V.sub.H3, are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472. In other embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and V.sub.H1, V.sub.H2 and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487.

[0217] In particular embodiments, the order of the V.sub.H1 and V.sub.H2 domains, and therefore the order of V.sub.L1 and V.sub.L2 domains, in the polypeptide chain of formula I or the polypeptide chain of formula II (i.e., to reverse the order) are swapped.

[0218] In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.

[0219] In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 9; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10.

[0220] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 20; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 19; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18.

[0221] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 28 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 28; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 27 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 27; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 25 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 25; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 26 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 26.

[0222] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34.

[0223] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 44; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 43 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 43; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 41; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 42.

[0224] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 52 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 52; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 51 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 49 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 49; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 50.

[0225] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 60 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 60; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 59 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 59; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 57 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 57; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 58.

[0226] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66.

[0227] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74.

[0228] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 84; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82.

[0229] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:92; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90.

[0230] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98.

[0231] In other embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106.

[0232] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114.

[0233] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122.

[0234] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130.

[0235] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138.

[0236] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146.

[0237] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154.

[0238] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162.

[0239] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170.

[0240] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 180 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 180; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 179 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 179; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 177 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 177; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 178 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178.

[0241] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 188 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 188; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 187 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 187; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 185 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 185; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 186 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 186.

[0242] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 196 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 196; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 195 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 195; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 193 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 194 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 194.

[0243] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 204 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 204; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 203 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 201 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 202 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202.

[0244] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 212; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 211 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 211; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 209 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 209; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 210 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 210.

[0245] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 220 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 219 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 219; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 217 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 217; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 218 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 218.

[0246] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 228 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 228; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 227 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 227; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 225 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 225; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 226 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 226.

[0247] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 235 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 234 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 234; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 232 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 232; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 233 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233.

[0248] In other embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 243 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 242 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 242; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 240 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 240; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 241 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241.

[0249] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 305 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 305; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 304 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 302 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 302; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 303 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303.

[0250] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 313 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 313; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 312 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 312; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 310 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 310; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 311 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 311.

[0251] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 321 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 321; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 320 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 320; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 318 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 318; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 319 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319.

[0252] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 329 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 329; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 328 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 328; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 326 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 326; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 327 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 327.

[0253] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 337 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 336 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 336; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 334 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 334; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 335 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 335.

[0254] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 345 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 345; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 344 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 344; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 342 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 342; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 343 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 343.

[0255] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 353 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 353; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:352; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 350 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 350; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 351 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 351.

[0256] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 361 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 361; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 360 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 360; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 358 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 358; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 359 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 359.

[0257] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 369 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 369; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 368 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 368; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 366 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 366; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 367 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 367.

[0258] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 377 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 377; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 376 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 376; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 374 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 374; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 375 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 375.

[0259] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 385 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 385; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 384 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 384; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 382 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 382; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 383 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 383.

[0260] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 393 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 393; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 392 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 392; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 390 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 390; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 391 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 391.

[0261] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 401 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 401; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 400 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 400; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 398 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 398; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 399 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 399.

[0262] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 409 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 409; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 408 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 408; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 406 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 407 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 407.

[0263] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 417 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 417; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 416 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 416; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 414 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 414; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 415 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 415.

[0264] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 425 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 425; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 424 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 424; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 422 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 422; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 423 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 423.

[0265] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 433 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:433; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 432 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 432; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 430 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 430; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 431 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 431.

[0266] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 441 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 441; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 440 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 438 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 438; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 439 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439.

[0267] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 449 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 449; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 448 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 448; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 446 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 446; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 447 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 447.

[0268] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 457 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 457; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 456 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 456; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 454 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 454; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 455 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 455.

[0269] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 465 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 465; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 464 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 464; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 462 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 462; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 463 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 463.

[0270] In another embodiment, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 473 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 473; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 472 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 472; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 470 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 470; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 471 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 471.

[0271] In other embodiments, the binding protein of the disclosure is a trispecific and/or trivalent binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., three) HIV target antigens, wherein a first polypeptide chain has a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain has a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3(hole)[II]

and a third polypeptide chain has a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3(knob)[III]

and a fourth polypeptide chain has a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0272] In other embodiments, the binding protein of the disclosure is a trispecific and/or trivalent binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., three) HIV target antigens, wherein a first polypeptide chain has a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain has a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3(knob)[II]

and a third polypeptide chain has a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3(hole)[III]

and a fourth polypeptide chain has a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

Additional Examples of Trispecific Binding Proteins

[0273] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising an amino acid sequence having at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to a sequence as set forth in any one of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0274] In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising an amino acid sequence having at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to a sequence as set forth in any one of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0275] In some embodiments, V.sub.L1, V.sub.L2, and V.sub.L3 comprise an amino acid sequence as set forth in SEQ ID NOs: 518, 519, and 512, respectively, and V.sub.H1, V.sub.H2, and V.sub.H3 comprise an amino acid sequence as set forth in SEQ ID NOs: 504, 506, and 502, respectively. In some embodiments, V.sub.L1, V.sub.L2, and V.sub.L3 comprise an amino acid sequence as set forth in SEQ ID NOs: 518, 519, and 513, respectively, and V.sub.H1, V.sub.H2, and V.sub.H3 comprises an amino acid sequence as set forth in SEQ ID NOs: 504, 506, and 503, respectively. In some embodiments, V.sub.L1, V.sub.L2, and V.sub.L3 comprises an amino acid sequence as set forth in SEQ ID NOs: 519, 518, and 513, respectively, and V.sub.H1, V.sub.H2, and V.sub.H3 comprises an amino acid sequence as set forth in SEQ ID NOs: 506, 504, and 503, respectively.

[0276] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a light chain variable domain sequence shown in Table C. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a heavy chain variable domain sequence shown in Table C.

[0277] In some embodiments, V.sub.L1 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 518, V.sub.L2 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 519, V.sub.L3 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 512, V.sub.H1 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 504, V.sub.H2 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 506, and V.sub.H3 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 502. In some embodiments, V.sub.L1 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 518, V.sub.L2 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 519, V.sub.L3 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 513, V.sub.H1 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 504, V.sub.H, is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 506, and V.sub.H3 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 503. In some embodiments. V.sub.L1 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 519, V.sub.L2 is a variable domain comprising a CDR-L1. CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 518, V.sub.L3 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 513, and V.sub.H1 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 506, V.sub.H2 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 504, and V.sub.H3 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 503.

[0278] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising: (a) a CDR-L1 comprising a sequence selected from the group consisting of SEQ ID NOs: 266, 269, 275, 278, 281, and 500; (b) a CDR-L2 comprising a sequence selected from the group consisting of SEQ ID NOs: 267, 270, 276, 279, 282, and 501; and/or (c) a CDR-L3 comprising a sequence selected from the group consisting of SEQ ID NOs: 268, 271, 274, 277, 280, and 283. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences as shown in Table B. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

[0279] In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising: (a) a CDR-H1 comprising a sequence selected from the group consisting of SEQ ID NOs: 248, 251, 254, 257, 263, and 499; (b) a CDR-H2 comprising a sequence selected from the group consisting of SEQ ID NOs: 252, 255, 258, 261, 264, and 497; and/or (c) a CDR-H3 comprising a sequence selected from the group consisting of SEQ ID NOs: 250, 253, 256, 259, 262, 265, and 498. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences as shown in Table B. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

[0280] In some embodiments, V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 500, 501, and 274, respectively; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 275, 276, and 277, respectively; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 266, 267, and 268, respectively; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 254, 255, and 256, respectively; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 257, 258, and 259, respectively; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 248, 497, and 250, respectively. In some embodiments, V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 500, 501, and 274, respectively; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 275, 276, and 277, respectively; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 269, 270, and 271, respectively; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 254, 255, and 256, respectively; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 257, 258, and 259, respectively; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 251, 252, and 253, respectively. In some embodiments, V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 275, 276, and 277, respectively; V.sub.2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 500, 501, and 274, respectively; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 269, 270, and 271, respectively; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 257, 258, and 259, respectively; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 254, 255, and 256, respectively; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 251, 252, and 253, respectively.

[0281] Additional Trispecific Binding Proteins Targeting One or More HIV Target Proteins and One or More T Cell Target Proteins

[0282] In some embodiments, a binding protein of the present disclosure comprises four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., one or two) HIV target proteins and one or more (e.g., one or two) T cell target proteins, wherein a first polypeptide chain has a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I];

a second polypeptide chain has a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II];

a third polypeptide chain has a structure represented by the formula:

V.sub.H3-C.sub.H1[III];

and a fourth polypeptide chain has a structure represented by the formula:

V.sub.L3-C.sub.L[IV];

wherein
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0283] In some embodiments, a binding protein of the present disclosure comprises four polypeptide chains that form three antigen binding sites that specifically bind one or more (e.g., one or two) HIV target proteins and one or more (e.g., one or two) T cell target proteins, wherein a first polypeptide chain has a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I];

a second polypeptide chain has a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II];

a third polypeptide chain has a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III];

and a fourth polypeptide chain has a structure represented by the formula

V.sub.L3-C.sub.L[IV];

wherein
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0284] In some embodiments, the first polypeptide chain and the second polypeptide chain have a cross-over orientation that forms two distinct antigen binding sites. In some embodiments, the V.sub.H1 and V.sub.L1 form a binding pair and form the first antigen binding site. In some embodiments, the V.sub.H2 and V.sub.L2 form a binding pair and form the second antigen binding site. In some embodiments, the third polypeptide and the fourth polypeptide form a third antigen binding site. In some embodiments, the V.sub.H3 and V.sub.L3 form a binding pair and form the third antigen binding site.

[0285] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising an amino acid sequence having at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%/0, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to a sequence as set forth in any one of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0286] In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising an amino acid sequence having at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 990% sequence identity to a sequence as set forth in any one of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0287] In some embodiments, V.sub.L1, V.sub.L2, and V.sub.L3 comprise an amino acid sequence as set forth in SEQ ID NOs: 522, 524, and 513, respectively, and V.sub.H1, V.sub.H2, and V.sub.H3 comprise an amino acid sequence as set forth in SEQ ID NOs: 509, 511, and 503, respectively. In some embodiments, V.sub.L1, V.sub.L2, and V.sub.L3 comprise an amino acid sequence as set forth in SEQ ID NOs: 524, 522, and 513, respectively, and V.sub.H1, V.sub.H2, and V.sub.H3 comprise an amino acid sequence as set forth in SEQ ID NOs: 511, 509, and 503, respectively.

[0288] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0289] In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0290] In some embodiments, V.sub.L1 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 522, V.sub.L2 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 524, V.sub.L3 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 513, V.sub.H1 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 509, V.sub.H2 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 511, and V.sub.H3 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 503. In some embodiments, V.sub.L1 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 524, V.sub.L2 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence of SEQ ID NO: 522, V.sub.L3 is a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a light chain variable domain sequence of SEQ ID NO: 513, V.sub.H1 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 511, V.sub.H2 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 509, and V.sub.H3 is a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence of SEQ ID NO: 503.

[0291] In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising: (a) a CDR-L1 comprising a sequence selected from the group consisting of SEQ ID NOs: 266, 269, 275, 278, 281, 488, 491, 494 and 500; (b) a CDR-L2 comprising a sequence selected from the group consisting of SEQ ID NOs: 267, 270, 276, 279, 282, 489, 492, 495, and 501; and (c) a CDR-L3 comprising a sequence selected from the group consisting of SEQ ID NOs: 268, 271, 274, 277, 280, 283, 490, 493, and 496. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences as shown in Table B. In some embodiments, V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain comprising a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

[0292] In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising: (a) a CDR-H1 comprising a sequence selected from the group consisting of SEQ ID NOs: 248, 251, 254, 257, 263, 479, 482, 485, and 499; (b) a CDR-H2 comprising a sequence selected from the group consisting of SEQ ID NOs: 252, 255, 258, 261, 264, 480, 483, 486, and 497; and (c) a CDR-H3 comprising a sequence selected from the group consisting of SEQ ID NOs: 250, 253, 256, 259, 262, 265, 481, 484, 487, and 498. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences as shown in Table B. In some embodiments, V.sub.H1, V.sub.H2 and V.sub.H3 are each independently a variable domain comprising a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

[0293] In some embodiments, V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 488, 489, and 490, respectively; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 494, 495, and 496, respectively; V.sub.L3 comprises a CDR-L1. CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 269, 270, and 271, respectively; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 479, 480, and 481, respectively; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 485, 486, and 487, respectively; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 251, 252, and 253, respectively. In some embodiments, V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 494, 495, and 496, respectively; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 488, 489, and 490, respectively; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the sequence of SEQ ID NOs: 269, 270, and 271, respectively; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 485, 486, and 487, respectively; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 479, 480, and 481, respectively; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the sequence of SEQ ID NOs: 251, 252, and 253, respectively.

[0294] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein.

[0295] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 described herein.

[0296] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein.

[0297] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein.

[0298] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 described herein.

[0299] In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD3 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising a light and heavy chain variable sequence of antibody CD28 or CD28_2 described herein. In some embodiments, V.sub.L1 and V.sub.H1 are light and heavy chain variable domains comprising the six CDRs of antibody CD4BS a, CD4BS b, MPER, MPER_100W, V1/V2 directed a, V1/V2 directed b, or V3 directed described herein, V.sub.L2 and V.sub.H2 are light and heavy chain variable domains comprising the six CDRs of antibody CD3 or CD28_2 described herein, and V.sub.L3 and V.sub.H3 are light and heavy chain variable domains comprising the six CDRs of antibody CD28 or CD28_2 described herein.

[0300] Target Proteins

[0301] In one embodiment, the binding proteins specifically bind to one or more HIV target proteins. In some embodiments, the binding proteins are trispecific and specifically bind to MPER of the HIV-1 gp41 protein, a CD4 binding site of the HIV-1 gp120 protein, a glycan in the V3 loop of the HIV-1 gp120 protein, a trimer apex of the HIV-1 gp120 protein or gp160. In other embodiments, the binding proteins specifically bind to one or more HIV target proteins and one or more target proteins on a T-cell including T cell receptor complex. These T-cell engager binding proteins are capable of recruiting T cells transiently to target cells and, at the same time, activating the cytolytic activity of the T cells. The T-cell engager trispecific antibodies can be used to activate HIV-1 reservoirs and redirect/activate T cells to lyse latently infected HIV-1.sup.+ T cells. Examples of target proteins on T cells include but are not limited to CD3 and CD28, among others. In some embodiments, the trispecific binding proteins may be generated by combining the antigen binding domains of two or more monospecific antibodies (parent antibodies) into one antibody. See International Publication Nos. WO 2011/038290 A2, WO 2013/086533 A1, WO 2013/070776 A1, WO 2012/154312 A1, and WO 2013/163427 A1, which are hereby incorporated into this disclosure by reference. The binding proteins of the disclosure may be prepared using domains or sequences obtained or derived from any human or non-human antibody, including, for example, human, murine, or humanized antibodies.

[0302] In some embodiments of the disclosure, the trivalent binding protein is capable of binding three different antigen targets. In one embodiment, the binding protein is trispecific and one light chain-heavy chain pair is capable of binding two different antigen targets or epitopes and one light chain-heavy chain pair is capable of binding one antigen target or epitope. In another embodiment, the binding protein is capable of binding three different HIV antigen targets that are located on the HIV envelope glycoprotein structure composed of gp120 and gp41 subunits. In other embodiments, the binding protein is capable of inhibiting the function of one or more of the antigen targets.

[0303] In some embodiments, a binding protein of the present disclosure binds one or more HIV target proteins. In some embodiments, the binding protein is capable of specifically binding three different epitopes on a single HIV target protein. In some embodiments, the binding protein is capable of binding two different epitopes on a first HIV target protein, and one epitope on a second HIV target protein. In some embodiments, the first and second HIV target proteins are different. In some embodiments, the binding protein is capable of specifically binding three different HIV target protein. In some embodiments, the one or more HIV target proteins are one or more of glycoprotein 120, glycoprotein 41, and glycoprotein 160.

[0304] In some embodiments, a binding protein of the present disclosure binds one or more HIV target proteins and one or more T cell target proteins. In some embodiments, the binding protein is capable of specifically binding one HIV target protein and two different epitopes on a single T cell target protein. In some embodiments, the binding protein is capable of specifically binding one HIV target protein and two different T cell target proteins (e.g., CD28 and CD3). In some embodiments, the binding protein is capable of specifically binding one T cell target protein and two different epitopes on a single HIV target protein. In some embodiments, the binding protein is capable of specifically binding one T cell target protein and two different HIV target proteins. In some embodiments, the first and second polypeptide chains of the binding protein form two antigen binding sites that specifically target two T cell target proteins, and the third and fourth polypeptide chains of the binding protein form an antigen binding site that specifically binds an HIV target protein. In some embodiments, the one or more HIV target proteins are one or more of glycoprotein 120, glycoprotein 41, and glycoprotein 160. In some embodiments, the one or more T cell target proteins are one or more of CD3 and CD28.

[0305] Linkers

[0306] In some embodiments, the linkers L.sub.1, L.sub.2, L.sub.3, and L.sub.4 range from no amino acids (length=0) to about 100 amino acids long, or less than 100, 50, 40, 30, 20, or 15 amino acids or less. The linkers can also be 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acids long. L.sub.1, L.sub.2, L.sub.3, and L.sub.4 in one binding protein may all have the same amino acid sequence or may all have different amino acid sequences.

[0307] Examples of suitable linkers include a single glycine (Gly) residue; a diglycine peptide (Gly-Gly); a tripeptide (Gly-Gly-Gly); a peptide with four glycine residues (Gly-Gly-Gly-Gly; SEQ ID NO: 285); a peptide with five glycine residues (Gly-Gly-Gly-Gly-Gly; SEQ ID NO: 286); a peptide with six glycine residues (Gly-Gly-Gly-Gly-Gly-Gly; SEQ ID NO: 287); a peptide with seven glycine residues (Gly-Gly-Gly-Gly-Gly-Gly-Gly; SEQ ID NO: 288); a peptide with eight glycine residues (Gly-Gly-Gly-Gly-Gly-Gly-Gly-Gly; SEQ ID NO: 289). Other combinations of amino acid residues may be used such as the peptide Gly-Gly-Gly-Gly-Ser (SEQ ID NO: 290), the peptide Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser (SEQ ID NO: 291) and the peptide Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser (SEQ ID NO: 292). Other suitable linkers include a single Ser, and Val residue; the dipeptide Arg-Thr, Gln-Pro, Ser-Ser, Thr-Lys, and Ser-Leu; Thr-Lys-Gly-Pro-Ser (SEQ ID NO: 293), Thr-Val-Ala-Ala-Pro (SEQ ID NO: 294), Gln-Pro-Lys-Ala-Ala (SEQ ID NO: 295), Gln-Arg-Ile-Glu-Gly (SEQ ID NO: 296); Ala-Ser-Thr-Lys-Gly-Pro-Ser (SEQ ID NO: 297), Arg-Thr-Val-Ala-Ala-Pro-Ser (SEQ ID NO: 298), Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299), and His-Ile-Asp-Ser-Pro-Asn-Lys (SEQ ID NO: 300). The examples listed above are not intended to limit the scope of the disclosure in any way, and linkers comprising randomly selected amino acids selected from the group consisting of valine, leucine, isoleucine, serine, threonine, lysine, arginine, histidine, aspartate, glutamate, asparagine, glutamine, glycine, and proline have been shown to be suitable in the binding proteins.

[0308] The identity and sequence of amino acid residues in the linker may vary depending on the type of secondary structural element necessary to achieve in the linker. For example, glycine, serine, and alanine are best for linkers having maximum flexibility. Some combination of glycine, proline, threonine, and serine are useful if a more rigid and extended linker is necessary. Any amino acid residue may be considered as a linker in combination with other amino acid residues to construct larger peptide linkers as necessary depending on the desired properties.

[0309] In some embodiments, the length of L.sub.1 is at least twice the length of L.sub.3. In some embodiments, the length of L.sub.2 is at least twice the length of L.sub.4. In some embodiments, the length of L.sub.1 is at least twice the length of L.sub.3, and the length of L.sub.2 is at least twice the length of L.sub.4. In some embodiments, L.sub.1 is 3 to 12 amino acid residues in length, L.sub.2 is 3 to 14 amino acid residues in length, L.sub.3 is 1 to 8 amino acid residues in length, and L.sub.4 is 1 to 3 amino acid residues in length. In some embodiments, L.sub.1 is 5 to 10 amino acid residues in length, L.sub.2 is 5 to 8 amino acid residues in length, L.sub.3 is 1 to 5 amino acid residues in length, and L.sub.4 is 1 to 2 amino acid residues in length. In some embodiments, L.sub.1 is 7 amino acid residues in length, L.sub.2 is 5 amino acid residues in length, L.sub.3 is 1 amino acid residue in length, and L.sub.4 is 2 amino acid residues in length.

[0310] In some embodiments, L.sub.1, L.sub.2, L.sub.3, and/or L.sub.4 comprise the sequence Asp-Lys-Thr-His-Thr (SEQ ID NO: 525). In some embodiments, L.sub.1 comprises the sequence Asp-Lys-Thr-His-Thr (SEQ ID NO: 525). In some embodiments, L.sub.3 comprises the sequence Asp-Lys-Thr-His-Thr (SEQ ID NO: 525).

[0311] In some embodiments, L.sub.1, L.sub.2, L.sub.3, and/or L.sub.4 comprise the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299). In some embodiments, L.sub.1 comprises the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299). In some embodiments, L.sub.1 comprises the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299), L.sub.2 comprises the sequence Thr-Lys-Gly-Pro-Ser-Arg (SEQ ID NO: 526), L.sub.3 comprises the sequence Ser, and L.sub.4 comprises the sequence Arg-Thr. In some embodiments, L.sub.3 comprises the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299). In some embodiments, L.sub.1 comprises the sequence Ser, L.sub.2 comprises the sequence Arg-Thr, L.sub.3 comprises the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299) and L.sub.4 comprises the sequence Thr-Lys-Gly-Pro-Ser-Arg (SEQ ID NO: 526).

[0312] Fc Regions and Constant Domains

[0313] In some embodiments, a binding protein of the present disclosure comprises a second polypeptide chain further comprising an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains. In some embodiments, a binding protein of the present disclosure comprises a third polypeptide chain further comprising an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains. In some embodiments, a binding protein of the present disclosure comprises a second polypeptide chain further comprising an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and a third polypeptide chain further comprising an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0314] To improve the yields of the binding proteins, in some embodiments, the C.sub.H3 domains can be altered by the knob-into-holes technology which is described in detail with several examples in, for example, International Publication No. WO 96/027011, Ridgway et al., 1996, Protein Eng. 9: 617-21; and Merchant et al., 1998, Nat. Biotechnol. 16: 677-81. Specifically, the interaction surfaces of the two C.sub.H3 domains are altered to increase the heterodimerisation of both heavy chains containing these two C.sub.H3 domains. Each of the two C.sub.H3 domains (of the two heavy chains) can be the knob, while the other is the hole. The introduction of a disulfide bridge further stabilizes the heterodimers (Merchant et al., 1998; Atwell et al., 1997, J. Mol. Biol. 270: 26-35) and increases the yield. In particular embodiments, the knob is on the second pair of polypeptides with a single variable domain. In other embodiments, the knob is on the first pair of polypeptides having the cross-over orientation. In yet other embodiments, the C.sub.H3 domains do not include a knob in hole.

[0315] In some embodiments, a binding protein of the present disclosure comprises a knob mutation on the second polypeptide chain and a hole mutation on the third polypeptide chain. In some embodiments, a binding protein of the present disclosure comprises a knob mutation on the third polypeptide chain and a hole mutation on the second polypeptide chain. In some embodiments, the knob mutation comprises substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index. In some embodiments, the amino acid substitutions are S354C and T366W. In some embodiments, the hole mutation comprises substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index. In some embodiments, the amino acid substitutions are Y349C, T366S, L368A, and Y407V. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0316] In some embodiments, a binding protein of the present disclosure comprises one or more mutations to improve serum half-life (See e.g., Hinton, P. R. et al. (2006) J. Immunol. 176(1):346-56). In some embodiments, the mutation comprises substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. In some embodiments, the binding protein comprises a second polypeptide chain further comprising a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and a third polypeptide chain further comprising a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. In some embodiments, a binding protein of the present disclosure comprises knob and hole mutations and one or more mutations to improve serum half-life.

[0317] In some embodiments, C.sub.H1, C.sub.H2, C.sub.H3 and C.sub.L of the trispecific binding proteins described herein may comprise any of C.sub.H1, C.sub.H2, C.sub.H3 and C.sub.L sequences of binding proteins 1-53.

[0318] Nucleic Acids

[0319] Standard recombinant DNA methodologies are used to construct the polynucleotides that encode the polypeptides which form the binding proteins, incorporate these polynucleotides into recombinant expression vectors, and introduce such vectors into host cells. See e.g., Sambrook et al., 2001, MOLECULAR CLONING: A LABORATORY MANUAL (Cold Spring Harbor Laboratory Press, 3rd ed.). Enzymatic reactions and purification techniques may be performed according to manufacturer's specifications, as commonly accomplished in the art, or as described herein. Unless specific definitions are provided, the nomenclature utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Similarly, conventional techniques may be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, delivery, and treatment of patients.

[0320] Other aspects of the present disclosure relate to isolated nucleic acid molecules comprising a nucleotide sequence encoding any of the binding proteins described herein. In some embodiments, the isolated nucleic acid is operably linked to a heterologous promoter to direct transcription of the binding protein-coding nucleic acid sequence. A promoter may refer to nucleic acid control sequences which direct transcription of a nucleic acid. A first nucleic acid sequence is operably linked to a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence of a binding protein if the promoter affects the transcription or expression of the coding sequence. Examples of promoters may include, but are not limited to, promoters obtained from the genomes of viruses (such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus, Simian Virus 40 (SV40), and the like), from heterologous eukaryotic promoters (such as the actin promoter, an immunoglobulin promoter, from heat-shock promoters, and the like), the CAG-promoter (Niwa et al., Gene 108(2): 193-9, 1991), the phosphoglycerate kinase (PGK)-promoter, a tetracycline-inducible promoter (Masui et al., Nucleic Acids Res. 33:e43, 2005), the lac system, the trp system, the tac system, the trc system, major operator and promoter regions of phage lambda, the promoter for 3-phosphoglycerate kinase, the promoters of yeast acid phosphatase, and the promoter of the yeast alpha-mating factors. Polynucleotides encoding binding proteins of the present disclosure may be under the control of a constitutive promoter, an inducible promoter, or any other suitable promoter described herein or other suitable promoter that will be readily recognized by one skilled in the art.

[0321] In some embodiments, the isolated nucleic acid is incorporated into a vector. In some embodiments, the vector is an expression vector. Expression vectors may include one or more regulatory sequences operatively linked to the polynucleotide to be expressed. The term regulatory sequence includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Examples of suitable enhancers may include, but are not limited to, enhancer sequences from mammalian genes (such as globin, elastase, albumin, ?-fetoprotein, insulin and the like), and enhancer sequences from a eukaryotic cell virus (such as SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, adenovirus enhancers, and the like). Examples of suitable vectors may include, for example, plasmids, cosmids, episomes, transposons, and viral vectors (e.g., adenoviral, vaccinia viral, Sindbis-viral, measles, herpes viral, lentiviral, retroviral, adeno-associated viral vectors, etc.). Expression vectors can be used to transfect host cells, such as, for example, bacterial cells, yeast cells, insect cells, and mammalian cells. Biologically functional viral and plasmid DNA vectors capable of expression and replication in a host are known in the art, and can be used to transfect any cell of interest.

[0322] Other aspects of the present disclosure relate to a vector system comprising one or more vectors encoding a first, second, third, and fourth polypeptide chain of any of the binding proteins described herein. In some embodiments, the vector system comprises a first vector encoding the first polypeptide chain of the binding protein, a second vector encoding the second polypeptide chain of the binding protein, a third vector encoding the third polypeptide chain of the binding protein, and a fourth vector encoding the fourth polypeptide chain of the binding protein. In some embodiments, the vector system comprises a first vector encoding the first and second polypeptide chains of the binding protein, and a second vector encoding the third and fourth polypeptide chains of the binding protein. In some embodiments, the vector system comprises a first vector encoding the first and third polypeptide chains of the binding protein, and a second vector encoding the second and fourth polypeptide chains of the binding protein. In some embodiments, the vector system comprises a first vector encoding the first and fourth polypeptide chains of the binding protein, and a second vector encoding the second and third polypeptide chains of the binding protein. In some embodiments, the vector system comprises a first vector encoding the first, second, third, and fourth polypeptide chains of the binding protein. The one or more vectors of the vector system may be any of the vectors described herein. In some embodiments, the one or more vectors are expression vectors.

[0323] Host Cells

[0324] Other aspects of the present disclosure relate to a host cell (e.g., an isolated host cell) comprising one or more isolated polynucleotides, vectors, and/or vector systems described herein. In some embodiments, an isolated host cell of the present disclosure is cultured in vitro. In some embodiments, the host cell is a bacterial cell (e.g., an E. coli cell). In some embodiments, the host cell is a yeast cell (e.g., an S. cerevisiae cell). In some embodiments, the host cell is an insect cell. Examples of insect host cells may include, for example, Drosophila cells (e.g., S2 cells), Trichoplusia ni cells (e.g., High Five? cells), and Spodoptera frugiperda cells (e.g., Sf21 or Sf9 cells). In some embodiments, the host cell is a mammalian cell. Examples of mammalian host cells may include, for example, human embryonic kidney cells (e.g., 293 or 293 cells subcloned for growth in suspension culture), Expi293? cells, CHO cells, baby hamster kidney cells (e.g., BHK, ATCC CCL 10), mouse sertoli cells (e.g., TM4 cells), monkey kidney cells (e.g., CV1 ATCC CCL 70), African green monkey kidney cells (e.g., VERO-76, ATCC CRL-1587), human cervical carcinoma cells (e.g., HELA, ATCC CCL 2), canine kidney cells (e.g., MDCK, ATCC CCL 34), buffalo rat liver cells (e.g., BRL 3A, ATCC CRL 1442), human lung cells (e.g., W138, ATCC CCL 75), human liver cells (e.g., Hep G2, HB 8065), mouse mammary tumor cells (e.g., MMT 060562, ATCC CCL51), TRI cells, MRC 5 cells, FS4 cells, a human hepatoma line (e.g., Hep G2), and myeloma cells (e.g., NS0 and Sp2/0 cells).

[0325] Other aspects of the present disclosure relate to a method of producing any of the binding proteins described herein. In some embodiments, the method includes a) culturing a host cell (e.g., any of the host cells described herein) comprising an isolated nucleic acid, vector, and/or vector system (e.g., any of the isolated nucleic acids, vectors, and/or vector systems described herein) under conditions such that the host cell expresses the binding protein; and b) isolating the binding protein from the host cell. Methods of culturing host cells under conditions to express a protein are well known to one of ordinary skill in the art. Methods of isolating proteins from cultured host cells are well known to one of ordinary skill in the art, including, for example, by affinity chromatography (e.g., two step affinity chromatography comprising protein A affinity chromatography followed by size exclusion chromatography).

Use for Binding Proteins

[0326] The binding proteins can be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays for the detection and quantitation of one or more target antigens. The binding proteins will bind the one or more target antigens with an affinity that is appropriate for the assay method being employed.

[0327] For diagnostic applications, in certain embodiments, binding proteins can be labeled with a detectable moiety. The detectable moiety can be any one that is capable of producing, either directly or indirectly, a detectable signal. For example, the detectable moiety can be a radioisotope, such as .sup.3H, .sup.14C, .sup.32P, .sup.35S, .sup.125I, .sup.99Tc, .sup.111In, or .sup.67Ga; a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin; or an enzyme, such as alkaline phosphatase, ?-galactosidase, or horseradish peroxidase.

[0328] The binding proteins are also useful for in vivo imaging. A binding protein labeled with a detectable moiety can be administered to an animal, e.g., into the bloodstream, and the presence and location of the labeled antibody in the host assayed. The binding protein can be labeled with any moiety that is detectable in an animal, whether by nuclear magnetic resonance, radiology, or other detection means known in the art.

[0329] The disclosure also relates to a kit comprising a binding protein and other reagents useful for detecting target antigen levels in biological samples. Such reagents can include a detectable label, blocking serum, positive and negative control samples, and detection reagents. In some embodiments, the kit comprises a composition comprising any binding protein, polynucleotide, vector, vector system, and/or host cell described herein. In some embodiments, the kit comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition which is by itself or combined with another composition effective for treating, preventing and/or diagnosing a condition (e.g., HIV infection) and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). In some embodiments, the label or package insert indicates that the composition is used for preventing, diagnosing, and/or treating the condition of choice. Alternatively, or additionally, the article of manufacture or kit may further comprise a second (or third) container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

[0330] Therapeutic or pharmaceutical compositions comprising binding proteins are within the scope of the disclosure. Such therapeutic or pharmaceutical compositions can comprise a therapeutically effective amount of a binding protein, or binding protein-drug conjugate, in admixture with a pharmaceutically or physiologically acceptable formulation agent selected for suitability with the mode of administration.

[0331] Acceptable formulation materials are nontoxic to recipients at the dosages and concentrations employed.

[0332] The pharmaceutical composition can contain formulation materials for modifying, maintaining, or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration of the composition. Suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine, or lysine), antimicrobials, antioxidants (such as ascorbic acid, sodium sulfite, or sodium hydrogen-sulfite), buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates, or other organic acids), bulking agents (such as mannitol or glycine), chelating agents (such as ethylenediamine tetraacetic acid (EDTA)), complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin, or hydroxypropyl-beta-cyclodextrin), fillers, monosaccharides, disaccharides, and other carbohydrates (such as glucose, mannose, or dextrins), proteins (such as serum albumin, gelatin, or immunoglobulins), coloring, flavoring and diluting agents, emulsifying agents, hydrophilic polymers (such as polyvinylpyrrolidone), low molecular weight polypeptides, salt-forming counterions (such as sodium), preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid, or hydrogen peroxide), solvents (such as glycerin, propylene glycol, or polyethylene glycol), sugar alcohols (such as mannitol or sorbitol), suspending agents, surfactants or wetting agents (such as pluronics; PEG; sorbitan esters; polysorbates such as polysorbate 20 or polysorbate 80; triton; tromethamine; lecithin; cholesterol or tyloxapal), stability enhancing agents (such as sucrose or sorbitol), tonicity enhancing agents (such as alkali metal halidese.g., sodium or potassium chlorideor mannitol sorbitol), delivery vehicles, diluents, excipients and/or pharmaceutical adjuvants (see, e.g., REMINGTON'S PHARMACEUTICAL SCIENCES (18th Ed., A. R. Gennaro, ed., Mack Publishing Company 1990), and subsequent editions of the same, incorporated herein by reference for any purpose).

[0333] The optimal pharmaceutical composition will be determined by a skilled artisan depending upon, for example, the intended route of administration, delivery format, and desired dosage. Such compositions can influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the binding protein.

[0334] The primary vehicle or carrier in a pharmaceutical composition can be either aqueous or non-aqueous in nature. For example, a suitable vehicle or carrier for injection can be water, physiological saline solution, or artificial cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. Other exemplary pharmaceutical compositions comprise Tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, which can further include sorbitol or a suitable substitute. In one embodiment of the disclosure, binding protein compositions can be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents in the form of a lyophilized cake or an aqueous solution. Further, the binding protein can be formulated as a lyophilizate using appropriate excipients such as sucrose.

[0335] The pharmaceutical compositions of the disclosure can be selected for parenteral delivery or subcutaneous. Alternatively, the compositions can be selected for inhalation or for delivery through the digestive tract, such as orally. The preparation of such pharmaceutically acceptable compositions is within the skill of the art.

[0336] The formulation components are present in concentrations that are acceptable to the site of administration. For example, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8.

[0337] When parenteral administration is contemplated, the therapeutic compositions for use can be in the form of a pyrogen-free, parenterally acceptable, aqueous solution comprising the desired binding protein in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is sterile distilled water in which a binding protein is formulated as a sterile, isotonic solution, properly preserved. Yet another preparation can involve the formulation of the desired molecule with an agent, such as injectable microspheres, bio-erodible particles, polymeric compounds (such as polylactic acid or polyglycolic acid), beads, or liposomes, that provides for the controlled or sustained release of the product which can then be delivered via a depot injection. Hyaluronic acid can also be used, and this can have the effect of promoting sustained duration in the circulation. Other suitable means for the introduction of the desired molecule include implantable drug delivery devices.

[0338] In one embodiment, a pharmaceutical composition can be formulated for inhalation. For example, a binding protein can be formulated as a dry powder for inhalation. Binding protein inhalation solutions can also be formulated with a propellant for aerosol delivery. In yet another embodiment, solutions can be nebulized.

[0339] It is also contemplated that certain formulations can be administered orally. In one embodiment of the disclosure, binding proteins that are administered in this fashion can be formulated with or without those carriers customarily used in the compounding of solid dosage forms such as tablets and capsules. For example, a capsule can be designed to release the active portion of the formulation at the point in the gastrointestinal tract where bioavailability is maximized and pre-systemic degradation is minimized. Additional agents can be included to facilitate absorption of the binding protein. Diluents, flavorings, low melting point waxes, vegetable oils, lubricants, suspending agents, tablet disintegrating agents, and binders can also be employed.

[0340] Another pharmaceutical composition can involve an effective quantity of binding proteins in a mixture with non-toxic excipients that are suitable for the manufacture of tablets. By dissolving the tablets in sterile water, or another appropriate vehicle, solutions can be prepared in unit-dose form. Suitable excipients include, but are not limited to, inert diluents, such as calcium carbonate, sodium carbonate or bicarbonate, lactose, or calcium phosphate; or binding agents, such as starch, gelatin, or acacia; or lubricating agents such as magnesium stearate, stearic acid, or talc.

[0341] Additional pharmaceutical compositions of the disclosure will be evident to those skilled in the art, including formulations involving binding proteins in sustained- or controlled-delivery formulations. Techniques for formulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. Additional examples of sustained-release preparations include semipermeable polymer matrices in the form of shaped articles, e.g. films, or microcapsules. Sustained release matrices can include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma ethyl-L-glutamate, poly(2-hydroxyethyl-methacrylate), ethylene vinyl acetate, or poly-D(?)-3-hydroxybutyric acid. Sustained-release compositions can also include liposomes, which can be prepared by any of several methods known in the art.

[0342] Pharmaceutical compositions to be used for in vivo administration typically must be sterile. This can be accomplished by filtration through sterile filtration membranes. Where the composition is lyophilized, sterilization using this method can be conducted either prior to, or following, lyophilization and reconstitution. The composition for parenteral administration can be stored in lyophilized form or in a solution. In addition, parenteral compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

[0343] Once the pharmaceutical composition has been formulated, it can be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or as a dehydrated or lyophilized powder. Such formulations can be stored either in a ready-to-use form or in a form (e.g., lyophilized) requiring reconstitution prior to administration.

[0344] The disclosure also encompasses kits for producing a single-dose administration unit. The kits can each contain both a first container having a dried protein and a second container having an aqueous formulation. Also included within the scope of this disclosure are kits containing single and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes).

[0345] The effective amount of a binding protein pharmaceutical composition to be employed therapeutically will depend, for example, upon the therapeutic context and objectives. One skilled in the art will appreciate that the appropriate dosage levels for treatment will thus vary depending, in part, upon the molecule delivered, the indication for which the binding protein is being used, the route of administration, and the size (body weight, body surface, or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician can titer the dosage and modify the route of administration to obtain the optimal therapeutic effect.

[0346] Dosing frequency will depend upon the pharmacokinetic parameters of the binding protein in the formulation being used. Typically, a clinician will administer the composition until a dosage is reached that achieves the desired effect. The composition can therefore be administered as a single dose, as two or more doses (which may or may not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter. Further refinement of the appropriate dosage is routinely made by those of ordinary skill in the art and is within the ambit of tasks routinely performed by them. Appropriate dosages can be ascertained through use of appropriate dose-response data.

[0347] The route of administration of the pharmaceutical composition is in accord with known methods, e.g., orally; through injection by intravenous, intraperitoneal, intracerebral (intraparenchymal), intracerebroventricular, intramuscular, intraocular, intraarterial, intraportal, or intralesional routes; by sustained release systems; or by implantation devices. Where desired, the compositions can be administered by bolus injection or continuously by infusion, or by implantation device.

[0348] The composition can also be administered locally via implantation of a membrane, sponge, or other appropriate material onto which the desired molecule has been absorbed or encapsulated. Where an implantation device is used, the device can be implanted into any suitable tissue or organ, and delivery of the desired molecule can be via diffusion, timed-release bolus, or continuous administration.

[0349] The pharmaceutical compositions can be used to prevent and/or treat HIV infection. The pharmaceutical compositions can be used as a standalone therapy or in combination with standard anti-retroviral therapy.

[0350] In some embodiments, the present disclosure relates to a method of preventing and/or treating HIV infection in a patient. In some embodiments, the method comprises administering to the patient a therapeutically effective amount of at least one of the binding proteins described herein. In some embodiments, the at least one binding protein is administered in combination with an anti-retroviral therapy (e.g., an anti-HIV therapy). In some embodiments, the at least one binding protein is administered before the anti-retroviral therapy. In some embodiments, the at least one binding protein is administered concurrently with the anti-retroviral therapy. In some embodiments, the at least one binding protein is administered after the anti-retroviral therapy. In some embodiments, the at least one binding protein is co-administered with any standard anti-retroviral therapy known in the art. In some embodiments, administration of the at least one binding protein results in neutralization of one or more HIV virions. In some embodiments, administration of the at least one binding protein results in elimination of one or more latently and/or chronically HIV-infected cells in the patient. In some embodiments, administration of the at least one binding protein results in neutralization of one or more HIV virions and results in elimination of one or more latently and/or chronically HIV-infected cells in the patient. In some embodiments, the patient is a human.

[0351] Without limiting the present disclosure, a number of embodiments of the present disclosure are described below for purpose of illustration.

[0352] Item 1: A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L3-V.sub.H2-L4-C.sub.H1[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-CL[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0353] Item 2: A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is an immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0354] Item 3: The binding protein of item 1 or item 2, wherein the one or more HIV target proteins is selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 60.

[0355] Item 4: The binding protein of item 1 or item 2, wherein the binding protein is trispecific and capable of specifically binding three different epitopes on a single HIV target protein.

[0356] Item 5: The binding protein of item 1 or item 2, wherein the binding protein is trispecific and capable of specifically binding two different epitopes on a first HIV target protein, and one epitope on a second HIV target protein, wherein the first and second HIV target proteins are different.

[0357] Item 6: The binding protein of item 1 or item 2, wherein the binding protein is trispecific and capable of specifically binding three different antigen targets.

[0358] Item 7: The binding protein of item 1 or item 2, wherein the binding protein is capable of inhibiting the function of one or more HIV target proteins.

[0359] Item 8: The binding protein of any one of items 1-7, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

[0360] Item 9: The binding protein of any one of items 1-7, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0361] Item 10: The binding protein of any one of items 1-9, wherein V.sub.L1 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0362] Item 11: The binding protein of any one of items 1-10, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

[0363] Item 12: The binding protein of any one of items 1-10, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0364] Item 13: The binding protein of any one of items 1-12, wherein V.sub.L2 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0365] Item 14: The binding protein of any one of items 1-13, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively.

[0366] Item 15: The binding protein of any one of items 1-13, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0367] Item 16: The binding protein of any one of items 1-15, wherein V.sub.L3 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521.

[0368] Item 17: The binding protein of any one of items 1-16, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

[0369] Item 18: The binding protein of any one of items 1-16, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0370] Item 19: The binding protein of any one of items 1-18, wherein V.sub.H1 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0371] Item 20: The binding protein of any one of items 1-19, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively, a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

[0372] Item 21: The binding protein of any one of items 1-19, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0373] Item 22: The binding protein of any one of items 1-21, wherein V.sub.H2 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0374] Item 23: The binding protein of any one of items 1-22, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively.

[0375] Item 24: The binding protein of any one of items 1-22, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0376] Item 25: The binding protein of any one of items 1-24, wherein V.sub.H3 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508.

[0377] Item 26: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 266, a CDR-L2 comprising the sequence of SEQ ID NO: 267, and a CDR-L3 comprising the sequence of SEQ ID NO: 268; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 248, a CDR-H2 comprising the sequence of SEQ ID NO: 497, and a CDR-H3 comprising the sequence of SEQ ID NO: 250.

[0378] Item 27: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 512; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504, V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 502.

[0379] Item 28: The binding protein of any one of items 1-27, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 512; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 502.

[0380] Item 29: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

[0381] Item 30: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

[0382] Item 31: The binding protein of any one of items 1-25 and 29-30, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

[0383] Item 32: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

[0384] Item 33: The binding protein of any one of items 1-25, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

[0385] Item 34: The binding protein of any one of items 1-25 and 32-33, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

[0386] Item 35: The binding protein of item 1, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0387] Item 36: The binding protein of item 1, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0388] Item 37: The binding protein of item 1, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0389] Item 38: The binding protein of item 1, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0390] Item 39: The binding protein of any one of items 1, 37, and 38, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0391] Item 40: The binding protein of item 2, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0392] Item 41: The binding protein of item 2, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0393] Item 42: The binding protein of any one of items 2, 40, and 41, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0394] Item 43: The binding protein of item 1 or item 2, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

[0395] Item 44: The binding protein of item 1 or item 2, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

[0396] Item 45: The binding protein of any one of items 1-44, wherein L.sub.1 comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525).

[0397] Item 46: A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;
wherein:

[0398] (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or

[0399] (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and

wherein:

[0400] (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or

[0401] (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265.

[0402] Item 47: A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;
wherein:

[0403] (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or

[0404] (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and

wherein:

[0405] (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or

[0406] (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265.

[0407] Item 48: The binding protein of item 46, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0408] Item 49: The binding protein of item 46, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0409] Item 50: The binding protein of item 46, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0410] Item 51: The binding protein of item 46, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0411] Item 52: The binding protein of any one of items 46, 50, and 51, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0412] Item 53: The binding protein of item 47, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0413] Item 54: The binding protein of item 47, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0414] Item 55: The binding protein of any one of items 47, 53, and 54, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0415] Item 56: The binding protein of item 46 or item 47, wherein at least one of L.sub.1, L.sub.2, L.sub.3 or L.sub.4 is independently 0 amino acids in length.

[0416] Item 57: The binding protein of item 46 or item 47, wherein L.sub.1, L.sub.2, L.sub.3 or L.sub.4 are each independently at least one amino acid in length.

[0417] Item 58: The binding protein of any one of items 46-57, wherein L.sub.1 comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525).

[0418] Item 59: A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein:

[0419] (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2;

[0420] (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 9; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10;

[0421] (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 20; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 19; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18;

[0422] (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 28 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 28; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 27 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 27; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 25 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 25; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 26 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 26;

[0423] (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34;

[0424] (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 44; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 43 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 43; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 41; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 42;

[0425] (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 52 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 52; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 51 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 49 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 49; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 50;

[0426] (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 60 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 60; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 59 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 59; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 57 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 57; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 58;

[0427] (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66;

[0428] (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73, and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74;

[0429] (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 84; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82;

[0430] (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:92; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90;

[0431] (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98;

[0432] (n) the first polypeptide comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106;

[0433] (o) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114;

[0434] (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122;

[0435] (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130;

[0436] (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138;

[0437] (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146;

[0438] (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154;

[0439] (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162;

[0440] (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170;

[0441] (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 180 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 180; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 179 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 179; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 177 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 177; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 178 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178;

[0442] (x) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 188 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 188; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 187 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 187; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 185 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 185; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 186 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 186;

[0443] (y) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 196 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 196; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 195 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 195; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 193 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 194 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 194;

[0444] (z) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 204 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 204; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 203 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 201 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 202 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202;

[0445] (aa) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 212; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 211 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 211; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 209 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 209; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 210 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 210;

[0446] (bb) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 220 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 219 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 219; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 217 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 217; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 218 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 218;

[0447] (cc) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 228 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 228; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 227 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 227; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 225 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 225; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 226 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 226;

[0448] (dd) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 235 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 234 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 234; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 232 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 232; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 233 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; or

[0449] (ee) first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 243 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 242 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 242; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 240 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 240; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 241 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241.

[0450] Item 60: A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I];

a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II];

a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1[III];

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV];

wherein
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0451] Item 61: A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I];

a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II];

a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III];

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV];

wherein
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.

[0452] Item 62: The binding protein of item 60 or item 61, wherein the one or more HIV target proteins are selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 160.

[0453] Item 63: The binding protein of item 60 or item 61, wherein the one or more T cell target proteins are CD3 or CD28.

[0454] Item 64: The binding protein of item 60 or item 61, wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different epitopes on a single T cell target protein.

[0455] Item 65: The binding protein of item 60 or item 61, wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different T cell target proteins.

[0456] Item 66: The binding protein of item 60 or item 61, wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different epitopes on a single HIV target protein.

[0457] Item 67: The binding protein of item 60 or item 61, wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different HIV target proteins.

[0458] Item 68: The binding protein of item 60 or item 61, wherein the first and second polypeptide chains form two antigen binding sites that specifically target two T cell target proteins, and the third and fourth polypeptide chains form an antigen binding site that specifically binds an HIV target protein.

[0459] Item 69: The binding protein of any one of items 60-68, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

[0460] Item 70: The binding protein of any one of items 60-68, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0461] Item 71: The binding protein of any one of items 60-70, wherein V.sub.L1 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0462] Item 72: The binding protein of any one of items 60-71, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

[0463] Item 73: The binding protein of any one of items 60-71, wherein V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0464] Item 74: The binding protein of any one of items 60-73, wherein V.sub.L2 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0465] Item 75: The binding protein of any one of items 60-74, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively.

[0466] Item 76: The binding protein of any one of items 60-74, wherein V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0467] Item 77: The binding protein of any one of items 60-76, wherein V.sub.L3 comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524.

[0468] Item 78: The binding protein of any one of items 60-77, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

[0469] Item 79: The binding protein of any one of items 60-77, wherein V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0470] Item 80: The binding protein of any one of items 60-79, wherein V.sub.H1 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0471] Item 81: The binding protein of any one of items 60-80, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

[0472] Item 82: The binding protein of any one of items 60-80, wherein V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0473] Item 83: The binding protein of any one of items 60-82, wherein V.sub.H2 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0474] Item 84: The binding protein of any one of items 60-83, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively, a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively.

[0475] Item 85: The binding protein of any one of items 60-83, wherein V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0476] Item 86: The binding protein of any one of items 60-85, wherein V.sub.H3 comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511.

[0477] Item 87: The binding protein of any one of items 60-86, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

[0478] Item 88: The binding protein of any one of items 60-86, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

[0479] Item 89: The binding protein of any one of items 60-88, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

[0480] Item 90: The binding protein of any one of items 60-86, wherein V.sub.L1 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V.sub.L2 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V.sub.L3 comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V.sub.H1 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; V.sub.H2 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; and V.sub.H3 comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253.

[0481] Item 91: The binding protein of any one of items 60-86, wherein V.sub.L1 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V.sub.L2 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V.sub.L3 comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V.sub.H1 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; V.sub.H2 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; and V.sub.H3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503.

[0482] Item 92: The binding protein of any one of items 60-86 and 90-91, wherein V.sub.L1 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V.sub.L2 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V.sub.L3 comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V.sub.H1 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; V.sub.H2 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; and V.sub.H3 comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503.

[0483] Item 93: The binding protein of item 60, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0484] Item 94: The binding protein of item 60, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0485] Item 95: The binding protein of item 60, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0486] Item 96: The binding protein of item 60, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0487] Item 97: The binding protein of any one of items 60, 95, and 96, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0488] Item 98: The binding protein of item 61, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0489] Item 99: The binding protein of item 61, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0490] Item 100: The binding protein of any one of items 61, 98, and 99, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0491] Item 101: The binding protein of item 60 or item 61, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

[0492] Item 102: The binding protein of item 60 or item 61, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

[0493] 1 Item 103: The binding protein of any one of items 60-102, wherein L.sub.1 is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299).

[0494] Item 104: A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;
wherein:

[0495] (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or

[0496] (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and

wherein:

[0497] (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or

[0498] (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487.

[0499] Item 105: A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:

V.sub.L2-L.sub.1-V.sub.L1-L.sub.2-C.sub.L[I]

and a second polypeptide chain comprises a structure represented by the formula:

V.sub.H1-L.sub.3-V.sub.H2-L.sub.4-C.sub.H1-hinge-C.sub.H2-C.sub.H3[II]

and a third polypeptide chain comprises a structure represented by the formula:

V.sub.H3-C.sub.H1-hinge-C.sub.H2-C.sub.H3[III]

and a fourth polypeptide chain comprises a structure represented by the formula:

V.sub.L3-C.sub.L[IV]

wherein:
V.sub.L1 is a first immunoglobulin light chain variable domain;
V.sub.L2 is a second immunoglobulin light chain variable domain;
V.sub.L3 is a third immunoglobulin light chain variable domain;
V.sub.H1 is a first immunoglobulin heavy chain variable domain;
V.sub.H2 is a second immunoglobulin heavy chain variable domain;
V.sub.H3 is a third immunoglobulin heavy chain variable domain;
C.sub.L is an immunoglobulin light chain constant domain;
C.sub.H1 is the immunoglobulin C.sub.H1 heavy chain constant domain;
C.sub.H2 is an immunoglobulin C.sub.H2 heavy chain constant domain;
C.sub.H3 is an immunoglobulin C.sub.H3 heavy chain constant domain;
hinge is an immunoglobulin hinge region connecting the C.sub.H1 and C.sub.H2 domains; and
L.sub.1, L.sub.2, L.sub.3, and L.sub.4 are amino acid linkers;
wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;
wherein:

[0500] (a) V.sub.L1, V.sub.L2 and V.sub.L3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or

[0501] (b) V.sub.L1, V.sub.L2 and V.sub.L3 each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and

wherein:

[0502] (a) V.sub.H1, V.sub.H2, and V.sub.H3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or

[0503] (b) V.sub.H1, V.sub.H2, and V.sub.H3 each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487.

[0504] Item 106: The binding protein of item 104, wherein the second polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0505] Item 107: The binding protein of item 104, wherein the third polypeptide chain further comprises an Fc region linked to C.sub.H1, the Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains.

[0506] Item 108: The binding protein of item 104, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.Ht, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0507] Item 109: The binding protein of item 104, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0508] Item 110: The binding protein of any one of items 104, 108, and 109, wherein the second polypeptide chain further comprises a first Fc region linked to C.sub.H1, the first Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C.sub.H1, the second Fc region comprising an immunoglobulin hinge region and C.sub.H2 and C.sub.H3 immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0509] Item 111: The binding protein of item 105, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

[0510] Item 112: The binding protein of item 105, wherein the C.sub.H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C.sub.H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.

[0511] Item 113: The binding protein of any one of items 105, 111, and 112, wherein the C.sub.H3 domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.

[0512] Item 114: The binding protein of item 104 or item 105, wherein at least one of L.sub.1, L.sub.2, L.sub.3, or L.sub.4 is independently 0 amino acids in length.

[0513] Item 115: The binding protein of item 104 or item 105, wherein L.sub.1, L.sub.2, L.sub.3, or L.sub.4 are each independently at least one amino acid in length.

[0514] Item 116: The binding protein of any one of items 104-115, wherein L.sub.1 is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299).

[0515] Item 117: A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein:

[0516] (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 305 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 305; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 304 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 302 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 302; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 303 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303;

[0517] (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 313 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 313; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 312 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 312; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 310 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 310; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 311 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 311;

[0518] (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 321 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 321; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 320 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 320; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 318 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 318; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 319 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319;

[0519] (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 329 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 329; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 328 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 328; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 326 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 326; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 327 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 327;

[0520] (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 337 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 336 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 336; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 334 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 334; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 335 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 335;

[0521] (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 345 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 345; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 344 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 344; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 342 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 342; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 343 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 343;

[0522] (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 353 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 353; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:352; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 350 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 350; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 351 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 351;

[0523] (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 361 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 361; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 360 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 360; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 358 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 358; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 359 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 359;

[0524] (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 369 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 369; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 368 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 368; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 366 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 366; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 367 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 367;

[0525] (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 377 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 377; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 376 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 376; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 374 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 374; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 375 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 375;

[0526] (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 385 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 385; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 384 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 384; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 382 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 382; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 383 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 383;

[0527] (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 393 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 393; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 392 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 392; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 390 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 390; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 391 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 391;

[0528] (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 401 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 401; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 400 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 400; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 398 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 398; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 399 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 399;

[0529] (n) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 409 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 409; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 408 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 408; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 406 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 407 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 407;

[0530] (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 417 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 417; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 416 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 416; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 414 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 414; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 415 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 415;

[0531] (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 425 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 425; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 424 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 424; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 422 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 422; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 423 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 423;

[0532] (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 433 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:433; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 432 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 432; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 430 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 430; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 431 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 431;

[0533] (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 441 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 441; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 440 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 438 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 438; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 439 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439;

[0534] (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 449 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 449; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 448 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 448; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 446 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 446; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 447 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 447;

[0535] (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 457 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 457; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 456 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 456; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 454 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 454; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 455 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 455;

[0536] (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 465 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 465; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 464 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 464; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 462 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 462; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 463 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 463; or

[0537] (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 473 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 473; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 472 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 472; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 470 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 470; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 471 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 471.

[0538] Item 118: An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding protein of any one of items 1-117.

[0539] Item 119: An expression vector comprising the nucleic acid molecule of item 118.

[0540] Item 120: An isolated host cell comprising the nucleic acid molecule of item 118.

[0541] Item 121: An isolated host cell comprising the expression vector of item 119.

[0542] Item 122: The isolated host cell of item 120 or item 121, wherein the host cell is a mammalian cell or an insect cell.

[0543] Item 123: A vector system comprising one or more vectors encoding a first, second, third, and fourth polypeptide chain of a binding protein of any one of items 1-117.

[0544] Item 124: The vector system of item 123, wherein the vector system comprises a first vector encoding the first polypeptide chain of the binding protein, a second vector encoding the second polypeptide chain of the binding protein, a third vector encoding the third polypeptide chain of the binding protein, and a fourth vector encoding the fourth polypeptide chain of the binding protein.

[0545] Item 125: The vector system of item 123, wherein the vector system comprises a first vector encoding the first and second polypeptide chains of the binding protein, and a second vector encoding the third and fourth polypeptide chains of the binding protein.

[0546] Item 126: The vector system of any one of items 123-125, wherein the one or more vectors are expression vectors.

[0547] Item 127: An isolated host cell comprising the vector system of any one of items 123-126.

[0548] Item 128: The isolated host cell of item 127, wherein the host cell is a mammalian cell or an insect cell.

[0549] Item 129: A method of producing a binding protein, the method comprising:

a) culturing a host cell of any one of items 120-122 and items 127-128 under conditions such that the host cell expresses the binding protein; and
b) isolating the binding protein from the host cell.

[0550] Item 130: A method of preventing and/or treating HIV infection in a patient comprising administering to the patient a therapeutically effective amount of at least one binding protein of any one of items 1-117.

[0551] Item 131: The method of item 130, wherein the binding protein is co-administered with standard anti-retroviral therapy.

[0552] Item 132: The method of item 130 or item 131, wherein administration of the at least one binding protein results in the neutralization of one or more HIV virions.

[0553] Item 133: The method of any one of items 130-132, wherein administration of the at least one binding protein results in the elimination of one or more latently and/or chronically HIV-infected cells in the patient.

[0554] Item 134: The method of any one of items 130-133, wherein the patient is a human.

[0555] Item 135: The binding protein of any one of items 1-117 for the prevention or treatment of an HIV infection in a patient.

[0556] Item 136: The binding protein of item 135, wherein the binding protein is co-administered with standard anti-retroviral therapy.

[0557] Item 137: The binding protein of item 135 or item 136, wherein the binding protein causes the neutralization of one or more HIV virions in the patient.

[0558] Item 138: The binding protein of any one of items 135-137, wherein the binding protein causes the elimination of one or more latently and/or chronically HIV-infected cells in the patient.

[0559] Item 139: The binding protein of any one of items 135-138, wherein the patient is a human.

EXAMPLES

[0560] The Examples that follow are illustrative of specific embodiments of the disclosure, and various uses thereof. They are set forth for explanatory purposes only, and should not be construed as limiting the scope of the invention in any way.

Example 1: Production of Trispecific Binding Proteins Targeting the HIV-1 Env Glycoprotein

[0561] The HIV-1 envelope glycoprotein (Env/gp160) is located on the surface of the virus particle, and is composed of a homo-trimer comprising three non-covalently-linked transmembrane gp41 and gp120 complexes. Env enables viral entry into target cells by the binding of gp120 to HIV's main receptor (CD4) and co-receptor (CCR5 or CXCR4), followed by the induction of viral/cellular membrane fusion facilitated by conformational changes in gp41, resulting in entry of the viral capsid and delivery of the viral genome into the host cell. Additionally, Env is expressed on the surface of infected cells.

[0562] Env acts as the only target for neutralizing antibodies on the HIV-1 virion. Binding of neutralizing antibodies to viral Env inhibits viral attachment/entry. Moreover, binding of neutralizing antibodies to HIV-1 infected, Env expressing cells leads to their destruction by Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC), resulting in reduction of the latent viral reservoir. Thus, neutralizing antibodies targeting Env are an attractive area for anti-viral therapy development. However, because of the high sequence diversity and mutation rate of the HIV-1 virus, developing neutralizing antibodies targeting Env has proven challenging due to the high likelihood that a given HIV-1 strain either lacks the epitope of any given neutralizing antibody, or the strain has evolved a mutation to become resistant to the antibody. Strategies must be developed to mitigate the breakthrough of viral strains when developing novel neutralizing antibodies targeting HIV-1. The studies described herein explore the development of novel trispecific binding proteins comprising four polypeptides forming three antigen binding sites that specifically bind three different epitopes on the HIV Env glycoprotein, and use of these novel trispecific binding proteins in neutralizing HIV-1.

[0563] Methods

Binding Protein Production and Purification

[0564] The vectors expressing the trispecific binding proteins were constructed by inserting the designed heavy and light chain genes into a mammalian expression vector. Corresponding heavy and light chain pairing occurred spontaneously, and heterodimer formation was promoted by Knob-in-Hole mutations engineered in the Fc region.

[0565] Binding proteins were produced in Expi293 cells by cotransfection of four expression plasmids (Life Technologies, Expi293? Expression System Kit, Cat. No. A14635). Binding proteins were purified using a two-step purification scheme. First, binding proteins were captured on protein A affinity chromatography resin, washed, and then eluted in glycine at pH 3.0. The eluted proteins were then dialyzed in PBS, concentrated, and filtered. The filtered antibodies were further purified using a Superdex 200 SEC column to obtain monomeric binding proteins.

Affinity Measurements of the Binding Proteins

[0566] Binding affinities of anti-HIV trispecific binding proteins were measured by surface plasmon resonance (SPR) using a Biacore3000 instrument (GE Healthcare). The assay buffer used was HBS-EP (GE Healthcare).

[0567] The affinity of the indicated proteins for the MPER binding site on the HIV-1 protein gp41 was measured by surface plasmon resonance (SPR) analysis using a Biacore Instrument as follows: binding proteins were first captured on a CM5 chip coupled with anti-human Fc antibody, followed by flow through of varying concentrations (100 nM-6.25 nM) of the MPER binding peptide (Acetyl-RRRNEQELLELDKWASLWNWFDITNWLWYIRRR-Ttds-Lys-(Biotin)-NH.sub.2) (SEQ ID NO: 284) at 30 ?L per minute, and binding was detected by measurement of association for 240 seconds, and dissociation for 300 seconds on a Biacore 3000 at 25? C. HBS-EP buffer was used for sample dilution, as well as running buffer. Regeneration of the chip was done with 3 M MgCl.sub.2 at 30 ?L per minute. For data analysis the BIAevaluation software v.4.1 (GE Healthcare) was used. Data were fit globally using a 1:1 Langmuir model with mass transfer. After software-based curve fitting, the ON and OFF reates at each concentration of MPER binding peptide was calculated and used to obtain a binding affinity for each binding protein.

[0568] The affinity of the indicated proteins for the CD4BS binding site on the HIV-1 protein gp120 was measured by SPR as follows: recombinant HIV-1 gp120 (Thr27-Arg498) protein (HIV-1/Clade B/C (CN54), ARCO Biosystems (Cat. # GP4-V15227)) was captured on a CM5 chip, followed by flow through of varying concentrations (100 nM-6.25 nM) of the binding proteins, and binding was detected by measurement of association for 240 seconds, and dissociation for 300 seconds on a Biacore 3000 at 25? C. HBS-EP buffer was used for sample dilution, as well as running buffer. Regeneration of the chip was done with 3 M MgCl.sub.2 at 30 ?L per minute. For data analysis the BIAevaluation software v.4.1 (GE Healthcare) was used. Data were fit globally using a 1:1 Langmuir model with mass transfer. After software-based curve fitting, the ON and OFF reates at each concentration of Binding Protein was calculated and used to obtain a binding affinity for each binding protein.

Conformational Stability and Aggregation Assays

[0569] Conformational stability of the trispecific binding proteins was assessed by determining the melting point T.sub.m and aggregation onset temperature (T.sub.agg).

[0570] Melting point T.sub.m measurements were performed by differential scanning fluorimetry (DSF). Samples were diluted in D-PBS buffer (Invitrogen) to a final concentration of 0.2 ?g/?L including a 4? concentration solution of SYPRO-Orange dye (Invitrogen, 5000? stock in DMSO) in D-PBS in white sem-skirt 96-well plates (BIORAD). All measurements were done in duplicate using a MyiQ2 real time PCR instrument (BIORAD). Negative first derivative curves (?d(RFU)/dT) of the melting curves were generated in the iQ5 software v2.1 (BIORAD). Data were then exported into Excel for T.sub.m determination and graphical display.

[0571] Melting Point T.sub.m and aggregation onset temperature (T.sub.agg) were also measured by static light scattering (SLS) using a Unit instrument (Unchained Labs). 9 ?L of each sample was loaded undiluted into a multicuvette array. The samples were then heated from 20? C. to 95? C. at a heating rate of 0.3? C./minute. The barycentric mean (BCM) of the tryptophan fluorescence spectra was used to measure the protein melting curve, and determine the T.sub.m values. The 266 nm static light scattering (SLS) signal was used to measure the aggregation curve and determine the T.sub.agg. Data analysis was performed using the Unit analysis software v2.1.

[0572] Results

[0573] A novel strategy was developed for improving neutralizing antibody efficacy against HIV-1, while concomitantly limiting the likelihood of viral breakthrough due to high sequence diversity and/or viral mutation. This strategy involved the generation of trispecific binding proteins comprising four polypeptides that formed three antigen binding sites that specifically bind three different epitopes on the HIV Env glycoprotein (FIG. 1). Each antigen binding site comprised the V.sub.H and V.sub.L domain from a different HIV-1 neutralizing antibody that targeted a distinct epitope on the Env glycoprotein. The trispecific binding proteins contained a first pair of polypeptides that possessed dual variable domains having a cross-over orientation forming two distinct antigen binding sites (called the CODV Ig format), and a second pair of polypeptides, each with a single variable domain that formed a third antigen binding site (FIGS. 1A and 1B).

[0574] The first pair of polypeptides (that possessed the dual variable domains) comprised a first polypeptide having the structure V.sub.L2-Linker-V.sub.L1-Linker-Immunoglobulin light chain constant domain, and a second polypeptide having the structure V.sub.H1-Linker-V.sub.H2-Linker-Immunoglobulin C.sub.H1, hinge, C.sub.H2, and C.sub.H3 heavy chain constant domains, resulting in a pair of polypeptides which had a cross over orientation that formed two distinct antigen binding sites: V.sub.H1-V.sub.L1 and V.sub.H2-V.sub.L2 (FIGS. 1C and 1D, see light and heavy chains B). The second pair of polypeptides (that each possessed a single variable domain) comprised a first polypeptide having the structure V.sub.H3-Immunoglobulin C.sub.H1, hinge, C.sub.H2, and C.sub.H3 heavy chain constant domains, and a second polypeptide having the structure V.sub.L3-Immunoglobulin light chain constant domain, resulting in a pair of polypeptides that formed a third antigen binding site: V.sub.H3-V.sub.L3 (FIGS. 1C and 1D, see light and heavy chains A). In addition, the trispecific binding proteins were constructed to include an LS mutation. Furthermore, the trispecific binding proteins were constructed such that within one binding protein, one C.sub.H3 domain included a knob mutation and the other C.sub.H3 domain included a hole mutation to facilitate heterodimerization of the heavy chains (FIG. 1).

[0575] Using the above described approach for trivalent binding protein design, three trispecific binding proteins (Binding Proteins 2, 3, and 24) were generated. These trispecific binding proteins were created by grafting onto a trispecific binding protein framework the V.sub.H and V.sub.L domains isolated from antibodies targeting three distinct epitopes on the HIV-1 Env glycoprotein: MPER Ab (targeting the MPER epitope on gp41), CD4BS Ab b (targeting the CD4 Binding Site on gp120), and V1/V2 directed Ab a (targeting the V1/V2 domain on gp120). Binding Protein 2 was constructed such that the first pair of polypeptides (which formed two antigen binding sites) targeted the HIV-1 Env glycoprotein epitopes MPER and V1/V2, and the second pair of polypeptides (which formed the single antigen binding site) targeted the HIV-1 Env glycoprotein epitope CD4BS (Binding Protein 2=MPER?V1/V2/CD4BS). Binding Protein 3 was constructed such that the first pair of polypeptides (which formed two antigen binding sites) targeted the HIV-1 Env glycoprotein epitopes V1/V2 and MPER, and the second pair of polypeptides (which formed the single antigen binding site) targeted the HIV-1 Env glycoprotein epitope CD4BS (Binding Protein 3=V1/V2?MPER/CD4BS). Binding Protein 24 was constructed such that the first pair of polypeptides (which formed two antigen binding sites) targeted the HIV-1 Env glycoprotein epitopes V1/V2 and CD4BS, and the second pair of polypeptides (which formed the single antigen binding site) targeted the HIV-1 Env glycoprotein epitope MPER (Binding Protein 24=V1/V2?CD4BS/MPER). The three trispecific binding proteins, as well as their parental antibodies, were purified over protein A affinity resin (FIGS. 2A and 3A) followed by size exclusion chromatography (FIGS. 2B and 3B) to obtain monomeric proteins suitable for further characterization. All three trispecific binding proteins were stable and formed monomers at high frequency.

[0576] To test the potential for developing binding proteins targeting two different HIV-1 Env protein epitopes (instead of three), bispecific binding proteins were designed based upon the above described CODV Ig format (See WO 2012/135345), using two different V.sub.H and V.sub.L domains from the same parental antibodies used to create the trispecific binding proteins. However, the bispecific binding proteins with these specific variable domains did not purify well as monomers, showing significantly increased aggregate formation when compared to the corresponding trispecific binding proteins (FIGS. 4A and 4B).

[0577] Next, the binding affinity of the purified trispecific binding proteins (and their parental antibodies) was measured for the HIV-1 Env glycoprotein epitopes on gp41 and gp120. First, the binding affinity for gp41 was measured for the three trispecific binding proteins, as well as the parental MPER antibody, by Biacore assay using the MPER binding peptide (FIG. 5). The binding affinity for the MPER antibody was calculated to be 18.7 nM. Surprisingly, the three trispecific binding proteins all had a higher affinity for the MPER binding peptide than did the parental antibody (Table 3), with Binding Protein 2 having an approximately 3.1 fold higher affinity than the MPER antibody (6.05 nM vs. 18.7 nM, respectively).

TABLE-US-00001 TABLE 3 Affinity measurements for the MPER binding peptide MW ka kd Rmax KA KD MPER Antibody Analyte (1/Ms) (1/s) (RU) (1/M) (M) Chi2 (kDa) MPER Ab Gp41- 5.85E+04 1.09E?03 47.5 5.35E+07 1.87E?08 0.55 5.25 MPER JPT Binding Gp41- 1.15E+05 6.97E?04 29.0 1.65E+08 6.05E?09 0.27 2.29 Protein 2 MPER JPT Binding Gp41- 4.67E+04 7.79E?04 38.5 6.00E+07 1.67E?08 0.41 5.14 Protein 3 MPER JPT Binding Gp41- 6.28E+04 8.06E?04 35.5 7.80E+07 1.28E?08 0.48 5.24 Protein 24 MPER JPT

[0578] Similarly, the binding affinity for the CD4 Binding Site on gp120 was measured for the three trispecific binding proteins, as well as the parental CD4BS antibody, by Biacore assay (FIG. 6). The three trispecific binding proteins all had a similar affinity for the CD4 Binding Site when compared to the parental antibody (Table 4).

TABLE-US-00002 TABLE 4 Affinity measurements for the CD4BS binding site Antibody ka (1/Ms) kd (1/s) Rmax (RU) KD (M) Chi2 CD4BS 2.79E+05 2.32E?04 31.4 8.30E?10 1.17 Ab b Binding 2.31E+05 2.41E?04 34.0 1.04E?09 0.74 Protein 2 Binding 7.58E+04 2.75E?04 38.2 3.63E?09 0.19 Protein 3 Binding 1.46E+05 2.52E?04 41.6 1.73E?09 0.38 Protein 24

[0579] Thus, the trispecific binding proteins were able to bind both of the tested target epitopes on the HIV-1 Env glycoprotein (Table 5). Moreover, all three trispecific binding proteins bound the target epitopes with affinities approximately equal to or exceeding those of their parental antibodies. Binding affinity of the V1/V2 directed Ab a, as well as of the V1/V2 directed Ab a binding sites within the three trispecific binding proteins 2, 3, and 24 could not be determined by Biacore analysis because this required a specific gp120 protein antigen which was unavailable.

TABLE-US-00003 TABLE 5 Summary of binding capabilities of tested binding proteins Binding on Binding on Sample gp120? gp41? MPER Ab No Yes CD4BS Ab b Yes No V1/V2 directed No No Ab a Binding Yes Yes Protein 2 Binding Yes Yes Protein 3 Binding Yes Yes Protein 24

[0580] The biophysical properties were tested for the trispecific binding proteins and parental antibodies (Table 6). All of the tested proteins had similar stabilities and limited propensities to form aggregates.

TABLE-US-00004 TABLE 6 Conformational stability/aggregation of the binding proteins SLS at Intrinsic AA 266 nm DSF T.sub.m Fluo T.sub.m T.sub.agg Sample (? C.) (? C.) (? C.) MPER Ab 69/75 68 71 CD4BS Ab b 69 66 68 V1/V2 directed 69 64 67 Ab a Binding 60/70 54 58 Protein 2 Binding 57/70 55 56 Protein 3 Binding 56/71 53 54 Protein 24

[0581] These experiments indicated that stable, monomeric, trispecific binding proteins targeting three distinct epitopes on the HIV-1 Env glycoprotein could be constructed and efficiently purified. Furthermore, the trispecific binding proteins retained their ability to bind their target epitopes, having similar or improved affinity relative to their parental antibodies. Finally, the trispecific binding proteins had suitable biophysical properties, and showed significantly less aggregation than the corresponding bispecific binding proteins.

Example 2: Characterization of the Binding Proteins

[0582] Due to the success of developing three trispecific binding proteins with appropriate biophysical properties and binding abilities (as described in Example 1), 21 additional trispecific binding proteins were developed and tested. The experiments described herein explored the ability of the 24 trispecific binding proteins to neutralize HIV-1 in vitro, and the pharmacokinetic properties of a number of these trispecific binding proteins in vivo.

[0583] Neutralization assays were performed using the TZM-b1 assay which measures neutralization as a function of reductions in HIV-1 Tat-regulated firefly luciferase (Luc) reporter gene expression after a single round of infection with Env-pseudotyped viruses. The assays were performed as described in Marcella Sarzotti-Kelsoe et al., J. Immunological Methods, 409:131-146 (2014). The neutralization results of various antibodies are shown in Tables 8-10.

[0584] Methods

Production of Env-Pseudotyped Viruses

[0585] Assay stocks of Env-pseudotyped viruses were produced in 293T/17 cells by co-transfection with two plasmids: an Env expression plasmid and a plasmid expressing the entire HIV-1 genome except for Env. Co-transfection of these plasmids produced infectious pseudovirus particles which were capable of delivering the Tat gene into target cells, but infections with these pseudovirions could not themselves produce infectious viral progeny.

Viral Neutralization Assay

[0586] Neutralization of HIV infection using TZM-b1 cells (also known as JC53BL-13 cells) was performed as described previously (Marcella Sarzotti-Kelsoe et al., J. Immunological Methods, 409:131-146 (2014)). Briefly, a single round of infection using the Env-pseudotyped HIV-1 virions was carried out in TZM-b1 cells (a CXCR-4-positive HeLa cell clone). TZM-b1 cells were engineered to express CD4 and CCR5, and to contain integrated reporter genes for firefly luciferase and E. coli ?-galactosidase under the control of an HIV long-terminal repeat. Reporter gene expression was induced in trans by viral Tat protein (delivered by the pseudotyped viruses) soon after single cycle infection. Luciferase activity was quantified as relative luminescence units (RLU), and was directly proportional to the number of infectious virus particles present in the initial inoculum over a wide range of values. Neutralization was measured as a function of decreased Tat-regulated Firefly luciferase (Luc) reporter gene expression after administration of varying concentrations of the indicated binding proteins. Neutralization titers were identified as the protein dilution at which RLUs were reduced by 80% compared to virus control wells after subtraction of background RLUs. The assay was performed in 96-well plates for high throughput capacity, and well-characterized reference strains were utilized for uniformity across studies.

Pharmacokinetic (PK) Measurements

[0587] Female Indian rhesus macaques weighing between 3 and 6 kg were randomly assigned to groups according to body weight (two macaques per group) and were intravenously injected with the indicated concentration of binding proteins. Blood was collected from the animals before the injection on day 0, and 30 minutes, 6 hours, 1 day, 2 days, 4 days, 7 days, 14 days, 21 days and 28 days after injection. The serum concentration of each binding protein was quantified in the plasma from the collected blood using an RSC3-based ELISA assay.

[0588] Results

[0589] 21 additional trispecific binding proteins targeting three distinct HIV-1 Env glycoprotein epitopes were generated and purified as described in Example 1. These 21 additional trispecific binding proteins (Binding Proteins 1 and 4-23) were created by grafting onto a trispecific binding protein framework the V.sub.H and V.sub.L domains isolated from antibodies targeting distinct HIV-1 epitopes on the HIV-1 Env glycoprotein: the anti-MPER antibodies MPER Ab a and MPER Ab b (targeting the MPER epitope on gp41), the anti-CD4BS antibodies CD4BS Ab a and CD4BS Ab b (targeting the CD4 Binding Site on gp120), the anti-V1/V2 antibodies V1/V2 directed Ab a and V1/V2 directed Ab b (targeting the V1/V2 domain on gp120), and the anti-V3 antibody V3 directed Ab (targeting the V3 loop on gp120) (Table 7).

TABLE-US-00005 TABLE 7 Epitope binding site composition of the trispecific binding proteins Binding Protein: Epitope Binding Site: 1 MPER ? V1/V2 directed/CD4BS 2 MPER ? V1/V2 directed/CD4BS 3 V1/V2 directed ? MPER/CD4BS 4 MPER ? V1/V2 directed/CD4BS 5 MPER ? V3 directed/CD4BS 6 V1/V2 directed ? MPER/CD4BS 7 V3 directed ? V1/V2 directed/CD4BS 8 MPER ? V1/V2 directed/CD4BS 9 MPER ? V1/V2 directed/CD4BS 10 V1/V2 directed ? MPER/CD4BS 11 MPER ? V1/V2 directed/CD4BS 12 MPER ? V3 directed/CD4BS 13 MPER ? V3 directed/V1/V2 directed 14 V1/V2 directed ? MPER/CD4BS 15 MPER ? V3 directed/V1/V2 directed 16 MPER ? V3 directed/CD4BS 17 V1/V2 directed ? V3 directed/CD4BS 18 V3 directed ? MPER/CD4BS 19 V3 directed ? V1/V2 directed/MPER 20 V3 directed ? V1/V2 directed/CD4BS 21 MPER ? CD4BS/V1/V2 directed 22 CD4BS ? MPER/V1/V2 directed 23 CD4BS ? V1/V2 directed/MPER 24 V1/V2 directed ? CD4BS/MPER

[0590] The viral neutralization capabilities of five of the trispecific binding proteins (and their parental antibodies) at varying concentrations were tested against a panel of 208 different HIV-1 Env-pseudotyped viruses (Table 8). Binding protein-mediated neutralization of the pseudotyped HIV-1 isolates was measured using the TZM-b1 luciferase reporter gene assay. The inhibitory dose for each binding protein was calculated for each pseudotyped virus as the dilution that caused an 80% reduction in luminescence (IC.sub.80) after infection. Surprisingly, the IC.sub.80 geometric means calculated for each of the tested trispecific binding proteins was lower than the parental antibodies, suggesting that these trispecific binding proteins were more potent at neutralizing pseudotyped HIV-1 than their parental neutralizing antibodies.

TABLE-US-00006 TABLE 8 IC.sub.80 measurements from viral neutralization assay Parental Antibody: V1/V2 V3 Binding Protein: MPER directed directed CD4BS CD4BS 15 1 2 19 20 3 Ab Ab a Ab Ab b Ab a # Viruses 208 208 208 208 208 208 208 208 208 208 208 Total VS Neutralized: IC.sub.80 <50 ?g/mL 190 202 206 198 206 206 203 151 113 202 183 IC.sub.80 <10 ?g/mL 180 199 206 180 206 206 193 149 109 200 175 IC.sub.80 <1.0 ?g/mL 166 169 191 145 188 186 61 133 98 184 108 IC.sub.80 <0.1 ?g/mL 122 109 136 80 144 123 10 99 72 79 10 IC.sub.80 <0.01 ?g/mL 74 7 70 22 54 47 5 24 26 6 0 % VS Neutralized: IC.sub.80 <50 ?g/mL 91 97 99 95 99 99 98 73 54 97 88 IC.sub.80 <10 ?g/mL 87 96 99 87 99 99 93 72 52 96 84 IC.sub.80 <1.0 ?g/mL 80 81 92 70 90 89 29 64 47 88 52 IC.sub.80 <0.1 ?g/mL 59 52 65 38 69 59 5 48 35 38 5 IC.sub.80 <0.01 ?g/mL 36 3 34 11 26 23 2 12 13 3 0 Median IC.sub.80 0.033 0.088 0.026 0.164 0.029 0.045 1.69 0.037 0.054 0.149 0.780 Geometric Mean 0.033 0.135 0.028 0.199 0.034 0.051 1.34 0.063 0.057 0.144 0.814

[0591] Next, the viral neutralization capabilities of a larger panel of trispecific binding proteins (and their parental antibodies) at varying concentrations were tested against 20 pseudotyped viruses representing 10 different HIV-1 clades (Table 9). The trispecific binding proteins provided robust protection against infection with these 20 viruses (Table 10).

TABLE-US-00007 TABLE 9 20 representative viruses used for viral neutralization assay Virus Clade KER2008.12.SG3 A 620345.c1.SG3 AE DJ263.8.SG3 AG T266-60.SG3 AG T278-50.SG3 AG BL01.DG.SG3 B BR07.DG.SG3 B CNE57.SG3 B H086.8.SG3 B QH0692.42.SG3 B SS1196.01.SG3 B CNE21.SG3 BC 6471.V1.C16.SG3 C CAP210.E8.SG3 C DU156.12.SG3 C DU422.01.SG3 C TV1.29.SG3 C ZM106.9.SG3 C 3817.v2.c59.SG3 CD X2088.c9.SG3 G

TABLE-US-00008 TABLE 10 IC.sub.80 measurements from viral neutralization assay of 20 representative viruses Total VS Neutralized % VS Neutralized IC.sub.80 IC.sub.80 IC.sub.80 IC.sub.80 Median Geometric # Viruses <50 ?g/mL <1 ?g/mL <50 ?g/mL <1 ?g/mL IC.sub.80 Mean Binding Protein 4 20 17 11 85 55 0.474 0.398 Binding Protein 5 20 14 11 70 55 0.199 0.324 Binding Protein 6 20 16 9 80 45 0.453 0.449 Binding Protein 7 20 16 9 80 45 0.523 0.312 Binding Protein 8 20 17 12 85 60 0.578 0.488 Binding Protein 9 20 14 9 70 45 0.836 0.531 Binding Protein 10 20 16 12 80 60 0.222 0.173 Binding Protein 11 20 18 15 90 75 0.310 0.181 Binding Protein 12 20 17 12 85 60 0.526 0.566 Binding Protein 13 20 19 12 95 60 0.202 0.189 Binding Protein 14 20 17 15 85 75 0.208 0.088 Binding Protein 15 20 17 10 85 50 0.345 0.378 Binding Protein 16 20 18 11 90 55 0.228 0.314 Binding Protein 17 20 17 12 85 60 0.086 0.180 Binding Protein 18 20 15 10 75 50 0.536 0.501 Binding Protein 19 20 18 11 90 55 0.563 0.538 Binding Protein 20 20 18 14 90 70 0.224 0.229 Binding Protein 21 20 15 9 75 45 0.627 0.501 Binding Protein 2 20 18 13 90 65 0.375 0.222 Binding Protein 22 20 13 8 65 40 0.856 0.634 Binding Protein 23 20 17 6 85 30 1.930 1.129 Binding Protein 3 20 18 12 90 60 0.469 0.287 Binding Protein 24 20 16 7 80 35 2.130 1.054 MPER Ab a 20 16 8 80 40 1.007 0.981 MPER Ab b 20 16 16 80 80 0.071 0.024 CD4BS A b 20 15 9 75 45 0.181 0.399 V1/V2 directed Ab a 20 11 9 55 45 0.060 0.094 V3 directed Ab 20 12 10 60 50 0.183 0.136 CD4BS Ab a 20 10 1 50 5 1.530 1.811 V1/V2 directed Ab b 20 9 9 45 45 0.051 0.039

[0592] Finally, the pharmacokinetics (PK) of a subset of the trispecific binding proteins and parental antibodies were tested in rhesus macaques. Briefly, 10 or 20 mg/kg of the proteins were intravenously injected into female rhesus macaques, and ELISA assays were performed on the plasma from blood samples taken prior to injection, and on the plasma from blood samples taken at many time points after the injection (up to 42 days) (FIG. 7). All of the trispecific binding proteins could be detected at least 14 days after IV administration, with Binding Protein 1 remaining detectable at least 35 days after injection, showing that the binding proteins were stable in vivo.

[0593] Taken together, this data suggested that broadly neutralizing trispecific binding proteins could be constructed which targeted three distinct epitopes on the HIV-1 Env glycoprotein. These binding proteins showed similar or increased potency/much improved neutralizing capabilities (breadth) relative to the parental neutralizing antibodies. Furthermore, these trispecific binding proteins appeared to be well tolerated in vivo. Without wishing to be bound by theory, the development of broadly neutralizing trispecific binding proteins targeting multiple epitopes on HIV may allow for improved anti-viral therapy relative to monospecific or bispecific antibodies, as HIV viral particles are less likely to be resistant to all three antigen binding sites on the neutralizing trispecific binding proteins than the single or dual antigen binding sites on monospecific or bispecific neutralizing antibodies, respectively.

Example 3: Characterization of T-Cell Engagers

[0594] As noted above, Env is expressed on the surface of HIV-infected cells. Because of this, Env can act as an antibody target to identify infected cells, and induce Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC), resulting in reduction of the latent viral reservoir. The studies described herein explore the development of novel trispecific binding proteins (termed T cell engagers) that contain three antigen binding sites targeting three different antigens (HIV-1 Env glycoprotein, CD3, and CD28). These novel proteins not only include antigen binding sites from neutralizing antibodies, but also the ability to bind effector T cells, bringing them into close proximity to infected target cells, thus inducing HIV-infected cell lysis.

[0595] Methods

Binding Properties of T-Cell Engagers

[0596] The binding properties of the T-cell engagers was measured by ELISA assay using a horse radish peroxidase-conjugated anti-Fab probe to detect T-cell engager binding to the surface of ELISA plates coated with CD3, CD28, or Resurfaced Stabilized Core 3 (RSC3) protein of gp120. Human CD3ge-hIgG4 (KIH) (Cat. No: 03-01-0051) from Cambridge Biologics, MA, USA; Human CD28-hIgG4 (Cat. No: 03-01-0303) from Cambridge Biologics, MA, USA.

T-Cell Activation Assay

[0597] CD4 and CD8 T cell activation were measured as follows: peripheral blood mononuclear cells (PBMCs) were enriched from buffy coats obtained from na?ve donors (NIH blood bank) using magnetic beads (Miltenyi Biotec). These cells were co-cultured for 14-16 hours with either uninfected or HIV-1 infected CEM cells in the presence of increasing concentrations of the binding proteins (0.01-1.0 ?g/mL) with brefeldin A. The cells were then stained for surface expression of T-cell markers (CD3, CD4, and CD8) and activation markers (CD25 and CD69), followed by intracellular staining for cytokines (IFN-?, TNF-?, and IL-2) using fluorescently conjugated antibodies (BD Biosciences, eBiosciences, Biolegend). The number of CD4 and CD8 T cells expressing each cytokine or activation marker was determined by running the samples on an LSRII flow cytometer and analyzing the data with Flowjo software (Treeestar).

CD3 Downregulation

[0598] CD3 downregulation after T cell activation by the T-cell engagers was measured by staining activated PBMCs with non-competing mouse anti-human CD3 antibody and quantitated using flow cytometry.

Cytotoxicity Assay

[0599] Cytotoxicity of the T-cell engagers to CEM-BaL, ACH2, and J1.1 cells was monitored by flow cytometry as follows: latent cell lines (ACH2, J1.1, OM10) were obtained from the NIH AIDS Reagent Program. The activation of these cells was performed by culturing the cells in the presence or absence of TNF-? (10 ng/mL) for 14-16 hours. Activation was measured by determining the expression of cell surface HIV envelope glycoprotein by flow cytometry using an allophycocyanin-conjugated anti-HIV Env antibody (2G12). The CEM-IIIb, ACH2, J1.1 and OM10 cells were labeled with the membrane dye PKH-26 (Sigma) and used as target cells in a cytotoxicity assay. These labeled target cells were co-cultured for 14-16 hours at an E:T ratio of 10:1 with enriched human T cells as effector cells in the presence of increasing amounts of the binding proteins. The extent of cell lysis in the target cells was determined by staining with a live/dead cell marker (Life technologies) and measuring the number of dead cells in the labeled target cell population by running the samples on an LSRII flow cytometer followed by analysis using Flowjo software (Treestar).

[0600] Results

[0601] The capacity to develop T cell engagers with antigen binding sites targeting both T cell surface proteins and neutralizing epitopes on HIV-1 was explored. T cell engagers were constructed which contained two antigen binding sites targeting two different T cell surface receptors (CD3 and CD28), and a third antigen binding site targeting the HIV-1 Env glycoprotein (FIGS. 8A and 8B). In addition, the T cell engagers were constructed to include an LS mutation. Furthermore, the T cell engagers were constructed such that within one binding protein, one C.sub.H3 domain included a knob mutation and the other C.sub.H3 domain included a hole mutation to facilitate heterodimerization of the heavy chains (FIGS. 8A and 8B).

[0602] Using this approach, two T cell engagers were constructed which targeted both T cell surface proteins and the HIV-1 Env glycoprotein (Binding Protein 32 and CD3?CD28/CD4BS b Ab). These two T cell engagers were created by grafting onto a trispecific binding protein framework the V.sub.H and V.sub.L domains isolated from parental antibodies targeting the T cell surface proteins CD3 and CD28, and the anti-HIV-1 antibody CD4BS Ab b (targeting the CD4 Binding Site on gp120). Binding Protein 32 was constructed such that the first pair of polypeptides (which formed two antigen binding sites) targeted the T cell surface receptors CD28 and CD3, and the second pair of polypeptides (which formed the single antigen binding site) targeted the HIV-1 antigen CD4BS (Binding Protein 32=CD28?CD3/CD4BS). The CD3?CD28/CD4BS b Ab trispecific binding protein was constructed such that the first pair of polypeptides (which formed two antigen binding sites) targeted the T cell surface receptors CD3 and CD28, and the second pair of polypeptides (which formed the single antigen binding site) targeted the HIV-1 antigen CD4BS (Table 11).

TABLE-US-00009 TABLE 11 Format of T-cell engagers Arm 1 Arm 2 Arm 3 Format Name of Construct Antigen Antigen Antigen T cell engagers, CD3 ? CD28/CD4BS CD4BS CD3 CD28 trispecific Ab b T cell engagers, Binding Protein 32 CD4BS CD28 CD3 trispecific Monospecific CD4BS IgG4 CD4BS CD4BS

[0603] The ability of the two T cell engagers to bind to each of their three target antigens was tested by ELISA assay. The T cell engagers were capable of binding both the CD3 and CD28 T cell surface proteins with the CD3 and CD28 antigen binding sites in either orientation in the bispecific arms of the T cell engagers (i.e., CD3?CD28 for CD3?CD28/CD4BS Ab b or CD28?CD3 for Binding Protein 32). Both T cell engagers were also capable of binding to gp120 (as measured using the HIV-1 RSC3 protein, a gp120 variant lacking the V1, V2, and V3 variable regions) (FIG. 9).

[0604] The effect on T cell activity was next tested for both of the T cell engagers. Incubation of the T cell engagers with monocytes revealed that the T cell engagers induced robust CD8.sup.+ T cell activation (FIG. 10). Similarly, the T cell engagers were capable of inducing significant CD4.sup.+ T cell activation on PBMCs alone, or PBMCs incubated with either of the HIV-1 infected T cell lines CEM-NKr cells or CEM-BaL cells (FIG. 11). Additionally, both of the T cell engagers reduced cell surface expression of CD3 on activated T cells (FIG. 12).

[0605] Finally, the ability of the T cell engagers to induce lysis of HIV-infected cells was tested. The T cell engagers (and positive and negative control bispecific binding proteins targeting CD3 and an HIV antigen) were incubated with the HIV-1 infected T cell line CEM-BaL cells. Incubation of the T cell engagers with the infected cells induced robust cell lysis over a wide range of concentrations (FIG. 13A). Likewise, incubation of these T cell engagers induced lysis of the latently infected T cell line ACH2 cells (FIG. 13B), as well as J1.1 cells (FIG. 13C). Surprisingly, the T cell engagers showed comparable or better cytotoxic activity against chronic and latent HIV-infected cell lines when compared to the bispecific binding proteins.

[0606] Taken together, the novel T cell engagers described herein retained the ability from their parental antibodies to bind their target antigens on the HIV-1 Env glycoprotein gp120 on HIV-infected cells, as well as the cell-surface exposed T cell proteins CD3 and CD28. The T cell engagers induced robust CD4.sup.+ and CD8.sup.+ T cell activation, and diminished CD3 surface expression. Finally, these T cell engagers induced significant lysis of HIV-1 infected T cells. Without wishing to be bound by theory, these T cell engagers may provide a novel strategy for anti-viral therapeutics by reducing/eliminating the latent viral reservoir through T cell engagement in HIV/AIDS patients.

[0607] While the present disclosure includes various embodiments, it is understood that variations and modifications will occur to those skilled in the art. Therefore, it is intended that the appended claims cover all such equivalent variations that come within the scope of the disclosure. In addition, the section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0608] Each embodiment herein described may be combined with any other embodiment or embodiments unless clearly indicated to the contrary. In particular, any feature or embodiment indicated as being preferred or advantageous may be combined with any other feature or features or embodiment or embodiments indicated as being preferred or advantageous, unless clearly indicated to the contrary.

[0609] All references cited in this application are expressly incorporated by reference herein.

SEQUENCES

[0610]

TABLE-US-00010 TABLE 1 Heavy and light chain SEQ ID NOs for binding proteins 1-53 and the target antigens to which the binding proteins are directed. Binding Protein SEQ ID NOs Target 1 4, 3, 1, 2 MPER ? V1/V2 directed/CD4BS 2 12, 11, 9, 10 MPER ? V1/V2 directed/CD4BS 3 20, 9, 17, 18 V1/V2 directed ? MPER/CD4BS 4 28, 27, 25, 26 MPER ? V1/V2 directed/CD4BS 5 36, 35, 33, 34 MPER ? V3 directed/CD4BS 6 44, 43, 41, 42 V1/V2 directed ? MPER/CD4BS 7 52, 51, 49, 50 V3 directed ? V1/V2 directed/CD4BS 8 60, 59, 57, 58 MPER ? V1/V2 directed/CD4BS 9 68, 67, 65, 66 MPER ? V1/V2 directed/CD4BS 10 76, 75, 73, 74 V1/V2 directed ? MPER/CD4BS 11 84, 83, 81, 82 MPER ? V1/V2 directed/CD4BS 12 92, 91, 89, 90 MPER ? V3 directed/CD4BS 13 100, 99, 97, 98 MPER ? V3 directed/V1/V2 directed 14 108, 107, 105, 106 V1/V2 directed ? MPER/CD4BS 15 116, 115, 113, 114 MPER ? V3 directed/V1/V2 directed 16 124, 123, 121, 122 MPER ? V3 directed/CD4BS 17 132, 131, 129, 130 V1/V2 directed ? V3 directed/CD4BS 18 140, 139, 137, 138 V3 directed ? MPER/CD4BS 19 148, 147, 145, 146 V3 directed ? V1/V2 directed/MPER 20 156, 155, 153, 154 V3 directed ? V1/V2 directed/CD4BS 21 164, 163, 161, 162 MPER ? CD4BS/V1/V2 directed 22 172, 171, 169, 170 CD4BS ? MPER/V1/V2 directed 23 180, 179, 177, 178 CD4BS ? V1/V2 directed/MPER 24 188, 187, 185, 186 V1/V2 directed ? CD4BS/MPER 25 196, 195, 193, 194 MPER ? V1/V2 directed/CD4BS 26 204, 203, 201, 202 MPER ? V1/V2 directed/CD4BS 27 212, 211, 209, 210 MPER ? V1/V2 directed/CD4BS 28 220, 219, 217, 218 MPER ? V1/V2 directed/CD4BS 29 228, 227, 225, 226 MPER ? V1/V2 directed/CD4BS 30 235, 234, 232, 233 MPER ? V1/V2 directed/CD4BS 31 243, 242, 240, 241 MPER ? V1/V2 directed/CD4BS 32 305, 304, 302, 303 CD28 ? CD3/CD4BS 33 313, 312, 310, 311 CD28 ? CD3/CD4BS 34 321, 320, 318, 319 CD28 ? CD3/V1/V2 directed 35 329, 328, 326, 327 CD28 ? CD3/V1/V2 directed 36 337, 336, 334, 335 CD28 ? CD3/CD4BS 37 345, 344, 342, 343 CD28 ? CD3/CD4BS 38 353, 352, 350, 351 CD4BS ? CD3/CD28 39 361, 360, 358, 359 CD4BS ? CD3/CD28 40 369, 368, 366, 367 CD3 ? CD4BS/CD28 41 377, 376, 374, 375 CD3 ? CD4BS/CD28 42 385, 384, 382, 383 CD4BS ? CD3/CD28 43 393, 392, 390, 391 CD4BS ? CD3/CD28 44 401, 400, 398, 399 CD3 ? CD4BS/CD28 45 409, 408, 406, 407 CD3 ? CD4BS/CD28 46 417, 416, 414, 415 V1/V2 directed ? CD3/CD28 47 425, 424, 422, 423 V1/V2 directed ? CD3/CD28 48 433, 432, 430, 431 CD3 ? V1/V2 directed/CD28 49 441, 440, 438, 439 CD3 ? V1/V2 directed/CD28 50 449, 448, 446, 447 V1/V2 directed ? CD3/CD28 51 457, 456, 454, 455 V1/V2 directed ? CD3/CD28 52 465, 464, 462, 463 CD3 ? V1/V2 directed/CD28 53 473, 472, 470, 471 CD3 ? V1/V2 directed/CD28

TABLE-US-00011 TABLE2 Heavyandlightchainsequencesofbindingproteins.CDRsequencesare boldedanditalicized. BindingProtein1AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyef wirlapgkrpewmg SEQID rvtmtrdvysdtaflelrsltvddtavyfctr NO:1 wgrgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalt sgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtimisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreegynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainA Eivltqspgtlslspgetaiisc wqqrpgqaprlviy gipdrf SEQID sgsrwgpdynltisnlesgdfgvyyc fgqgtkvqvdiktrtvaapsvfifpps NO:2 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrtvesggglvkpggslrlscsas mtwvrqppgkglewvgr SEQID dyaesvkgrftisrdntkntlylemnnvrtedtgyyfcar NO:3 wgqgtlvivssdkthtqvhltqsgpevrkpgtsvkvsckapgntlktyd lhwvrsvpgqglqwmgwishegdkkviverfkakvtidwdrstntaylqlsgltsg dtavyy gqgtavtvssdkt htastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglysissvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcp apellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevh naktkpreegynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakg qprepqvytlppcrdeltknqvslwclvkgfypsdiavewesngqpennykttpp vldsdgsfflyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB Dfvltqsphslsvtpgesasisckss lawyvqkpgrspqlliy s SEQID rasgvpdrfsgsgsdkdftlkisrvetedvgtyyc gqgtkvdikdkt NO:4 ht aseltqdpavsvalkqtvtitc wyqkkpgqapvllfy gi pdrfsgsasgnrasltitgaqaedeadyyc fgggtkltvldkthtrtv aapsvfifppsdeqlksgtusvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein1NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcg SEQID gatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcaga NO:5 ctggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttct gcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcgcgtcgaccaagggccccagcgtgttccctctggccc ctagcagcaagageacatctggcggaacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgaca gtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagccca gcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggt ggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtg caaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccgg tggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA Gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacaac SEQID catcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcc NO:6 tggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatcc ccgatagattcagcggctccagatggggccctgactacaacctgaccatcagcaacct ggaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggc accaaggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcc cacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaa cttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcg gcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctg cgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctgaataacctgggtcaggcag NO:7 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgaggactg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagaigaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggtg tcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcagc gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaaga aagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcacca acaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtactactg cgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcg ccctgaactgggccgtggatgtggactacctgagcaacctagaattctggggccaggg cacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagggcccatcg gtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggct gcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgccct gaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctca gcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgt gaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagt cttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:8 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcatgcccgatagattttctggcageggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaaggacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccg gcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagt ccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagt gcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein2AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgyfftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:9 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtvicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvscsvlhealhshytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:10 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadvekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:11 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsv kvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkak vtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwav dvdylsnlefwgygtavtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdt lmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynsty rvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlp pcrdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgs fflyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:12 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein2NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:13 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcac acctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagt gcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:14 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatc tgcaggccgacgacattgccacctactattgtcaggtgctgcagttcacggcagaggc agcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctag cgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacag ccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagca ccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtga cccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:15 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacatgagaactaaaaacaccggatattacttct gtgccagaacaggcaaatactacgacttgtggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggtg tcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcagc gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaaga aagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcacca acaccgcctacctgcagctgagcggcctaacctctggcgataccgccgtgtactactg cgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcg ccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccaggg cacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagggcccatcg gtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggct gcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgccct gaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctca gcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgt gaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagt cttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtatggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:16 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaaggacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccg gcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagt ccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagt gcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein3AminoAcidSequences HeavychainA rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqyg SEQID avnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswaldaw NO:17 gqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:18 glksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmg SEQID wishegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgsk NO:19 hrlrdyalydddgalnwavdvdylsnlefwgqgtavtvssdkthtevrlves ggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgpgeg wsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyydfws gyppgeeyfqdwgqgtlvivssdkthtastkgpsvfplapsskstsggtaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqt yicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpk dtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyns tyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvyt lppcrdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsd gsfflyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB aseltqdpavsvalkqtvtitcrgdsltshyaswyqkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtdfvlt NO:20 qsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassrasgv pdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkthtrtva apsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqds kdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein3NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtatcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:21 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcac acctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagt gcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:22 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatc tgcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggc agcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctag cgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacag ccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagca ccctgacactgagcaaggccgactacgagaaacacaaggtgtacgcctacgaagtga cccaccagggcctatctagccccgtgaccaagagatcaaccagggcgagtgt HeavychainB caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctct SEQID gtgaaggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgca NO:23 ctgggtgcgcagcgtgccaggacagggactgcagtggatgggctggatcag ccacgagggcgacaagaaagtgatcgtggaacggttcaaggccaaagtgac catcgactgggacagaagcaccaacaccgcctacctgcagctgagcggcctg acctctggcgataccgccgtgtactactgcgccaagggcagcaagcaccggc tgagagactacgccctgtacgacgatgacggcgccctgaactgggccgtgga tgtggactacctgagcaacctggaattaggggccagggcacagccgtgacc gtgtcatctgacaaaacccataccgaggttagactggtggagtcaggaggggg gcttgtgaagcccggtgggtctctccgcctgagagttctgcctccggctttgatt tcgataacgcctggatgacctgggtcaggcagcaccaggtaagggactgga gtgggtgggaagaatcacaggtccaggcgagggctggtccgtggactacgc ggaatctgttaaagggcggtttacaatctcaagggacaataccaagaataccttg tatttggagatgaacaacgtgagaactgaagacaccggatattacttctgtgcca gaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatattt tcaagactggggtcagggaacccttgttatcgtgtcctccgataagacccacac cgcttccaccaagggcccatcggtcttccccctggcaccctcctccaagagcac ctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaac cggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacacctt cccggctgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgt gccctccagcagcttgggcacccagacctacatagcaacgtgaatcacaagc ccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtgacaaaact cacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtctt cctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggt cacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaact ggtatgttgacggcgtggaggtgcataatgccaagacaaagccgcgggagga gcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccagg actggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctccca gcccccatcgagaaaaccatctccaaagccaaagggcagccccgagaacca caggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtggga gagcaatgggcagccggagaacaactacaagaccacgcctcccgtgctgga ctccgacggctccttcttcactactcaaaactcaccgtggacaagagcaggtg gcagcaggggaacgtatctcatgctccgtgctgcatgaggctctscacagcc actacacgcagaagagcctctccctgtctccgggt LightchainB gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgtgactat SEQID tacttgccgaggcgactcactgcggagccactacgcttcctggtatcagaagaaaccc NO:24 ggccaggcacctgtgctgctgttctacggaaagaacaataggccatctggcatccccg accgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccggcgccca ggctgaggacgaagccgattactattgcagctcccaggataaaagcggctccagact gagcgtgttcggaagaggaactaaactgaccgtcctcgacaaaacccataccgacttc gtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccagcatc agctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttggt acgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagag ccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaa gatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagag agagcccctggacctttgaccagggcaccaaggtggacatcaagaataagacccata cccgtacaatggccgctcccagcgtgacatcttcccacctagcgacgagcagctgaa gtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaa gtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtga ccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagc aaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcct gtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein4AminoAcidSequences HeavychainA qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:25 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevhnaktkpreegynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrf SEQID sgsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifpps NO:26 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgri SEQID tgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:27 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqvhltqgpevrkpgts vkvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfka kvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwa vdvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqt yicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpk dtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyns tyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvyt lppcrdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsd gsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:28 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein4NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcg SEQID gatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcaga NO:29 ctggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttct gcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcatcgaccaagggccccagcgtgttccctctggccc ctagcagcaagagcacatctgacggaacagccgccagggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgaca gtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagccca gcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccgaacccccgaagtgacctgcatggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacatggacgacgtggaa gtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggt ggtgtccgtgctgaccgtgagcaccaggactggctgaacggcaaagagtacaagtg caaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccagatgtccctgagagtaccatgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccgg tggcagcagggcaacgtgttcagagaccgtgatgcacgaggccctgcacaaccact acacccagaagtccagagcctgagccccggc LightchainA Gagatcgtgctgacacagagccaggcaccctgagcctgtctccaggcgagacagc SEQID catcatcagtgccggacaagccagtacggcagcctggcctggtatcagcagaggcc NO:30 tggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatcc ccgatagattcagcggctccagatggggccagactacaacctgaccatcagcaacct ggaaagcgacgacttcgacgtgtactactgccagcaatacgagttcttcggccagggc accaaggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcc cacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaa cttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcg gcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctg cgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggagaggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:31 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca ggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggt gtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcag cgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaag aaaggatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcacc aacaccgcctacctacaactgagcggcctaacctctggcgataccgccgtgtactact gcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggc gccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccagg gcacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagggcccatc ggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctggg ctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgcc ctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccct cagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaac gtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtg acaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcag tcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtagaggtgcataataccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatagcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaattggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccgaaacaactacctg NO:32 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaaggacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctagtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccg gcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagt ccggcacagcctctatcgtgtgcctgctgaacaacttctacccccgcgaggccaaagt gcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein5AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:33 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyggrpgqaprlviysgstraagipdrfs SEQID gsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsd NO:34 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:35 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqmqlqesgpglvkpse tlsltcsvsgasisdsywswirrspgkglewigyvhksgdtnyspslksrvnl sldtsknqvslslvaataadsgkyycartlhgrriygivafnewftyfymdvw gngtqvtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtv swnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntk vdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcv vvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqd wlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltknqv slwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdks rwqqgnvfscsvmhealhnhytqkslslspg LightchainB Sdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtaseltqdp NO:36 avsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgsas gnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfifp psdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysls stltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein5NucleotideSequences HeavychainA Caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgc SEQID ggatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcag NO:37 actggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggag ccgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtaca gcgataccgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttc tgcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagagg cacccctgtgatcgtgtcaagc gcgtcgaccaagggccccagcgtgttccctctggcccctagcagcaagagcacatct ggcggaacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgacc gtgtcctagaattctgacgccctgaccagcggcgtgcacacctttccagctgtgctgca gtccagcggcctgtacagcctgagcagcgtcgtgacagtgcccagcagctctctggg cacccagacctacatctgcaacgtgaaccacaagcccagcaacaccaaggtggacaa gaaggtggaacccaagagctgcgacaagacccacacctgtcccccttgtcctgcccc cgaactgctgggaggcccttccgtgttcctgttccccccaaagcccaaggacaccctg atgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccacgaggac cctgaagtgaagttcaattggtacgtggacggcgtggaagtgcacaacgccaagacca agccaagagaggaacagtacaacagcacctaccgggtggtgtccgtgctgaccgtgc tgcaccaggactggctgaacggcaaagagtacaagtgcaaggtatccaacaaggccc tgcctgcccccatcgagaaaaccatcagcaaggccaagggccagccccgcgaaccc caggtgtgcacactgcccccaagcagggacgagctgaccaagaaccaggtgtccctg agctgtgccgtgaaaggcttctacccctccgatatcgccgtggaatgggagagcaacg gccagcccgagaacaactacaagaccaccccccctgtgctggacagcgacggctcat tcttcctggtgtccaaactgacagtggacaagtcccggtggcagcagggcaacgtgttc agctctccgtgatgcacgaggccctgcacaaccactacacccagaagtccctgagc ctgagccccggc LightchainA Gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagc SEQID catcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcc NO:38 tggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatcc ccgatagattcagcggctccagatggggccctgactacaacctgaccatcagcaacct ggaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggc accaaggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcc cacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaa cttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcg gcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctg cgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccagtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:39 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcaaggaacccttgttatcgtgtcctccgacaaaacccataccca gatacagctgcaggagagcggccctggactcgtgaagcccagcgagaccctgaacc tgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcagga ggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgacacc aactacagcccctccctgaagtccagggtgaacctgtccctggacaccagcaagaacc aggtgagcctgtccctggtggctgccacagctgctgacagcggcaagtactactgtgc caggaccctgcacggcaggaggatctacggcatcgtggccttcaacgagtggttcacc tacttctacatggacgtgtggggcaacggcacccaggtgaccgtgagctccgataaga cccacaccgcttccaccaagggcccatcggtcttccccctggcaccctcctccaagag cacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaacc ggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggc tgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagca gcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggt ggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccaccgtgccca gcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaaggaca ccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacga agaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgccaaga caaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctcacc gtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaa gccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccgaga accacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagc aatgggcagccggagaacaactacaagaccacgcctcccgtgctggactccgacgg ctccttcttcctctactcaaaactcaccgtggacaagagcaggtggcagcaggggaac gtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgcagaagagcct ctccctgtctccaggt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgagaagag SEQID cctgggaagcagggctgtgcagtagtaccaacacagggccggacaggctcccagcc NO:40 tgatcatctacaacaaccaggacaggcccagcggcatccctgagaggttcagcggaa gccccgacagccccttcggaaccacagccaccctgaccatcacaagcgtggaagcc ggcgacgaggccgactactactgccacatctgggacagcagggtgcccaccaagtg ggtgtttggcggcggcaccaccctgaccgtgctggacaaaacccataccgcatccga actgactcaggaccctgccgtctctgtggcactgaagcagactgtgactattacttgccg aggcgactcactgcggagccactacgcttcctggtatcagaagaaacccggccaggc acctgtgctgctgttctacggaaagaacaataggccatctggcatccccgaccgcttttc tggcagtgcatcagggaaccgagccagtctgaccattaccggcgcccaggctgagga cgaagccgattactattgcagctcccgggataagagcggctccagactgagcgtgttc ggaggaggaactaaactgaccgtcctcgataagacccatacccgtacggtggccgct cccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgt cgtgtgcctgagaacaacttctacccccgcgaggccaaagtgcagtggaaggtggac aacgccctgcagagcggcaacaaccaggaaagcgtgaccgagcaggacagcaag gactccacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaag agcttcaaccggggcgagtgt BindingProtein6AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:41 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfs SEQID gsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsd NO:42 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmg SEQID wishegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgsk NO:43 hrlrdyalydddgalnwavdvdylsnlefwgqgtavtvssdkthtevrlves ggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgpgeg wsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyydfw wgyppgeeyfqdwgqgtlvivssdkthtastkgpsvfplapsskstsggtaa lgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgt qtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppk pkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqy nstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepq vytlppcrdeltknqvstwclvkgfypsdiavewesngqpennykttppvl dsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB Aseltqdpavsvalkqvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi SEQID pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtdfv NO:44 ltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassrasg vpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqatkvdikdkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein6NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcg SEQID gatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcaga NO:45 ctggcccctggcaaacggcctgagtggatgggatggctgaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttct gcacccggggcaagaactgegactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcgtcgaccaagggccccagcgtgttccctctggccc ctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgaca gtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagccca gcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccgaacccccgaagtgacctgcgtggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacatggacgacgtggaa gtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggt ggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtg caaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccaggtgtccctgagctgtgccatgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccgg tggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccggc LightchainA gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagcc SEQID atcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcct NO:46 ggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccc cgatagattcagcggctccagatggggccctgactacaacctgaccatcagcaacctg gaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggca ccaaggtgcaggtggacatcaagcgtacggtggccgctcccagcatgttcatcttccc acctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaac ttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctga gcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgc gaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB caggtgcacctgacacaaagcggacccgaagtgcggaagcctagcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:47 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggcc agggcacagccgtgaccgtgtcatctgacaaaacccataccgaggttagactggtgga gtcaggaggggggcttgtgaagcccggtgggtctctccgcctgagctgttctgcctcc ggctttgatttcgataacgcctggatgacctgggtcaggcagcctccaggtaagggact ggagtgggtgggaagaatcacaggtccaggcgagggctggtccgtggactacgcgg aatctgttaaagggcggtttacaatctcaagggacaataccaagaataccttgtatttgga gatgaacaacgtgagaactgaagacaccagatattacttctgtgccagaacaggcaaa tactacgacttctggtggggctatccccctggcgaggaatattttcaagactggggtcag ggaacccttgttatcgtgtcctccgataagacccacaccgcttccaccaagggcccatc ggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctggg ctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgcc ctgaccagcggcgtgcaccttcccggctcgtcctacagtcctcaggactctactccct cagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaac gtgaatcacaagcccagcaacaccaaggtgaacaagaaagttgagcccaaatcttgtg acaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcag tcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctct gcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB Gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgt SEQID gactattacttgccgaggcgactcactgcggagccactacgcttcctggtatca NO:48 gaagaaacccggccaggcacctgtgctgctgttctacggaaagaacaatagg ccatctggcatccccgaccgcttttctggcagtgcatcagggaaccgagccagt ctgaccattaccggcgcccaggctgaggacgaagccgattactattgcagctc ccgggataagagcggctccagactgagcgtgttcggaggaggaactaaactg accgtcctcgacaaaacccataccgacttcgtgctgacccagagccctcacag cctgagcgtgacacctggcgagagcgccagcatcagctgcaagagcagcca ctccctgatccacggcgaccggaacaactacctggcttggtacgtgcagaagc ccggcagatccccccagctgctgatctacctggccagcagcagagccagcgg cgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaagat cagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcaga gagagcccctggacctttggccagggcaccaaggtggacatcaaggataaga cccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacg agcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggc aacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagc ctgagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgt acgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttc aaccggggcgagtgt BindingProtein7AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:49 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfs SEQID gsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsyfifppsd NO:50 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB qmqlqesgpglvkpsetlsltcsvsgasisdsywswirrspgkglewigyvh SEQID ksgdtnyspslksrvnlsldtsknqvslslvaataadsgkyycartlhgrriygi NO:51 vafnewftyfymdvwgngtqvtvssdkthtQvhltqsgpevrkpgtsvkv sckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkakvti dwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwavdv dylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgclvk dyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicn vnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlm isrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrv vsvltvlhqdwlngkeykekvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsf flyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB Dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:52 tsdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgs pdspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein7NucleotideSequences HeavychainA caggtgcagaggtgcagtctggcggccagatgaagaaacccggcgagagcatacg SEQID gatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcaga NO:53 ctggcccctggcaagcggcctgagtggatgggatggagaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccgcctcctggaactgcggagcctgaccgtggatgataccgccgtgtacttct gcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcgtcgaccaagggccccagcgtgttccctctggccc ctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagagtgagcagtccagcggcctgtacagcctgagcagcgtcgtgaca gtacccagcagctactgagcacccagacctacatctgcaacgtgaaccacaagccca acaacaccaaggtagacaagaaggtgaaacccaagagctacgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggt ggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtg caagatgtccaacaaggccctgcctacccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccgg tggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccggc LightchainA gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagcc SEQID atcatcagagccggacaagccagtacggcagcctagcctggtatcaacagaggcct NO:54 ggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccc cgatagattcagcggaccagatggggccctgactacaacctgaccatcagcaacctg gaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggca ccaaggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttccc acctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaac ttctacccccgcgaggccaaagtgcagtggaaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctga gcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgc gaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB cagatgcagctgcaggagagcggccctggactcgtgaagcccagcgagaccctgag SEQID cctgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcag NO:55 gaggagccctggcaagggcctggagtggatcggctacgtgcacaagagcgacgac accaactacagcccctccctgaagtccagggtgaacctgtccctggacaccagcaaga accaggtgagcctgtccctggtggctgccacagctgctgacagcggcaagtactactg tgccaggaccctgcacggcaggaggatctacggcatcgtggccttcaacgagtggttc acctacttctacatggacgtggggcaacggcacccaggtgaccgtgagctccgaca aaacccatacccaggtgcacctgacacagagcggacccgaagtgcggaagcctggc acctagtgaagatgtcctgcaagacccaggcaacaccctgaaaacctacgacctgc actgggtgcgcagcgtgccaggacagggactgcagtggatgggctggatcagccac gagggcgacaagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgg gacagaagcaccaacaccgcctacctgcagctgagcggcctgacctctggcgatacc gccgtgtactactgcgccaagggcagcaagcaccggctgagagactacgccctgtac gacgatgacggcgccctgaactgggccgtggatgtggactacctgagcaacctggaa ttctgaggccaggacacaaccatgaccatgtcatctgataagacccacaccgcttcca ccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcac agcggccctgggctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtgg aactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcag gactctactccctcagcagcgtggtgaccgtgccctccagcttgcttgggcacccagac ctacatagcaacgtgaatcacaagcccagcaacaccaaggtgaacaagaaagttga gcccaaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactcagg ggggaccgtcagtcttcctcttccccccaaaacccaaggacaccctcatgatctcccgg acccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaag ttcaactggtatgttgacggcgtggaggtgcataatgccaagacaaagccgcgggagg agcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactg gctgaatggcaaggaatacaagtgcaaggtctccaacaaagccctcccagcccccat cgagaaaaccataccaaagccaaagggcagccccgagaaccacaggtgtacaccc tgcccccatgccgaaataagctgaccaaaaatcaagtcagcctgtggtacctggtaaa aggctctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggaga acaactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctactcaa aactcaccgtggacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgat gcatgaggctctgcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB Gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgaga SEQID gcgccagcatcagctgcaagagcagccactccctgatccacggcgaccggaa NO:56 caactacctggcttggtacgtgcagaagcccggcagatccccccagctgctga tctacctggccagcagcagagccagcggcgtgcccgatagattttctggcagc ggcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgaggac gtgggcacctactactgtatgcagggcagagagagcccctggacctttggcca gggcaccaaggtggacatcaaggacaaaacccatacctccgacatcagcgtg gcccccggagagacagccaggatctcctgcggcgagaagagcctgggaag cagggctgtgcagtggtaccaacacagggccggacaggctcccagcctgatc atctacaacaaccaggacaggcccageggcatccctgagaggttcagcggaa gccccgacagccccttcggaaccacagccaccctgaccatcacaagcgtgga agccggcgacgaggccgactactactgccacatctgggacagcagggtgcc caccaagtgggtgtttggcggcggcaccaccctgaccgtgctggataagaccc atacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagc agctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaac agccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtac gcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaa ccggggcgagtgt BindingProtein8AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:57 wgqgttvvvsaastkapsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi cktiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsffvskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainA Yihvtqspsslsvsigdrvtincqtsqvgsdlhwyqhkpgrapkllihhtssvedg SEQID vpsrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsd NO:58 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksthrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqpgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:59 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqvqlvesgggvvqpgt slrlscaasqfrfdgygmhwvrqapgkglewvasishdgikkyhaekvwg rftisrdnskntlylqmnslrpedtalyycakdlredeceewwsdyydfgkq lpcaksrgglvgiadnwgqgtmvtvssdkthtastkgpsvfplapsskstsg gtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlssglyslssvvtvpss slgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflf ppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpr eeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqpr epqvytlppcrdeltknqvslwelvkgfypsdiavewesngqpennykttp pvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB Qsvltqppsvsaapgqkvtiscsgntsnignnfvswyqqrpgrapqlliyetdkrps SEQID gipdrfsasksgtsgtlaitglqtgdeadyycatwaaslssarvftgtkvivldkthtas NO:60 eltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdr fsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaap svfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdsk dstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein8NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggca NO:61 ggcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccg tgaacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcg agatcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactg cgccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagg gcacaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggc ccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaagg actactttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtg cacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtga cagtacccaacaactctctgggcacccagacctacatagcaacgtgaaccacaagc ccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagaccca cacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggt ggtggatgtgtcccacgaggaccctgaagtgaattcaattggtacgtggacggcgtg gaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctacc gggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtaca agtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaagg ccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacga gctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgat atcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccc cccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaag tcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcac aaccactacacccagaagtccctgagcctgagccccggcaag LightchainA Tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgaca SEQID gagtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactg NO:62 gtatcagcacaagcctggcagagcccccaagctgctgatccaccacacaagc agcgtggaagatggcgtgcccagcagattttccggcagcggcttccacacca gcttcaacctgaccatcagcgatctgcaggccgacgacattgccacctactatt gtcaggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtcc ggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaa agtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaa gcgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccc tgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagt gacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:63 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca ggtgcagttggtggagtctgggggaggcgtggtccagcctgggacgtccctgagact ctcctgtgcagcctctcaattcaggtttgatggttatgacatgcactgggtccgccaggc cccaggcaaggggctggagtgggtggcatctatatcacatgatggaattaaaaagtat cacgcagaaaaagtgtggggccgcttcaccatctccagagacaattccaagaacaca ctgtatctacaaatgaacagcctgcgacctgaggacacggctctctactactgtgcgaa agatttgcgagaagacgaatgtgaagagtggtggtcggattattacgattttgggaaac aactcccttgcgcaaagtcacgcggcggcttggttggaattgctgataactggggcca agggacaatggtcaccgtctcttcagataagacccacaccgcttccaccaagggccca tcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgg gctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgc cctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccc tcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaa cgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgt gacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtca gtcttcctcttccccccaaaacccaaggacaccctcatgatctcccgaacccctgaggt cacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtat gttgacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaa cagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggc aaggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaacc atctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgc cgggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatcc cagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaag accacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtg gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatacatgaggct ctgcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB Cagtctgtgctgacgcagccgccctcagtgtctgcggccccaggacagaagg SEQID tcaccatctcctgactggaaacacctccaacattggcaataattttgtgtcctggt NO:64 atcaacagcgccccggcagagccccecaactcctcatttatgaaactgacaag cgaccctcagggattcctgaccgattctctgcttccaagtctggtacgtcaggca ccctggccatcaccgggctgcagactggggacgaggccgattattactgcgc cacatgggctgccagcctgagttccgcgcgtgtatcggaactgggaccaagg tcatcgtcaggacaaaacccataccgcatccgaactgactcaggaccctgcc gtctctgtggcactgaagcagactgtgactattacttgccgaggcgactcactgc ggagccactacgcttcctggtatcagaagaaacccggccaggcacctgtgctg ctgttctacggaaagaacaataggccatctggcatccccgaccgcttttctggca gtgcatcagggaaccgagccagtctgaccattaccggcgcccaggctgagga cgaagccgattactattgcagctcccgggataagagcggctccagactgagcg tgttcggaggaggaactaaactgaccgtcctcgataagacccatacccgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtcc ggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaa agtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaa gcgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccc tgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagt gacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt BindingProtein9AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:65 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppcpapellggpsvflfppkpkdtlmisrtpevrcvvvdvshedpevkfnwyv dgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakaqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfs SEQID gsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsd NO:66 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqpgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:67 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqvqlvesgggvvqpgt slrlscaasqfrfdgygmhwvrqapgkglewvasishdgikkyhaekvwg rftisrdnskntlylqmnslrpedtalyycakdlredeceewwsdyydfgkq lpcaksrgglvgiadnwgqgtmvtvssdkthtastkgpsvfplapsskstsg gtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpss slgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflf ppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpr eeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqpr epqvytlppcrdeltknqvslwclvkgfypsdiavewesngqpennykttp pvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB qsvltqppsvsaapgqkvtiscsgntsnignnfvswyqqrpgrapqlliyetdkrps SEQID gipdtgsasksgtsgtlaitglqtgdeadyycatwaaslssarvfgtgtkvivldkthtas NO:68 eltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdr fsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaap svfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdsk dstyslsstlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein9NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcg SEQID gatcagctgcagagccagcggctacgagttcatcgadgcaccctgaactggatcaga NO:69 ctggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccaccttcctagaactacgaagcctgaccgtagatgataccgccgtgtacttct gcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcgtcgaccaagggccccagcgtgttccctctggccc ctagcagcaagageacatctggcggaacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagctgtactacagtccagcggcctgtacaacctgagcagcgtcgtgaca gtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagccca gcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaa gtacacaacaccaagaccaagccaagagaggaacagtacaacageacctaccggat ggtgtccgtgctgaccgtgctgcaccaggactgactgaacggcaaagagtacaagtg caaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgaggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccgg tggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccggc LightchainA gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagcc SEQID atcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcct NO:70 ggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccc cgatagattcagcggaccagatggggccctgactacaacctgaccatcagcaacctg gaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggca ccaagatgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttccc acctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaac ttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctga gcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgc gaagtgacccaccagggcctgtctagccccatgaccaagagatcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctaccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:71 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacatgagaactgaagacaccggatattacttct gtaccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca ggtgcagttggtggagtctgggggaggcgtggtccagcctgggacgtccctgagact ctcctgtgcagcctctcaattcaggtttgatggttatggcatgcactgggtccgccaggc cccaggcaaggggctggagtgggtggcatctatatcacatgatggaattaaaaagtatc acgcagaaaaagtgtagggccgcttcaccatctccagagacaattccaagaacacact gtatctacaaataaacaacctgcgacctgaggacacggctctctactactgtgcgaaag atttgcgagaagacgaatgtgaagagtggtggtcggattattacgattttgggaaacaac tcccttgcgcaaagtcacgcggcggcttggttggaattgctgataactggggccaagg gacaatggtcaccgtacttcagataagacccacaccgcttccaccaagggcccatcg gtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggct gcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgccct gaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctca gcagcgtggtgaccgtaccctccagcagcttgggcacccagacctacatctgcaacgt gaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagt cttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctgaactccgacggctccttatcctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctct gcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB cagtctgtgctgacgcagccgccctcagtatctgcgaccccaggacagaaggtcacc SEQID atctcctgactggaaacacctccaacattggcaataattttgtgtcctggtatcaacagc NO:72 gccccggcagagccccccaactcctcatttatgaaactgacaagcgaccctcagggat tcctgaccgattctctgcttccaagtctggtacgtcaggcaccetggccatcaccgggct gcagactggggacgaggccgattattactgcgccacatgggctgccagcctgagttcc gcgcgtgtcttcggaactgggaccaaggtcatcgtcctg gacaaaacccataccgcatccgaactgactcaggaccctgccgtctctgtggcactga agcagactgtgactattacttgccgaggcgactcactgcggagccactacgcttcagg tatcagaagaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggc catctggcatccccgaccgcttttaggcagtacatcagggaaccgagccagtctgacc attaccggcacccaaactgaggacgaagccaattactattgcaactcccgggataaga gcggctccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagac ccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcag ctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggc caaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagc gtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacact gagcaaggccgactacgagaagcacaagatgtacacctgcgaagtgacccaccagg gcctatctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein10AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkpr SEQID ggavnyarplqgrvtmtrdvysdtaflelrsltvddtavyfctrgkncdynwdfehw NO:73 grgtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkt htcppepapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyv dgvevnnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiekt iskakaqprepqvctlppsrdeltknqvslscavkgypsdiavewesngqpenny kttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfs SEQID gsrwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsd NO:74 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB qvqlvesgggvvqpgtslrlscaasqfrfdgygmhwvrqapgkglewvas SEQID ishdgikkyhaekvwgrftisrdnskntlylqmnslrpedtalyycakdlred NO:75 eceewwsdyydfgkqlpcaksrgglvgiadnwgqgtmvtvssdkthtevr lvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgp gegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyyd fwwgyppgeeyfqdwgqgtlvivssdkthtastkgpsvfplapsskstsgg taalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsss lgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfp pkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpree qynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqpre pqvytlppcrdeltknqvslwclvkgfypsdiavewesngqpennykttpp vldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB aseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtqsvlt NO:76 qppsvsaapgqkvtiscsgntsnignnfvswyqqrpgrapqlliyetdkrpsgipdr fsasksgtsgtlaitglqtgdeadyycatwaaslssarvfgtgtkvivldkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein10NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcg SEQID gatcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcaga NO:77 ctggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagc cgtgaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacag cgataccgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttct gcacccggggcaagaactgcgactacaactgggacttcgagcactggggcagaggc acccctgtgatcgtgtcaagcgcgtcgaccaagggccccagcgtgttccctctggccc ctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgca cacctttccagctgtgctgcagtccagcggcctgtacaacctgagcagcgtcgtgaca gtacccagcagctctctgagcacccagacctacatctgcaacgtgaaccacaagccc agcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccaca cctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccc caaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtg gtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtgg aagtacacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccg ggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaa gtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggc caagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgag ctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatat cgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccc cctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtc ccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaa ccactacacccagaagtccctgagcctgagccccggc LightchainA gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagcc SEQID atcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcct NO:78 ggacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccc cgatagattcagcggctccagatggggccctgactacaacctgaccatcagcaacctg gaaagcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggca ccaaggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttccc acctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaac ttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctg cgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcg agtgt HeavychainB caggtgcagttggtggagtctgggggaggcgtggtccagcctgggacgtccctgaga SEQID ctctcctgtgcagcctctcaattcaggtttgatggttatggcatgcactgggtccgccag NO:79 gccccaggcaaggggctggagtgggtggcatctatatcacatgatggaattaaaaagt atcacgcagaaaaagtgtggggccgcttcaccatctccagagacaattccaagaacac actgtatctacaaatgaacagcctgcgacctgaggacacggctctctactactgtgcga aagatttgcgagaagacgaatgtgaagagtggtggtcggattattacgattttgggaaa caactcccttgcgcaaagtcacgcggcggcttggttggaattgctgataactggggcc aagggacaatggtcaccgtctcttcagacaaaacccataccgaggttagactggtgga gtcaggaggggggcttgtgaagcccggtgggtctctccgcctgagctgttctgcctcc ggctttgatttcgataacgcctggatgacctgggtcaggcagcctccaggtaagggact ggagtgggtgggaagaatcacaggtccaggcgagggctggtccgtggactacgcgg aatctgttaaagggcggtttacaatctcaagggacaataccaagaataccttgtatttgga gatgaacaacgtgagaactgaagacaccggatattacttctgtgccagaacaggcaaa tactacgacttctggtccggctatccccctggcgaggaatattttcaagactggggtcag ggaacccttgttatcgtgtcctccgataagacccacaccgcttccaccaagggcccatc ggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctggg ctacctggtcaaggactacttccccgaaccggtgacggtatcatggaactcaggcgcc ctgaccagcagcgtgcacaccttcccggctgtcctacagtcctcaggactctactccct cagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaa cgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgt gacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtca gtcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggt cacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtat gttgacggcgtggaggtgcataataccaagacaaagccgcgggaggagcagtacaa cagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggc aaggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaacc atctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgc cgggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatcc cagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaag accacgcctcccgtgctgaactccgaeggctcatatcctctactcaaaactcaccatg gacaagaacaggtgacaacaagggaacatcttctcataaccatgatgcataaggct ctacacaaccactacacgcagaagaacctaccagtaccgggt LightchainB gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgt SEQID gactattacttgccgaggcgactcactgcggagccactacgcttcctggtatca NO:80 gaagaaacccggccaggcacctgtgctgctgttctacggaaagaacaatagg ccatctggcatccccgaccgctatctggcagtgcatcagggaaccgagccagt ctgaccattaccggcgcccaggctgaggacgaagccgattactattgcagctc ccgggataagagcggctccagactgagcgtgttcggaggaggaactaaactg accgtcctcgacaaaacccatacc cagtctgtgctgacgcagccgccctcagtgtctgcggccccaggacagaagg tcaccatctcctgctctggaaacacctccaacattggcaataattttgtgtcctggt atcaacagcgccccggcagagccccccaactcctcatttatgaaactgacaag cgaccctcagggattcctgaccgattctctgcttccaagtctggtacgtcaggca ccctggccatcaccgggctgcagactggggacgaggccgattattactgcgc cacatgggctgccagcctgagttccgcgcgtgtcttcggaactgggaccaagg tcatcgtcctg gataagacccatacccgtacggtggccgctcccagcgtgacatcttcccacct agcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaa cttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcag agcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccac ctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagca caaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgacc aagagcttcaaccggggcgagtgt BindingProtein11AminoAcidSequences HeavychainA Rahlvgsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:81 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpeakfnw yvdgvevhnaktkpreegynstvvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:82 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgri SEQID tgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:83 yydfwwgyppgeeyfqdwgqgtlvivssdkthtgvhltqsgpevrkpgts vkvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfka kvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwa vdvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqt yicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpk dtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyns tyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgrqprepqvyt lppcerdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsd gsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrsplliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:84 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein11NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:85 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggagcctgaagcccgatgacaccgccgtatactactgca ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaatttgggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcac acctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagt gcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaagaccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcaggtgtccaagetgacagtggacaagtcccggt ggcagcagagcaacatgttcagctgaccgtgatacacgaggccctacacaaccact acacccagaagtccctgagcctgagccccggcaag LightchainA tacatccacgtgacccagagccecagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactggt NO:86 atcagcacaagcctggcagagcccccaagagctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:87 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtagactacgcggaatctgttaaagagcggtttacaatacaagagacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca ggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggt gtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcag cgtgccaggacagggactgcagtggatgggaggatcagccacgagggcgacaag aaagtgatcgtagaacggttcaaggccaaagtgaccatcgactgggacagaagcacc aacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtactact gcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggc gccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccagg gcacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagggcccatc ggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctggg ctgcctggtcaaggactacttccccgaaccggtgacgatgtcgtggaactcaggcgcc ctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccct cagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaac gtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtg acaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcag tcttcctcttccccccaaaacccaaggacaccacatgatacccggacccctgaggtca catgcatggtggtagacgtgagccacgaagaccctgaggtcaagttcaactggtatgtt gacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaaca gcacgtaccgtgtggtcagectcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagcccegagaaccacaggtgtacaccctgcccccatgcc gggatgaactgaccaagaatcaagtcagcctgtggtgcctgataaaaggcttctatccc agcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaaga ccacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtag acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctct gcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgaga SEQID gcgccagcatcagctgcaagagcagccactccctgatccacggcgaccggaa NO:88 caactacctggcttggtacgtgcagaagcccggcagatccccccagctgctga tctacctggccagcagcagagccagcgcgtgcccgatagattttctggcagc ggcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgaggac gtgggcacctactactgtatgcagggcagagagagcccctggacctttggcca gggcaccaaggtggacatcaaggacaaaacccataccgcatccgaactgact caggaccctgccgtctctgtggcactgaagcagactgtgactattacttgccga ggcgactcactgcggagccactacgcttcctggtatcagaagaaacccggcca ggcacctgtgctgctgttctacggaaagaacaataggccatctggcatccccga ccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccggcgc ccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacc catacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgag cagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccc cgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaa cagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcct gagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgta cgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttca accggggcgagtgt BindingProtein12AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:89 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:90 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgri SEQID tgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:91 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqmqlqesgpglvkpse tlsltcsvsgasisdsywswirrspgkglewigyvhksgdtnyspslksrvnl sldtsknqvslslvaataadsgkyycartlhgrriygivafnewftyfymdvw gngtqvtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtv swnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntk vdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcv vvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqd wlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltknqv slwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdks rwqqgnvfscsvmhealhnhytqkslslspg LightchainB sdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtaseltqdp NO:92 avsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgsas gnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthrttvaapsvfifp psdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysls stltlskadyekhkvyacevthqglsspytksfnrgec BindingProtein12NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:93 gcccctggcagaggactggaatgggttgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtaaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcac acctttccaactatgctgcagtccagcggcctgtacagcctaagcagcgtcgtgacagt gcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaaaaccctgaagtaaaattcaattagtacgtggacggcgtgaaaat gcacaacgccaagaccaagccaagagaagaacaatacaacagcacctaccgggta gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacgactcattatcaggtatccaagagacaatggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccggcaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctacagggcgtgggcagcgacctgcactggt NO:94 atcagcacaagectggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtgaagtcaagagaggggatgtgaagcccaatggatactccac SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:95 cctccaggtaaggggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggatacaatctcaagggacaatacca agaataccctgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca gatgcagctgcaggagagcggccctggactcgtgaagcccagcgagaccctgagcc tgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcagga ggagccctggcaagggcctggagtggatcggctacgtgcacaagageggegacacc aactacagcccctccctgaagtccagggtgaacctgtccctggacaccagcaagaacc aggtgagcctgtccctggtggctgccacagctgctgacagcggcaagtactactgtgc caggaccctacacggcaggaggatctacggcatcgtagccttcaacgagtagttcacc tacttctacatgaacatgtggggcaacggcacccaggtgaccgtgagctccgataaga cccacaccgcttccaccaagggcccatcggtcttccccctggcaccctcctccaagag cacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaacc ggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggc tgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagca gcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggt ggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccaccgtgccca gcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaaggaca ccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacga agaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgccaaga caaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctcacc gtcctgcaccaggactggctgaatagcaaggagtacaagtgcaagataccaacaaa gccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccgaga accacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagc aatgggcagccggagaacaactacaagaccacgcctcccgtgctggactccgacgg ctccttcttcctctactcaaaactcaccatggacaagagcaggtagcagcaggggaac gtcttctcatactccatgatgcatgaggctctgcacaaccactacacacagaagagcct ctccctgtctccgggt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgag SEQID aagagcctgggaagcagggctgtgcagtggtaccaacacagggccggacag NO:96 gctcccagcctgatcatctacaacaaccaggacaggcccagcggcatccctga gaggttcagcggaagccccgacagccccttcggaaccacagccaccctgacc atcacaagcgtggaagccggcgacgaggccgactactactgccacatctggg acagcagggtgcccaccaagtgggtgtttggcggcggcaccaccctgaccgt gctggacaaaacccataccgcatccgaactgactcaggaccctgccgtctctgt ggcactgaagcagactgtgactattacttgccgaggcgactcactgcggagcc actacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgttcta cggaaagaacaataggccatctggcatccccgaccgatttctggcagtgcatc agggaaccgagccagtctgaccattaccggcgcccaggctgaggacgaagc cgattactattgcagctcccgggataagagcggctccagactgagcgtgacgg aggaggaactaaactgaccgtcctcgataagacccatacccgtacggtggccg ctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcaca gcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcag tggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactga gcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccacc agggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein13AminoAcidSequences HeavychainA qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwishe SEQID gdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydd NO:97 dgalnwavdvdylsnlefwgqgtavtvssastkgpsvfplapsskstsggtaalgcl vkdvfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvn hkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevt cvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltylhqdwl ngkeykckvsnkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkg fypsdiavewesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsv mhealhnhytqkslslspg LightchainA dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtva NO:98 apsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqd skdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:99 yydfwwgyppgeeyfqdwgqgtlvivssdkthtqmqlqesgpglvkpse tlsltcsvsgasisdsywswirrspgkglewigyvhksgdtnyspslksrvnl sldtskngyslslvaataadsgkyycartlhgrriygivafnewftyfymdv wgngtqvtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepv tvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsn tkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdttmisrtpevt evvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlh qdwlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltkn qvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltv dksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB sdisvapgetariscgekslgsravgwyqhragqapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtaseltqd NO:100 pavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgs asgnrasltitgaqacdeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfif ppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstys lsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein13NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgagtgcg NO:101 cagcgtgccaggacagggactacagtggatgaactagatcaaccacgaggacgac aagaaagtgatcatggaacggttcaaggccaaagtgaccatcgactaggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggc cagggcacagccgtgaccgtgtcatctgcttcgaccaagggccccagcgtgttccctc tggcccctagcagcaagagcacataggcggaacagccgccagggctgcctcgtga aggactactacccgagcccgtgaccgtgtcaggaattaggcgccctgaccagcgg cgtgcacacctttccaactatgctgcagtccagcggcctgtacagcctgagcagcgtc gtgacagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccaca agcccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagac ccacacctgtcccccagtcctgcccccgaactgctgggaggcccttccgtgttcctgtt ccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcg tggtggtggatgtatcccacgaggaccagaaatgaagttcaattggtacgtagacgg cgtggaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacct accgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagt acaagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagca aggccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcaggga cgagagaccaagaaccaggtgtccctgagagtgccgtgaaaggatctacccacc gatatcgccgtagaatgggagagcaacagccagcccgagaacaactacaagaccac cccccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggaca agtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgc acaaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gacacgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:102 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtaggcacctactactgtatgcagg gcagagagaacccaggacattggccagagcaccaaagtggacatcaaacgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtg gaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagca ggacagcaaggactccacctacagcctgagcagcaccagacactgagcaaggccg actacgagaagcacaaggtgtacgcctacgaagtgacccaccaaggcctgtctagcc ccgtgaccaagagatcaaccgaggcgagtat HeavychainB gaggttagactggtggagtcaggaggggggcagtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:103 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtggggctatccccctggcgaggaata ttttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccca gatgcagctgcaggagagcggccctggactcgtgaagcccagcgagaccctgagcc tgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcagg aggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgaca ccaactacagcccctccctgaagtccagagtgaacctatccaggacaccagcaaga accaggtgagcctgtccaggtggctgccacagctgctgacagcggcaagtactactg tgccaggaccctgcacggcaggaggatctacggcatcgtggccttcaacgagtggttc acctacttctacatggacgtgtggggcaacggcacccaggtgaccgtgagctccgata agacccacaccgcttccaccaagggcccatcggtcttccccctggcaccctcctccaa gagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccga accggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttccc ggctgtcctacaatcctcaggactctactccctcagcagcgtggtgaccgtgccacca gcagcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacacca aggtggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccaccgtg cccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaag gacaccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagcc acgaagaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgc caagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcc tcaccgtcctgcaccaggactggctgaatggcaaggagtacaaatgcaaggtctccaa caaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagcccc gagaaccacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaag tcagcctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtggga gagcaatgggcagccggagaacaactacaagaccacgcctcccgtgctggactccg acggctccttcttcctctactcaaaactcaccgtggacaagagcaggtggcagcaggg gaacgtcttctcatgctccgtgatacatgaggctctacacaaccactacacgcagaaga gcctctccctgtctccgggt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgag SEQID aagagcctgggaagcagggctgtgcagtggtaccaacacagggccggacag NO:104 gctcccagcctgatcatctacaacaaccaggacaggcccagcggcatccctg agaggttcagcggaagccccgacagccccttcggaaccacagccaccctga ccatcacaagcgtggaagccggegacgaggccgactactactgccacatctg ggacagcagggtgcccaccaagtgggtgtttggcggcggcaccaccctgac cgtgctggacaaaacccataccgcatccgaactgactcaggaccctgccgtct ctgtggcactgaagcagactgtgactattacttgccgaggcgactcactgcgga gccactacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgt tctacggaaagaacaataggccatctggcatccccgaccgcttttctggcagtg catcagggaaccgagccagtctgaccattaccggcgcccaggctgaggacg aagccgattactattgcagctcccgggataagagcggctccagactgagcgtg ttcggaggaggaactaaactgaccgtcctcgataagacccatacccgtacggt ggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccg gcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaa gtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaag cgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccct gacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagt gacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt BindingProtein14AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:105 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedg SEQID vpsrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsd NO:106 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmg SEQID wishegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgsk NO:107 hrlrdyalydddgalnwavdvdylsnlefwgqgtavtvssdkthtevrlves ggglvkpggslrlscsasgfdfdnawmtwvalppgkgtewvgritgpgeg wsvdyaesvkgrftisrdnktntlylemnnvrtedtgyyfcartgkyydfw wgyppgeeyfqdwgqgtlvivssdkthtastkgpsvfplapsskstsggtaa lgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgt qtyicnvnhkpsnkvdkkvepkscdkthtcppcpapellggpsvflfppk pkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeq ynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprep qvytlppcrdeltknqvslwclvkgfypsdiavewesngqpennykttppv ldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB aseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi SEQID pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtdfv NO:108 ltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqliiylassrasg vpdrfsgsgsdkdftlkisrvetedvatyycmqgrespwtfgqtkvdikdkthtrt vaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvte qdskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein14NucleotideSequences HeavychainA aaagcccacctaatgcagtctagcaccgccataaaaaaaccagacgcctctatgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggca NO:109 ggcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccg tgaacttcgacggaggcttccggaatagaatgaccctaacccaggacgtgtaccgcg agatcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactg cgccagagacagaagctacggcgacagcaactgggctctagatgcttggggccagg gcacaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggc ccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaagg actactttcccgagcccgtgaccgtgtcctggaattaggcgccctgaccagcggcgtg cacacctttccagagtgctgcagtccagcggcctgtacagcctgagcagcgtcgtga cagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagc ccagcaacaccaaggtggacaagaaggtggaacccaagagagcgacaagaccca cacctgtcccccttgtcctgcccccgaactgctgggaggcccttccatgttcctgttccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggt ggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtg gaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcacctacc gggtggtgtccgtgagaccgtgagcaccaggactggctgaacggcaaagagtaca agtgcaaggtgtccaacaaggccagcctgcccccatcgagaaaaccatcagcaagg ccaagggccagccccgcgaaccccaggtgtgcacactgcccccaaacagggacga gctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgat atcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccc cccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaag tcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcac aaccactacacccagaagtccctgagcctgagccccggcaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactggt NO:110 atcagcacaagcctggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtc aggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtg gccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccgg cacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagt gcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcg tgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctga cactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtga cccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtg t HeavychainB caggtgcacctgacacagagcggacccgaagtgcggaagcctagcacctagtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:111 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacaccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggc cagggcacagccgtgaccgtgtcatctgacaaaacccataccgaggttagactggtg gagtcaggaggggggcagtgaagcccggtgggtctctccgcctgagctgttctgcct ccggctttgatttcgataacgcctggatgacctgggtcaggcagcctccaggtaaggg actggagtgggtgggaagaatcacaggtccaggcgagggaggtccgtggactacg cggaatctgttaaagggcggtttacaatctcaagggacaataccaagaataccttgtattt ggagatgaacaacgtgagaactgaagacaccggatattacttctgtgccagaacaggc aaatactacgacttctggtggggctatccccctggcgaggaatattttcaagactggggt cagggaacccttgttatcgtgtcctccgataagacccacaccgcttccaccaagggcc catcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccct gggctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcagg cgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctact ccctcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctg caacgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatc ttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggacc gtcagtcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctg aggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaact ggtatgttgacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcag tacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctga atggcaaggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgaga aaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgccc ccatgccgggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggct tctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaac tacaagaccacgcctcccatgaggactccgacggaccttcttcactactcaaaactc accgtagacaagagcaggtggcagcaggagaacgtatacatgctccgtgatacat gaggctctgcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgt SEQID gactattacttgccgaggcgactcactgcggagccactacgcttcctggtatca NO:112 gaagaaacccggccaggcacctgtgctgctgttctacggaaagaacaatagg ccatctggcatccccgaccgcttttctggcagtgcatcagggaaccgagccagt ctgaccattaccggcgcccaggctgaggacgaagccgattactattgcagctc ccgggataagagcggctccagactgagcgtgttcggaggaggaactaaactg accgtcctcgacaaaacccataccgacttcgtgctgacccagagccctcacag cctgagcgtgacacctggcgagagcgccagcatcagctgcaagagcagcca ctccctgatccacggcgaccggaacaactacctggcttggtacgtgcagaagc ccggcagatccccccagctgctgatctacctggccagcagcagagccagcgg cgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaaga tcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcag agagagcccctsgacctttggccagggcaccaaggtggacatcaaggataag acccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgac gagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctac ccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacag cctgagcagcaccctgacactgagcaaggccgactacgagaagcacaaggt gtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagc ttcaaccggggcgagtgt BindingProtein15AminoAcidSequences HeavychainA qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwishe SEQID gdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydd NO:113 dgalnwavdvdylsnlefwgqgtavtvssastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvn hkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevt cvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwl ngkeykckvsnkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkg fypsdiavewesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsv mhealhnhytqkslslspg LightchainA dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtva NO:114 apsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqds kdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:115 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqmqlqesgpglvkpset lsltcsvsgasisdsywswirrspgkglewigyvhksgdtnyspslksrvnls ldtsknqvslslvaataadsgkyycartlhgrriygivafnewftyfymdvw gngtqvtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtv swnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntk vdkkvepkscdkthtcppcpapellggpsvfifppkpkdtlmisrtpevtcv vvdvshedpevkfnwyydgvevhnaktkpreeqynstyrvvsvltvlhqd wlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltknqv slwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdks rwqqgnvfscsvmhealhnhytqkslslspg LightchainB sdisvapgetariscgekslgsravqwyqhraaqapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtaseltgdp NO:116 avsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgsas gnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfifp psdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysls stltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein15NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:117 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggcc agggcacagccgtgaccgtgtcatctgcttcgaccaagggccccagcgtgttccctct ggcccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtga aggactactttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcgg cgtacacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtc gtgacagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccaca agcccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagac ccacacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgtt ccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgt ggtggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggc gtggaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcaccta ccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagta caagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaa ggccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggac gagctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccg atatcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccacc ccccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaa gtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgca caaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:118 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaagcgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtgg aaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcagg acagcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgact acgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccg tgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccagtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:119 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgaaaagggcggatacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacact gtgccagaacaggcaaatactacgacactagtccggctatccccctggcgaggaatat tttcaagactagggtcaaggaacccttgttatcgtgtcctccaacaaaacccatacccag atgcagctgcaggagageggccaggactcgtaaaacccagcgagaccctgagcct gacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcagga ggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgacacc aactacagcccctccctgaagtccagggtgaacctgtccctggacaccagcaagaacc aggtgagcctgtccctggtggctgccacagctgctgacagcagcaagtactactgtgc caggaccctacacggcaggaggatctacggcatcgtaaccttcaacgagtaattcacc tacttctacatggacgtgtggggcaacggcacccaggtgaccgtgagctccgataaga cccacaccgcttccaccaagggcccatcggtcaccccctggcaccctcctccaagag cacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaacc ggtgacggtgtcgtggaactcaagcgccctgaccagcggcatgcacaccttcccggc tgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagca gcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggt ggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccaccgtgccca gcacctgaactcctggggggaccgtcagtcttcctcttcccccccaaaaccaaggaca ccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacga agaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgccaaga caaagccacgggaggagcagtacaacagcacataccatgtagtcagcgtcctcacc gtcctgcaccaggactggctgaatagcaaggagtacaagtgcaagataccaacaaa gccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccgaga accacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagc aatgggcagceggagaacaactacaagaccacgcctcccgtgctggactccgacgg ctccttcttcctctactcaaaactcaccgtagacaaaagcaggtggcagcaggagaac gtcttctcatgctccgtaatacatgaagctctacacaaccactacacgcagaagagcct ctccctgtctccaggt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgag SEQID aagagcctgggaagcagggctgtgcagtggtaccaacacagggccggacag NO:120 gctcccagcctgatcatctacaacaaccaggacaggcccagcggcatccctga gaggttcagcggaagccccgacagccccttcggaaccacagccaccctgacc atcacaagcgtggaagccggcgacgaggccgactactactgccacatctggg acagcagggtgcccaccaagtgggtgtttggcggcggcaccaccctgaccgt gctggacaaaacccataccgcatccgaactgactcaggaccctgccgtctctgt ggcactgaagcagactgtgactattacttgccgaggcgactcactgcggagcc actacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgttcta cggaaagaacaataggccatctggcatccccgaccgcttactggcagtgcatc agggaaccgagccagtctgaccattaccggcgcccaggctgaggacgaagc cgattactattgcagctcccgggataagagcggctccagactgagcgtgttcgg aggaggaactaaactgaccgtcctcgataagacccatacccgtacggtggccg ctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcaca gcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcag tggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactga gcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccacc agggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein16AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:121 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:122 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:123 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqmqlqesgpglvkpset lsltcsvsgasisdsywswirrspgkglewigyvhksgdtnyspslksrvnls ldtsknqvslslvaataadsgkyycartlhgrriygivafnewftyfymdvw gngtqvtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtv swnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntk vdkkvepkscdkthtcppcpapellggpsvfifppkpkdtlmisrtpevtcv vvdvshedpevkfnwyydgvevhnaktkpreeqynstyrvvsvltvlhqd wlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltknqv slwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdks rwqqgnvfscsvmhealhnhytqkslslspg LightchainB sdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtaseltqdp NO:124 avsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgsas gnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfifp psdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysls stltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein16NucleotideSequences HeavychainA agaacccacctggtacagtctggcaccgccatgaagaaaccaggcgcctctgtacgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:125 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccggaatagaatgaccctaacccgagacgtgtaccgcgag atcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgaactctagatacttgggaccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcac acctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagt gcccagcagctctctgggcacccagacctacatagcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagagcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgaccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacaccaagaccaagccaagagaggaacagtacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactacccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccgacaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctacagggcgtgggcagcgacctgcactggt NO:126 atcagcacaagcctggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctaccgc SEQID ctaagctgactgcctccggattgatttcaataacgcctgaataacctgaatcaggcag NO:127 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcoogggacaatacca agaataccttgtataggagatgaacaacgtgagaactgaagacaccggatattacact gtgccagaacaggcaaatactacgacactggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccag atgcagctgcaggagagcggccaggactcgtgaaacccagcgagaccctgagcct gacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcagga ggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgacacc aactacagcccctccctgaagtccagggtgaacctgtccaggacaccagcaagaacc aggtgagcctgtccctggtggctgccacagctgctgacagcggcaagtactactgtgc caggaccctacacggcaggaggatctacggcatcgtaaccttcaacgagtaattcacc tacttctacatgaacatgtggggcaacggcacccaggtgaccgtgagctccgataaga cccacaccgcttccaccaagggcccatcggtcttccccctggcaccctcctccaagag cacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaacc ggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggc tgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagca gcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggt ggacaagaaaattaagcccaaatcagtgacaaaactcacacatgcccaccgtaccca gcacctgaactcctggaaggaccatcagtcttcctcttccccccaaaacccaaggaca ccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacga agaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgccaaga caaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctcacc gtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaa gccctcccagcccccatcgagaaaaccatctccaaaaccaaagggcagccccgaga accacaggtatacaccctgcccccataccaggatgaactaaccaagaatcaaatcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagc aatgggcagccggagaacaactacaagaccacgcctcccgtgctggactccgacgg ctccttcttcctctactcaaaactcaccgtggacaagagcaggtggcagcaggggaac gtcttctcatgctccdgatgcatgaggctctgcacaaccactacacgcagaagagcct ctccctgtctccgggt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgag SEQID aagagcctgggaagcagggctgtgcagtggtaccaacacagggccggacag NO:128 gctcccagcctgatcatctacaacaaccaggacaggcccagcggcatccctga gaggttcagcggaagccccgacagcccatcggaaccacagccaccctgacc atcacaagcgtggaagccggcgacgaggccgactactactgccacatctggg acagcagggtgcccaccaagtgggtgtttggcggcggcaccaccctgaccgt gctggacaaaacccataccgcatccgaactgactcaggaccctgccgtctctgt ggcactgaagcagactgtgactattacttgccgaggcgactcactgcggagcc actacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgttcta cggaaagaacaataggccatctggcatccccgaccgatttaggcagtgcatc agggaaccgagccagtctgaccattaccggcgcccaggctgaggacgaagc cgattactattgcagctcccgggataagagcggctccagactgagcgtgttcgg aggaggaactaaactgaccgtcctcgataagacccatacccgtacggtggccg ctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcaca gcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcag tggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactga gcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccacc agggcctgtctagccccgtgacaagagcttcaaccggggcgagtgt BindingProtein17AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:129 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:130 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmg SEQID wishegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgsk NO:131 hrlrdyalydddgalnwavdvdylsnlefwgqgtavtvssdkthtqmqlqe sgpglvkpsetlsltcsvsgasisdsywswirrspgkglewigyvhksgdtn yspslksrvnlsldtsknqvslslvaataadsgkyycartlhgrriygivafne wftyfymdvwgngtqvtvssdkthtastkgpsvfplapsskstsggtaalgc lvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqty icnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkd tlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynst yrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppcrdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdg sfflyskltvdksrwgqgnvfscsvmhealhnhytqkslslspg LightchainB sdisvapgetariscgekslgsravqwyqhragapsliiynnqdrpsgiperfsgsp SEQID dspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtdfvltqsp NO:132 hslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassrasgvpdrf sgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltskadyekhkvyacevthqglsspvtksfhrgec BindingProtein17NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:133 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggggcagaagcccgatgacaccgccgtgtactactgcg ccagagacagaagaacggcgacagcagagagactagatgatgggaccagggc acaaccgtggtggtgtagccgcactacaaagggccccagcgtgttccctaggcccc tagcagcaagagcacataggcggaacagccgccagggagcacgtgaaggacta ctttcccgagcccgtgaccgtgtcaggaattaggcgccctgaccagcggcgtgcac accctttccagagtgagcagtccagcggcagtacagcagagcagcgtcgtgacagt gcccagcagactagggcacccagacctacatagcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagagcgacaagacccacaca gtcccccttgtcagcccccgaactgagggaggcccttccgtgttcagttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccagaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaggaacagtacaacagcacaaccgggtg gtatccgtgagaccgtgagcaccaggaaggagaacgacaaagagtacaagtgc aaggtgtccaacaaggccagcctacccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagaga ccaagaaccaggtgtccagagagtgccgtgaaaggatctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccctgagcctgagccccggcaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctacagggcgtgggeagcgacctgcactggt NO:134 atcagcacaagcctggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:135 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgagacagaagc accaacaccgcctacctacagctaagcggcctgacctaggcgataccgccgtgtact actgcaccaaaagcagcaagcaccgactaagaaactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggcc agggcacagccgtgaccgtgtcatctgacaaaacccatacccagatgcagctgcagg agagcggccctggactcgtgaagcccagcgagaccctgagcctgacatgcagcgtg agcggcgccagcatcagcgacagetactggagctggatcaggaggagccctggcaa gggcctgaagtagatcggctacgtgcacaagagcaacgacaccaactacagcccct ccctgaagtccagggtgaacctgtccaggacaccagcaagaaccaggtgagcctgt ccctggtggctgccacagctgctgacagcggcaagtactactgtgccaggaccctgca cggcaggaggatctacggcatcgtggccttcaacgagtggttcacctacttctacatgg acgtgtggggcaacgcacccaggtgaccgtgagctccgataagacccacaccgctt ccaccaagggcccatcggtcttccccctggcaccctcctccaagagcacctggggg cacagcagccctaggctgcctgatcaagaactacttccccaaaccaatgacggtgtc gtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcc tcagaactctactccctcagcagcatggtgaccgtgccaccagcagataggcaccc agacctacatagcaacgtgaatcacaagcccagcaacaccaaggtggacaagaaag ttgagcccaaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactc ctggggggaccgtcagtcttcctcttccccccaaaacccaaggacaccctcatgatctc ccggaacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggt caagttcaactagtatgttgacggcgtaaaggtgcataataccaaaacaaagccgcgg gaggagcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccag gactggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcccagcc cccatcgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgta caccctgcccccatgccgggatgagctgaccaagaatcaagtcagcctgtggtgcctg gtaaaagacttctatcccaacgacatcaccatggagtaagagagcaatgggcagccg gagaacaactacaagaccacgcctcccatgaggactccaacggaccacttcctcta ctcaaaactcaccgtggacaagagcaggtggcagcaggggaacgtcttctcatgctcc gtgatgcatgaggactgcacaaccactacacgcagaagagcctctccctgtctccgg gt LightchainB tccgacatcagcgtggcccccggagagacagccaggatctcctgcggcgag SEQID aagagcctgggaagcagggctgtgcagtggtaccaacacagggccggacag NO:136 gctcccagcctgatcatctacaacaaccaggacaggcccagcggcatccctga gaggttcagcggaagccccgacagcccatcggaaccacagccaccctgacc atcacaagcgtggaagccggcgacgaggccgactactactgccacatctggg acagcagggtgcccaccaagtgggtgtttggcggcggcaccaccctgaccgt gctggacaaaacccataccgacttcgtgctgacccagagccctcacagcctga gcgtgacacctggcgagagcgccagcatcagctgcaagagcagccactccct gatccacggcgaccggaacaactacctggcttggtacgtgcagaagcccggc agatccccccagctgagatctacctggccagcagcagagccagcggcgtgc ccgatagattttctggcagcggcagcgacaaggacttcaccctgaagatcagc cgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagag agcccctggacctttggccagggcaccaaggtggacatcaaggataagaccc atacccgtacggtggccgctcccagcgtgttcatatcccacctagcgacgagc agctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaac agccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtac gcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaa ccggggcgagtgt BindingProtein18AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:137 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:138 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB qmqlqesgpglvkpsetlsltcsvsgasisdsywswirrspgkglewigyvh SEQID ksgdtnyspslksrvnlsldtsknqvslslvaataadsgkyycartlhgrriygi NO:139 vafnewftyfymdvwgngtqvtvssdkthtevrlvesggglvkpggslrls csasgfdfdnawmtwvrqppgkglewvgritgpgegwsvdyaesvkgrf tisrdntkntlylemnnyrtedtgyyfcartgkyydfwsgyppgeeyfqdw gqgtlvivssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtv swnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntk vdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcv vvdvshedpevkfnwyvdgvevhnaktkpreegynstyrvvsvltvlhqd wlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltknqv slwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdks rwqqgnvfscsvmhealhnhytqkslslspg LightchainB aseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtsdis NO:140 vapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgspdsp fgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtrtvaapsvfif ppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstys lsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein18NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctatcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:141 gcccaggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccaccctaggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctagaattctgacgccctgaccagcggcgtgcac acctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagt gcccagcagctctctgggcacccaaacctacatagcaacgtgaaccacaagcccag caacaccaaggtggacaagaaggtggaacccaagagagcgacaagacccacacct gtcccccttgtcctgcccccaaactactaagagacccttccgtgttcctattccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaggaacagtacaacagcacctaccgggtg gtgtccgtgctgaccatgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctacccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaagtgtgcacactgcccccaagcagggacaagctga ccaagaaccaggtatccctgaactatgccgtaaaaggcactacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgacagctgctccgtgatgcacgaggccctgcacaaccact acacccagaagtccagagcctgagccccgacaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactggt NO:142 atcagcacaagcctggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB cagatgcagctgcaggagagcgaccctggactcgtgaagcccagcgagaccctgag SEQID cctgacatgcagcgtgagcagcgccagcatcagcgacagctactagagctggatcag NO:143 gaggagccctggcaagggcaggaatggatcggctacgtgcacaaaagcggcgac accaactacagcccctccctgaagtccaggatgaacctatccctggacaccagcaaga accaggtaagcctgtccctggtggctgccacagctgctgacagcgacaagtactactg tgccaggaccctgcacgacaggaggatctacggcatcgtggccttcaacgagtggttc acctacactacatggacgtgtgaggcaacggcacccaggtgaccgtgagctccgaca aaacccataccgaggttagactggtggagtcaggaggggggcttgtgaagcccggtg ggtctctccgcctgagctgttctgcctccggctttgatttcgataacgcctggatgacctg ggtcaggcagcctccaggtaagaaactggagtgaatggaaaaaatcacaagtccag gcgagggctggtccgtggactacgcggaatctgttaaagggcggtttacaatctcaag ggacaataccaagaataccttgtatttggagatgaacaacgtgagaactgaagacacc ggatattacttagtgccagaacaggcaaatactacgacttctggtccagctatccccct ggcgaggaatattttcaagactggggtcagagaacccttgttatcgtgtcctccaataag acccacaccgcttccaccaagggcccatcggtcttccccaggcaccctcctccaaga gcacctagggggcacageggccagggctgcaggtcaaggactacttccccgaac cggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccgg ctgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagc agcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaag gtggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccaccgtgcc cagcacctgaactcctggaaggaccgtcagtatcctatccccccaaaacccaagga caccctcatgatctcccgaacccctgaggtcacatgcatggtggtgaacatgaaccac gaagaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgccaa gacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctca ccgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaaca aagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccga gaaccacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtc aacctgtagtgcctggtaaaaggatctatcccagcgacatcgccgtggagtgggaga acaataggcagccggagaacaactacaagaccacgcacccgtactagactccgac ggctcatatcactactcaaaactcaccgtgaacaagagcaggtggcagcagggga acgtatctcatgaccgtgatgcatgaggctctgcacaaccactacacgcagaagagc ctaccctgtctccgggt LightchainB gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgtg SEQID actattacttgccgaggcgactcactgcggagccactacgcacctggtatcaga NO:144 agaaacccggccaggcacctgtgctgctgttaacggaaagaacaataggcca tctggcatccccgaccgcttttctggcagtgcatcagggaaccgagccagtctg accattaccggcgcccaggctgaggacgaagccgattactattgcagctcccg ggataagagcggctccagactgagcgtgttcggaggaggaactaaactgacc gtcctcgacaaaacccatacctccgacatcagcgtggcccccggagagacag ccaggatacctgcggcgagaagagcagggaagcagggctgtgcagtggta ccaacacagggccggacaggctcccagcctgatcatctacaacaaccaggac aggcccagcggcatccctgagaggttcagcggaagccccgacagccccttcg gaaccacagccaccctgaccatcacaagcgtggaagccggcgacgaggccg actactactgccacatctgggacagcagggtgcccaccaagtgggtgtttggc ggcggcaccaccctgaccgtgctggataagacccatacccgtacggtggccg ctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcaca gcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcag tggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactga gcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccacc agggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein19AminoAcidSequences HeavychainA evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgpg SEQID egwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyydfwsgy NO:145 ppgeeyfqdwgqgtlvivssastkgpsvfplapsskstsggtaalgclvkdyfpepv tvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvd kkvepkscdkthtcppcpapellggpsvflfppkdtlmisrtpevtcvvvdvshe dpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckv snkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiave wesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnh ytqkslslspg LightchainA aseltqdpavsvalkqtvtitcrgdslrshyaswygkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvlsqpkaaps NO:146 vtlfppsseelqankatlvclisdfypgavtvawkadsspvkagvetttpskqsnnky aassylsltpeqwkshrsyscqvthegstvektvaptecs HeavychainB qmqlqesgpglvkpsetlsltcsvsgasisdsywswirrspgkglewigyvh SEQID ksgdtnyspslksrvnlsldtsknqvslslvaataadsgkyycartlhgrriygi NO:147 vafnewftyfymdvwgngtqvtvssdkthtQvhltqsgpevrkpgtsvkv sckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkakvti dwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwavdv dylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgclvk dyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicn vnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlm isrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrv vsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsf flyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmggrespwtfgqgtkvdikdkth NO:148 tsdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgs pdspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein19NucleotideSequences HeavychainA gaggttagactggtggagtcaggaggggggcagtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:149 cctccagataagggactagagtgggtgggaagaatcacagatccagacgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttaggtccggctatccccaggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgcgtcgaccaagggccc cagcgtgttccactggcccctagcagcaagageacataggcggaacagccgccct gggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctagaattaggcg ccctgaccagcggcgtgcacacctttccagctgtgctgcagtccagcggcctgtacag cctgagcagcgtcgtgacagtgcccagcagctctctgggcacccagacctacatctgc aacgtgaaccacaageccageaacaccaaggtggacaagaaggtggaacccaaga gctgcgacaagacccacacctgtcccccttgtcctgcccccgaactgagggaggccc ttccgtgttcctgttccccccaaagcccaaggacaccctgatgatcaaccggaccccca aagtgacctgcgtggtggtagatgtgtcccacgaggaccctgaagtgaagttcaattgg tacgtggacggcgtggaagtgcacaacgccaagaccaagccaagagaggaacagta caacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaac ggcaaagagtacaagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaa accatcagcaaggccaagggccagccccgcgaaccccaggtgtgcacactgccccc aagcagggacgagagaccaagaaccaggtgtccctgagagtgccgtgaaaggctt ctacccctccgatatcgccgtagaatgggagagcaacagccagcccgagaacaacta caagaccaccccccctatgaggacagcgacgactcattatcaggtatccaagaga cagtggacaagtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacg aggcccggcacaaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgtg SEQID actattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga NO:150 agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggcca tctggcatccccgaccgcttttctggcagtgcatcagggaaccgagccagtctg accattaccggcgcccaggctgaggacgaagccgattactattgcagctcccg ggataagagcggctccagactgagcgtgttcggaggaggaactaaactgacc gtcctcagtcagcccaaggctgccccctcggtcactctgttcccgccctcgagt gaggagatcaagccaacaaggccacactggtgtgtctcataagtgacttctac ccgggagccgtgacagtggcaggaaggcagatagcagccccgtcaaggcg ggagtggagaccaccacaccctccaaacaaagcaacaacaagtacgcggcc agcagctacctgagcctgacgcctgagcagtggaagtcccacagaagctaca gctgccaggtcacgcatgaagggagcaccgtggagaagacagtggccccta cagaatgttca HeavychainB cagatgcagctgcaggaganggccctggactcgtgaagcccagcgagaccctgag SEQID cctgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcag NO:151 gaggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgac accaactacagcccctccctgaagtccagggtgaacctgtccctggacaccagcaaga accaggtgagcctgtccctggtggctgccacagctgctgacagcggcaagtactactg tgccaggaccctgcacggcaggaggatctacggcatcgtggccttcaacgagtggttc acctacttctacatggacatgtagggcaacggcacccaggtaaccgtgagctccgaca aaacccatacccaaatgcacctaacacagaacggacccgaagtgcggaagcctggc acctagtgaaggigtcctgcaaggcccctggcaacaccctgaaaacctacgacctgc actgggtgcgcagcgtgccaggacagggactgcagtggatgggctggatcagccac gagggcgacaagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgg gacagaagcaccaacaccgcctacctgcagctgagcggcctgacctctggcgatacc gccgtgtactactgcgccaagggcagcaagcaccggctgagagactacgccctgtac gacgatgacggcgccagaactgggccgtagatgtgaactacctgagcaacctggaa ttctgaggccaggacacaaccatgaccatgtcatctgataaaacccacaccgcttcca ccaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggcac agcggccctgggctgcaggtcaaggactacttccccgaaccggtgacggtgtcgtgg aactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcaacagtcctcag gactctactccctcagcgtggtgaccgtgccctccagcagcttgggcacccagac ctacatagcaacgtaaatcacaagcccagcaacaccaaagtgaacaagaaagttga gcccaaatatatgacaaaactcacacatgcccaccgtacccaacacctgaactcagg ggggaccgtcagtcttcctcttccccccaaaacccaaggacaccctcatgatctcccgg acccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaag ttcaactggtatgttgacggcgtggaggtgcataatgccaagacaaagccgcgggagg agcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactg gctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcccagcccccat cgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacaccc tgcccccatgccgggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaa aggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagccggaga acaactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctactcaa aactcaccgtggacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgat gcatgaggctctgcacaaccactacacgcagaagagcctaccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgaga SEQID gcgccagcatcagctgcaagagcagccactccctgatccacggcgaccggaa NO:152 caactacctggcttggtacgtgcagaagcccggcagatccccccagctgctga tctacctggccagcagcagagccagcggcgtgcccgatagattttctggcagc ggcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgaggac gtgggcacctactactgtatgcagggcagagagagccectggacctttggcca gggcaccaaggtggacatcaaggacaaaacccatacctccgacatcagcgtg gcccccggagagacagccaggatctcctgcggcgagaagagcctgggaag cagggctgtgcagtggtaccaacacagggccggacaggctcccagcctgatc atctacaacaaccaggacaggcccagcggcatccagagaggttcagcggaa gccccgacagccccttcggaaccacagccaccctgaccatcacaagcgtgga agccggcgacgaggccgactactactgccacatctgggacagcagggtgcc caccaagtgggtgtttggcggcggcaccaccctgaccgtgctggataagaccc atacccgtacggtggccgctcccagcgtgttcatatcccacctagcgacgagc agctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaac agccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctg agcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtac gcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaa ccggggcgagtgt BindingProtein20AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqy SEQID gavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswalda NO:153 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslsp g LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikrtvaapsvfifppsde NO:154 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvtksfnrgec HeavychainB qmqlqesgpglvkpsetlsltcsvsgasisdsywswirrspgkglewigyvh SEQID ksgdtnyspslksrvnlsldtsknqvslslvaataadsgkyycartlhgrriygi NO:155 vafnewftyfymdvwgngtqvtvssdkthtQvhltqsgpevrkpgtsvkv sckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkakvti dwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwavdv dylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgclvk dyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicn vnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlm isrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrv vsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsf flyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:156 tsdisvapgetariscgekslgsravqwyqhragqapsliiynnqdrpsgiperfsgs pdspfgttatltitsveagdeadyychiwdsrvptkwvfgggttltvldkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein20NucleotideSequences HeavychainA agagcccacctggtgcagtaggcaccgccatgaagaaaccaggcgcctagtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgactggttccggca NO:157 ggcccctggcagaggactggaatgagtgggatagatcaagccccagtatggcacca tgaacttcagcgaaggcaccaggatagagtgaccctgacccgggacgtgtaccacg agatcgcctacatggacatccggggectgaagcccgatgacaccgccgtatactacta cgccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagg gcacaaccgtagtggtgtctgccgcctctacaaagggccccagcgtgttccactgac ccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaagg actactttcccgagcccgtgaccgtgtcctggaattctagcgccctgaccagcggcgtg cacacctttccagctgtgctgcagtccagcgacctgtacagcctgagcagcatcatga cagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagcc cagcaacaccaaggtagacaagaaggtggaacccaagagctgcgacaagacccac acctgtcccccttgtcctgcccccgaactgagggaggcccaccgtattcctgttcccc ccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtg gtggatgtgtcccacgaagaccctgaagtgaagacaattggtacgtggacggcgtgg aagtgcacaacgccaagaccaagccaagagaggaacagtacaacaacacctaccgg gtgatgtccatgctgaccatgctgcaccaagactggctgaacggcaaagagtacaagt gcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggcca agggccagccccgcgaaccccaggtatgcacactgcccccaagcagggacgagct gaccaagaaccaggtgtccctgagctgtgccgtaaaaggcttctacccctccgatatcg ccgtggaatgggagagcaacggccaacccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccg gtggcagcagggcaacgtgacagctgctccgtgatgcacgaggccctgcacaacca ctacacccagaagtccctgagcctgagccccggcaag LightchainA tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactggt NO:158 atcagcacaagcctggcagagcccccaagctgctgatccaccacacaagcag cgtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagct tcaacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtca ggtgctgcagttcttcggcagaggcagcagactgcacatcaagcgtacggtgg ccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggc acagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtg cagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgt gaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgac actgagcaaggccgactacgagaageacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB cagatgcagctgcaggagagcggccctggactcgtgaagcccagcgagaccctgag SEQID cctgacatgcagcgtgagcggcgccagcatcagcgacagctactggagctggatcag NO:159 gaggagccctggcaagggcctggagtggatcggctacgtgcacaagagcggcgac accaactacagcccctccctgaagtccagggtgaacctgtccctagacaccaacaaga accaagtgagcctatccctggtaactaccacagctgctgacaacggcaagtactactg tgccagaaccctgcacgacaaaaggatctacggcatcgtggccttcaacaagtagttc acctacttctacatggacgtgtggggcaacggcacccaggtgaccgtgagctccgaca aaacccatacccaggtgcacctgacacagagcggacccgaagtgcggaagcctggc acctctgtgaaggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgc actgggtgcgcagcgtgccagaacagggactgcagtggatgggctggatcagccac gagggcgacaagaaagtgatcgtggaacaattcaaggccaaagtgaccatcgactg ggacaaaaacaccaacaccgcctacctacaactaagcggcctgacctctggcgatac cgccgtatactactacgccaaggacaacaagcaccggctgagagactacaccctata cgacgatgacggcgccctgaactgggccgtggatgtggactacctgagcaacctgga attctggggccagggcacagccgtgaccgtgtcatctgataagacccacaccgcttcc accaagggcccatcggtcttccccctggcaccctcctccaagagcacctctgggggca cagcgaccctaggctgcctggtcaaggactacttccccgaaccgatgacggtgtcgtg gaactcaggcgccctgaccagcgacgtgcacaccttcccggctgtcctacagtcctca ggactctactccctcagcagcgtagtgaccgtgccctccaacaacttgggcacccaga cctacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaagaaagttga gcccaaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaactcctgg ggggaccgtcagtcttcctcttccccccaaaacccaaggacaccacatgatctcccgg acccctgaggtcacatacgtggtgatggacgtgagccacgaagaccagagatcaag ttcaactggtatgttgacggcgtggaggtgcataatgccaagacaaagccgcgggag gagcagtacaacagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggact ggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcccagccccca tcgagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacacc ctgcccccataccgggatgaactaaccaagaatcaagtcagcagtggtgcctgataa aaggcttctatcccagcaacatcgccgtagagtgggagagcaatgggcaaccggag aacaactacaagaccacgcctcccatgaggactccaacggctccttcttcctctactca aaactcaccgtggacaagagcaggtggcagcaggggaacgtatctcatgctccgtg atgcatgaggctctgcacaaccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgaga SEQID gcgccagcatcagctgcaagagcagccactccctgatccacggcgaccgga NO:160 acaactacctggcttggtacgtgcagaagcccggcagatccccccagctgctg atctacctggccagcagcagagccagcggcgtgcccgatagattttctggcag cggcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgagga cgtgggcacctactactgtatgcagggcagagagagcccaggaccatggcc agggcaccaaggtggacatcaaggacaaaacccatacctccgacatcagcgt ggcccccggagagacagccaggatctcctgcggcgagaagagcctgggaa gcagggctgtgcagtggtaccaacacagggccggacaggctcccagcctgat catctacaacaaccaggacaggcccagcggcatccctgagaggttcagcgga agccccgacagccccttcggaaccacagccaccctgaccatcacaagcgtgg aagccggcgacgaggccgactactactgccacatagggacagcagggtgc ccaccaagtgggtgtttggcggcggcaccaccagaccgtgctggataagacc catacccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgag cagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccc cgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaa cagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcct gagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgta cgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttca accggggcgagtgt BindingProtein21AminoAcidSequences HeavychainA qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwishe SEQID gdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydd NO:161 dgalnwavdvdylsnlefwgqgtavtvssastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvn hkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevt cvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwl ngkeykckvsnkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkg fypsdiavewesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsv mhealhnhytqkslslspg LightchainA dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtva NO:162 apsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqds kdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:163 yydfwsgyppgeeyfqdwgqgtlvivssdktht rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwik pqygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygd sswaldawgqgttvvvsadkthtastkgpsvfplapsskstsggtaalgclvk dyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicn vnhkpsntkvdkkvepkscdkthtcppcpapellggpsvfifppkpkdtlm isrtpevtcvvvdvshedpevkfnwyydgvevhnaktkpreeqynstyrv vsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsf flyskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtaseltqdpavs NO:164 valkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsgsasgnr asltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfifppsd eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekkhvyacevthqglsspvtksfnrgec BindingProtein21NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:165 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggcc agggcacagccgtgaccgtgtcatctgcttcgaccaagggccccagcgtgttccctct ggcccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtga aggactactttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcgg cgtacacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtc gtgacagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccaca agcccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagac ccacacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgtt ccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgt ggtggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggc gtggaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcaccta ccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagta caagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaa ggccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggac gagctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccg atatcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccacc ccccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaa gtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgca caaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:166 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaagcgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtgg aaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcagg acagcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgact acgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccg tgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgaactgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaagcag NO:167 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccataccaga gcccacctggtacaatctggcaccgccatgaagaaaccaggcgcctctgtgcgggtg tcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcaggc ccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtgaa cttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgagat cgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcgc cagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggca caaccgtggtggtgtctgccgataagacccacaccgcttccaccaagggcccatcggt cttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctg cctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgccctg accagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctcag cagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtg aatcacaagcccagcaacaccaaggtggacaagaaagagagcccaaatcttgtgaca aaactcacacatgcccaccgtgcccagcacctgaactcctaaggggaccgtcagtat cctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaagtcacat gcgtggtggtagacgtgagccacgaagaccctgaggtcaagttcaactggtatattga cggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaacagc acgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaagg agtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctc caaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgccggg atgaactaaccaagaatcaagtcagcctgtgatgcctaataaaaggcttctatcccagc aacatcgccgtagagtgggagagcaatggacaaccagagaacaactacaagaccac gcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtggacaa gagcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcac aaccactacacgcagaagagcctctccctgtctccgggt LightchainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:168 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatc tgcaggccgacgacattaccacctactattgtcaaatgctgcagttcttcggcagaagc agcagactgcacatcaaggacaaaacccataccgcatccgaactgactcaggaccct gccgtctctgtggcactgaagcagactgtgactattacttgccgaggcgactcactgcg gagccactacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgttct acggaaagaacaataggccatctggcatccccgaccgcttttctggcagtgcatcagg gaaccgagccagtctgaccattaccggcgcccaggctgaggacgaagccgattacta ttgcagctcccgaaataagagcggctccagactgagcgtgttcggaagagaaactaa actgaccgtcctcgataagacccatacccgtacggtggccgctcccagcgtgttcatctt cccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaac aacttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagc ggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcct gagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcct gcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggc gagtgt BindingProtein22AminoAcidSequences HeavychainA qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwishe SEQID gdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydd NO:169 dgalnwavdvdylsnlefwgqgtavtvssastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvn hkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevt cvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwl ngkeykckvsnkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkg fypsdiavewesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsv mhealhnhytqkslslspg LightchainA dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtva NO:170 apsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqds kdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwik SEQID pqygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygd NO:171 sswaldawgqgttvvvsadkthtevrlvesggglvkpggslrlscsasgfdfd nawmtwvrqppgkglewvgritgpgegwsvdyaesvkgrftisrdntknt lylemnnvrtedtgyyfcartgkyydfwsgyppgeeyfqdwgqgtlvivss dkthtastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgalts gvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepk scdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshed pevkfnwyvdgvevhnaktkpreeqynstytvvsvltvlhqdwlngkey kckvsnkalpapiektiskakgqprepqvytlppcrdeltknqvslwclvkg fypsdiavewesngqpennykttppvldsdgsf LightchainB aseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldktht NO:172 Yihvtqspsslsvsigdrvtincqtsqtsqgvsdhwyqhkpgrapkllihhtssvedg vpsrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrasrlhik dkthtrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgns qesvteqdskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein22NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaa SEQID ggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcg NO:173 cagcgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgac aagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagc accaacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtact actgcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgac ggcgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggcc agggcacagccgtgaccgtgtcatctgcttcgaccaagggccccagcgtgttccctct ggcccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtga aggactactttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcgg cgtacacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtc gtgacagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccaca agcccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagac ccacacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgtt ccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgt ggtggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggc gtggaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcaccta ccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagta caagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaa ggccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggac gagctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccg atatcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccacc ccccctgtgctggacagcgacggctcattcttcctggtgtccaagctgacagtggacaa gtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacgaggccctgca caaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:174 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagg gcagagagagcccctggacctttggccagggcaccaaggtggacatcaagcgtacg gtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtgg aaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcagg acagcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgact acgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccg tgaccaagagcttcaaccggggcgagtgt HeavychainB agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:175 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatagacatccagggcctaaaacccgatgacaccaccatgtactactgcg ccagagacagaagctacggcgacagcagctgaactctagatacttgggaccagggc acaaccgtgatggtgtctgccgacaaaacccataccgaggttagactggtggagtcag gaggggggcttgtgaagcccggtgggtactccgcctgagagactgcctccggcttt gatttcgataacgcctggatgacctgggtcaggcagcctccaggtaagggactggagt gggtgggaagaatcacaggtccaggcgagggctggtccgtggactacgcggaatct gttaaagggcggtttacaatctcaagggacaataccaagaataccttgtatttggagatg aacaacgtgagaactgaagacaccgaatattacttctgtgccagaacaggcaaatacta cgacttctggtccggctatccccctggcgaggaatattttcaagactggggtcagggaa cccttgttatcgtgtcctccgataagacccacaccgcttccaccaagggcccatcggtct tccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcc tggtcaaggactacttccccgaaccagtgacggtgtcgtggaactcaggcgccctgac cagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctcagca gcgtggtaaccgtaccctccagcagcttgggcacccagacctacatctgcaacgtgaa tcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtgacaaa actcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcct cttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtcacatgc gtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtatgttgacg gcgtggaggtgcataatgccaagacaaagccgcgggaggaacagtacaacagcac gtaccgtatggtcagcgtcctcaccgtcctgcaccaggactggctgaatgacaaggag tacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccatctcca aagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgccgggat gagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatcccagcga catcgccgtggagtgggagagcaatgggcagccggagaacaactacaagaccacgc ctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtggacaaga gcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaa ccactacacgcagaagagcctctccctgtctccgggt LightchainB gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgtg SEQID actattacttgccgaggcgactcactgcggagccactacgcttatggtatcaga NO:176 agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggcca tctggcatccccggccgctttctggcagtgcatcagggaaccgagccagtctg accattaccggcgcccaggctgaggacgaagccgattactattgcagctcccg ggataagagcggctccagactgagcgtgttcggaggaggaactaaactgacc gtcctcgacaaaacccatacctacatccacgtgacccagagccccagcagcct gtccgtgtccatcggcgacagagtgaccatcaactgccagacctctcagggcg tgggcagcgacctgcactggtatcagcacaagcctggcagagcccccaagct gctgatccaccacacaagcagcgtggaagatggcgtgcccagcagattttccg gcagcggcttccacaccagcttcaacctgaccatcagcgatctgcaggccgac gacattgccacctactattgtcaggtgctgcagttcttcggcagaggcagaga ctgcacatcaaggataagacccatacccgtacggtggccgctcccagcgtgtt catcttcccacctagcgacgagcagctgaagtccggcacagcctagtcgtgtg cctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggac aacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacag caaggactccacctacagcctgagcagcaccctgacactgagcaaggccgac tacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtcta gccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein23AminoAcidSequences HeavychainA evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgpg SEQID egwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyydfwsgy NO:177 ppgeeyfqdwgqgtlvivssastkgpsvfplapsskstsggtaalgclvkdyfpepv tvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsnkvd kkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshe dpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckv snkalpapiektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiave wesngqpennykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnh ytqkslslspg LightchainA Aseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi SEQID pdrfsgsasgnrasltitaaqaedeadyycssrdksgsrlsvfgggtkltvlsqpkaap NO:178 svtlfppsseelqankatlvclisdfypgavtvawkadsspvkagvetttpskgsnnk yaassylsltpeqwkshrsyscqvthegstvektvaptecs HeavychainB rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwik SEQID pqygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygd NO:179 sswaldawgqgttvvvsadkthtQvhltqsgpevrkpgtsvkvsckapgnt lktydlhwvrsvpgqglqwmgwishegdkkviverfkakvtidwdrstnt aylqlsgltsgdtavyycakgskhrlrdyalydddgalnwavdvdylsnlef wgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgclvkdyfpepv tvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsn tkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevt cvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlh qdwlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltkn qvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvd ksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdflkisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:180 t yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtrtvaapsvfifp psdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysls stltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein23NucleotideSequences HeavychainA gaggttagactggtggagtcaggaggggggcagtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:181 cctccagataagggactagagtgggtgggaagaatcacagatccagacgagggctg gtccgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttaggtccggctatccccaggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgcgtcgaccaagggccc cagcgtgttccactggcccctagcagcaagageacataggcggaacagccgccct gggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctagaattaggcg ccctgaccagcggcgtgcacacctttccagctgtgctgcagtccagcggcctgtacag cctgagcagcgtcgtgacagtgcccagcagctctctgggcacccagacctacatctgc aacgtgaaccacaageccageaacaccaaggtggacaagaaggtggaacccaaga gctgcgacaagacccacacctgtcccccttgtcctgcccccgaactgagggaggccc ttccgtgttcctgttccccccaaagcccaaggacaccctgatgatcaaccggaccccca aagtgacctgcgtggtggtagatgtgtcccacgaggaccctgaagtgaagttcaattgg tacgtggacggcgtggaagtgcacaacgccaagaccaagccaagagaggaacagta caacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaac ggcaaagagtacaagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaa accatcagcaaggccaagggccagccccgcgaaccccaggtgtgcacactgccccc aagcagggacgagagaccaagaaccaggtgtccctgagagtgccgtgaaaggctt ctacccctccgatatcgccgtagaatgggagagcaacagccagcccgagaacaacta caagaccaccccccctatgaggacagcgacgactcattatcaggtatccaagaga cagtggacaagtcccggtggcagcagggcaacgtgttcagctgctccgtgatgcacg aggcccggcacaaccactacacccagaagtccctgagcctgagccccggcaag LightchainA gcatccgaactgactcaggaccctgccgtetctgtggcactgaagcagactgtg SEQID actattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga NO:182 agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggcca tctggcatccccgaccgcttttctggcagtgcatcagggaaccgagccagtctg accattaccggcgcccaggctgaggacgaagccgattactattgcagctcccg ggataagagcggctccagactgagcgtgttcggaggaggaactaaactgacc gtcctcagtcagcccaaggctgccccctcggtcactctgttcccgccctcgagt gaggagatcaagccaacaaggccacactggtgtgtctcataagtgacttctac ccgggagccgtgacagtggcaggaaggcagatagcagccccgtcaaggcg ggagtggagaccaccacaccctccaaacaaagcaacaacaagtacgcggcc agcagctacctgagcctgacgcctgagcagtggaagtcccacagaagctaca gctgccaggtcacgcatgaagggagcaccgtggagaagacagtggccccta cagaatgttca HeavychainB agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcag NO:183 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcgcctacatagacatccggggcctgaagcccgatgacaccgccgtgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatacttggggccagggc acaaccgtggtggtgtctgccgacaaaacccatacccaggtgcacctgacacagagc ggacccgaagtgcggaagcctggcacctctgtgaaggtgtcctgcaaggcccctggc aacaccctgaaaacctacgacctgcactgggtgcgcagcgtgccaggacagggactg cagtggatgggctggatcagccacgagggcgacaagaaagtgatcgtggaacggttc aaggccaaagtgaccatcgactgggacagaagcaccaacaccgcctacctgcagctg agcggcctgacctctggcgataccgccgtgtactactgcgccaagggcagcaagcac cggctgagagaetacgccctgtacgacgatgacggcgccctgaactgggccgtggat gtggactacctgagcaacctggaattctggggccagggcacagccgtgaccgtgtcat ctgataagacccacaccgcttccaccaagggcccatcggtcttccccctggcaccctcc tccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttcc ccgaaccggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacacct tcccggctgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccct ccagcagcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaaca ccaaggtggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccacc gtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaaccca aggacaccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgag ccacgaagaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatg ccaagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtc ctcaccgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctcca acaaagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccc cgagaaccacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaa gtcagcctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtggg agagcaatgggcagccggagaacaactacaagaccacgcctcccgtgctggactcc gacggctccttcttcctctactcaaaactcaccgtggacaagagcaggtggcagcagg ggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgcagaag agcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgaga SEQID gcgccagcatcagctgcaagagcagccactccctgatccacggcgaccggaa NO:184 caactacctggcttggtacgtgcagaagcccggcagatccccccagctgctga tctacctggccagcagcagagccagcggcgtgcccgatagattttctggcagc ggcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgaggac gtgggcacctactactgtatgcagggcagagagagcccctggacctttggcca gggcaccaaggtggacatcaaggacaaaacccatacctacatccacgtgacc cagagccccagcagcctgtccgtgtccatcggcgacagagtgaccatcaactg ccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaagcct ggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggc gtgcccagcagattaccggcagcggcttccacaccagcttcaacctgaccatc agcgatctgcaggccgacgacattgccacctactattgtcaggtgctgcagttct tcggcagaggcagcagactgcacatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccg gcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaa gtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaag cgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctg acactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtga cccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtg t BindingProtein24AminoAcidSequences HeavychainA evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgritgpge SEQID gwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyydfwsgypp NO:185 geeyfqdwgqgtlvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvs wnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkve pkscdkthtcppcpapellggpsvflfppkdtlmisrtpevtcvvvdvshedpev kfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkal papiektiskakgqprepqvctlppsrdeltknqvslscavkgfypsdiavewesngq pennykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslsls pg LightchainA aseltqdpavsvalkqtvtitcrgdslrshyaswygkkpgqapvllfygknnrpsgip SEQID drfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvlsqpkaapsv NO:186 tlfppsseelqankatlvclisdfypgavtvawkadsspvkagvetttpskqsnnkya assylsltpeqwkshrsyscqvthegstvektvaptecs HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmg SEQID wishegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskh NO:187 rlrdyalydddgalnwavdvdylsnlefwgqgtavtvss dkthtrahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewv gwikpqygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrs ygdsswaldawgqgttvvvsadkthlastkgpsvfplapsskstsggtaalgc lvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtl misrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyr vvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffl yskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainB yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtdfvltqsphsls NO:188 vtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassrasgvpdrfsgsg sdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikdkthtrtvaapsvfifpp sdeqlksgasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein24NucleotideSequences HeavychainA gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgcc SEQID tgagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcagcc NO:189 tccagataagggactggaatgggtgggaagaatcacagatccaagcgagggctggtc cgtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaataccaaga ataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttctgtgc cagaacaggcaaatactacgacactggtccggctatccccctggcgaggaatattttca agactggggtcagggaacccttgttatcgtgtcctccgcgtcgaccaagggccccagcg tgttccctctggcccctagcagcaagagcacataggcggaacagccgccctgggctg cctcgtgaaggactactttcccgagcccgtgaccgtgtcaggaattaggcgccagac cagcggcgtgcacacctttccagagtactacaatccagcggcctatacaacctgagca gcgtcgtgacagtgcccagcagctactgggcacccagacctacatagcaacgtgaac cacaagcccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaa gacccacacctgtcccccagtcctgcccccgaactgctgggaggcccttccgtgacct gttccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgc gtggtggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacgg cgtggaagtgcacaacgccaagaccaagccaagagaggaacagtacaacagcaccta ccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtac aagtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaagg ccaagggccagecccgcgaaccccaggtgtgcacactgcccccaagcagggacgag ctgaccaagaaccaggtgtccctgagagtgccgtgaaaggatctacccaccgatatc gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccc tgtgctggacagcgacggctcattcttcctgatgtccaagctgacagtagacaaatccca gtggcagcagggcaacgtgttcagctgaccgtgatgcacgaggccctgcacaaccac tacacccagaagtccctgagcctgagccccggcaag LightchainA gcatccgaactgactcaggaccctgccgtctctgtggcactgaagcagactgtg SEQID actattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga NO:190 agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccat ctggcatccccgaccgcattctggcagtgcatcagggaaccgagccagtctga ccattaccggcgcccaggctgaggacgaagccgattactattgcagctcccgg gataagagcggctccagactgagcgtgttcggaggaggaactaaactgaccgt cctcagtcagcccaaggctgccccctcggtcactagttcccgccctcgagtgag gagcttcaagccaacaaggccacactggtgtgtctcataagtgacttctacccgg gagccgtgacagtggcctggaaggcagatagcagccccgtcaaggcgggagt ggagaccaccacaccctccaaacaaagcaacaacaagtacgcggccagcagc tacctgagcctgacgcctgagcagtggaagtcccacagaagctacagctgcca ggtcacgcatgaagggagcaccgtggagaagacagtggcccctacagaatgtt ca HeavychainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtga SEQID ccatcaactgccagacctacagggcgtgggcagcgacctgcactggtatcagcacaa NO:191 gcctggcagagcccccaagagagatccaccacacaagcagcgtggaagatggcgt gcccagcagattaccggcagcagatccacaccagatcaacctgaccatcagcgatct gcaggccgacgacattaccacctactattgtcaggtgctgcagttctteggcagaggca gcagactgcacatcaaggacaaaacccataccgacttcgtgctgacccagagccctca cagcctgagcgtgacacctggcgagagcgccagcatcagagcaagagcagccactc cctgatccacggcgaccggaacaactacctggcttggtacgtgcagaagcccggcaga tccccccagctgctgatctacctggccagcagcagagccagcggcgtgcccgatagatt ttctggcagcagcagcgacaaggacttcaccctgaagatcagccgggtggaaaccga ggacgtgggcacctactactgtatgcagggcagagagagcccaggacctaggccag ggcaccaaggtggacatcaaggataagacccatacccgtacggtggccgctcccagc gtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgc ctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccc tgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacc tacagcctgagcagcaccagacactgagcaaggccgactacgagaagcacaaggtg tacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagatcaacc ggggcgagtgt LightchainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacag SEQID agtgaccatcaactgccagacctctcagggcgtgggcagcgacctgcactggt NO:192 atcagcacaagcctggcagagcccccaagctgagatccaccacacaagcagc gtggaagatggcgtgcccagcagattttccggcagcggcttccacaccagcttc aacctgaccatcagcgatctgcaggccgacgacattgccacctactattgtcagg tgctgcagttcttcggcagaggcagcagactgcacatcaaggacaaaacccata ccgacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgag agcgccagcatcagctgcaagagcagccactccctgatccacggcgaccgga acaactacctggcttggtacgtgcagaagcccggcagatccccccagctgctga tctacctggccagcagcagagccagcggcgtgcccgatagattttctggcagcg gcagcgacaaggacttcaccctgaagatcagccgggtggaaaccgaggacgt gggcacctactactgtatgcagggcagagagagcccctggacctttggccagg gcaccaaggtggacatcaaggataagacccatacccgtacggtggccgctccc agcgtgttcatcttccacctagcgacgagcagctgaagtccggcacagcact gtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaag gtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcag gacagcaaggactccacctacagcctgagcagcaccctgacactgagcaagg ccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcct gtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein25AminoAcidSequences HeavychainA qvqlvqsggqmkkpgesmriscrasgyefi wirlapgkrpewmg SEQID rvtmtrdvysdtaflelrsltvddtavyfctr wgr NO:193 gtpvivssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvh tfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcp pcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgve vhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskak gqprepqvctlppsrdeltknqvslscavkgfypsdiavewesgqpennykttppv ldsdgsfflvskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainA eivltqspgtlslspgetaiisc awyqqrpgqaprlviy gipdrfs SEQID gsrwvgpdynltisnlesgdfgvyy fgqgtkvqvdikrtvaapsvfifppsde NO:194 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltls kadyekhkvyacevthqglsspvcksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgrit SEQID gpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyy NO:195 dfwsgyppgeeyfqdwgqgtlvivssdkthtqvqlvesgggvvqpgtslrls caasqfrfdgygmhwvrqapgkglewvasishdgikkyhaekvwgrftisr dnskntlylqmnslrpedtalyycakdlredeceewwsdyydfgkqlpcaks rgglvgiadnwgqgtmvtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyic nvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvtlfppkpkdtl misrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyr vvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffl yskltvdksrwqqgnvfscsvlhealhshylqkslslspg LightchainB qsvltqppsvsaapgqkvtiscsgntsnignnfvswyqqrpgrapqlliyetdkrpsgi SEQID pdrfsasksgtsgtlaitgtqtgdeadyycatwaaslssarvfgtgtkvivldkthtaselt NO:196 gdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsg sasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfif ppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysl sstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein25NucleotideSequences HeavychainA cagatgcagctggtgcagtctggcggccagataaaaaaacccagcgagaacatgcgg SEQID atcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcagact NO:197 ggcccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagccgt gaactacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacagcgat accgccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttctgcacc cggggcaagaactgcgactacaactgggacttcgagcactggggcagaggcacccct gtgatcgtatcaagcgcgtcgaccaagggccccagcgtgttccactaacccctagcaa caagagcacataggcagaacaaccaccctaggctgcctcgtgaaggactactttcccg agcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcacaccatcca gctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtgacagtgcccagca gctactaggcacccagacctacatagcaacgtgaaccacaagcccagcaacaccaa ggtggacaagaaggtggaacccaagagagcgacaagacccacacagtcccccttgt cctgcccccgaactgagggaggcccttccgtgacctgttccccccaaagcccaagga caccctgatgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccacg aggaccctgaagtgaagttcaattggtacgtggacggcgtggaagtgcacaacgccaa gaccaagccaagagaggaacagtacaacagcacctaccgggtggtgtccgtgctgac cgtgctgcaccaggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaag gccctgcctgcccccatcgagaaaaccatcagcaaggccaagggccagccccgcgaa ccccaggtgtacacactgcccccaaacagggacgaactaaccaagaaccaaatgtcc ctgagctgtgccgtgaaaggcttctacccctccgatatcgccgtggaatgggagagcaa cggccagcccgagaacaactacaagaccaccccccctgtgctggacagcgacggctc attcttcctggtgtccaagctgacagtggacaagtcccggtggcagcagggcaacgtgtt cagctgctccgtgctgcatgaggctctgcacagccactacacgcagaagagcctctccc tgtctccgggt LightchainA Gagatcgtgctgacacagagccaggcaccctgagcctgtctccaggegagacagcc SEQID atcatcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcctg NO:198 gacaggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccccg atagattcagcggctccagatggaaccctaactacaacctgaccatcagcaacctgaaa agcggcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggcaccaa ggtgcaggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctag cgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctaccc ccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagcc aggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagcacc ctgacactgagcaagaccgactacgagaaacacaaggtgtacgcctacgaagtgacc caccagggcctatctagccccgtgaccaagagcttcaaccagggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgcct SEQID gagctgactgcctccggattgatacgataacgcctggatgacctgggtcaggcagcct NO:199 ccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctggtcc gtggactacgcggaatctgtaaagggcggnacaatctcaagggacaataccaagaat accttgtatttgaagatgaacaacgtaagaactgaagacaccagatattacttctatgcca gaacagacaaatactacgacttctggtccagctatccccctggcgaggaatattttcaaa actggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccaggtgcagt tggtggagtctgggggaggcgtggtccagcctgggacgtccctgagactctcctgtgca gcactcaattcaggtttgatggttatggcatgcactgggtccgccaggccccaggcaag gggctggagtgggtggcatctatatcacatgatggaattaaaaagtatcacgcagaaaaa gtgtggggccgcttcaccataccagagacaattccaagaacacactgtatctacaaatg aacagcctgcgacctgaggacacggctctctactactgtgcgaaagatttgcgagaaga cgaatgtgaagagtggtggtcggattattacgattttgggaaacaactcccttgcgcaaag tcacgcggcggcttggttggaattgctgataactggggccaagggacaatggtcaccgt ctcttcagataagacccacaccgcttccaccaagggcccatcggtcttccccctggcacc ctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactac ttccccgaaccggtgacggtgtcgtggaactcaggcgccagaccagcggcgtgcaca ccttcccagagtcctacagtcctcaggactctactccctcagcagcgtagtgaccatgc cctccagcagatggacacccagacctacatagcaacgtgaatcacaagcccagcaac accaaggtggacaagaaagttgagcccaaatcttgtgacaaaactcacacatgcccacc gtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaa ggacaccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagcc acgaagaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgcc aagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctc accgtcagcaccaggactggctgaatgacaaggagtacaagtacaaggtaccaaca aagccacccaacccccatcgagaaaaccatctccaaagccaaagagcaaccccgag aaccacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagca atgggcagccggagaacaactacaagaccacgcctcccgtgaggactccgacggctc cttcttcactactcaaaactcaccgtggacaagagcaggtggcagcaggggaacgtat ctcatgctccgtgctgcatgaggctctgcacagccactacacgcagaagagcctctccct ataccgggt LightchainB cagtctgtgctgacgcagccgccctcagtgtctgcsgccccaggacagaaggt SEQID caccatctcctgactggaaacacctccaacattggcaataattttgtgtcctggtat NO:200 caacagcgccccggcagagccccccaactcctcatttatgaaactgacaagcga ccctcagggattcctgaccgattctctgcttccaagtctggtacgtcaggcaccct ggccatcaccgggctgcagactggggacgaggccgattattactgcgccacat gggctgccagectgagaccgcgcgtgtcttcggaactgggaccaaggtcatcg tcctggacaaaacccataccgcatccgaactgactcaggaccctgccgtctctgt ggcactgaagcagactgtgactattacttgccgaggcgactcactgcggagcca ctacgcttcctggtatcagaagaaacccggccaggcacctgtgctgctgttctac ggaaagaacaataggccatctggcatccccgaccgcttttctggcagtgcatcag ggaaccgagccagtctgaccattaccggcgcccaggctgctggacgaagccga ttactattgcagctcccgggataagagcggctccagactgagcgtgttcggagg aggaactaaactgaccgtcctcgataagacccatacccgtacggtggccgctcc cagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctct gtcgtgtgcctgagaacaacttctacccccgcgaggccaaagtgcagtggaag gtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcag gacagcaaggactccacctacagcctgagcagcaccctgacactgagcaagg ccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcct gtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein26AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts lfwfrqapgrglewvgw SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar wg NO:201 qgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgv htfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtc ppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgv evhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiska kgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpennykttpp vldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqts lhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgf fnltisdlqaddiatyyc rgsrlhikrtvaapsvfifppsdeql NO:202 ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlska dyekhkvyacevthqglsspvtksfnrgec HeavychainB evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgrit SEQID gpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgkyy NO:203 dfwsgyppgeeyfqdwgqgtlvivssdkthtqvqlvesgggvvqpgtslrls caasqfrfdgygmhwvrqapgkglewvasishdgikkyhaekvwgrftisr dnskntlylqmnslrpedtalyycakdlredeceewwsdyydfgkqlpcaks rgglvgiadnwgqgtmvtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyic nvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvtlfppkpkdtl misrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyr vvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp crdeltknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffl yskltvdksrwqqgnvfscsvlhealhshylqkslslspg LightchainB qsvltqppsvsaapgqkvtiscsgntsnignnfvswyqqrpgrapqlliyetdkrpsgi SEQID pdrfsasksgtsgtlaitgtqtgdeadyycatwaaslssarvfgtgtkvivldkthtaselt NO:204 gdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdrfsg sasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaapsvfif ppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysl sstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein26NucleotideSequences HeavychainA agagcccacctggtgcagtaggcaccgccatgaagaaaccaggcgcctagtgcggg SEQID tgtcctgtcagacaagcggctacaccttcaccgcccacatcctgactggaccggcagg NO:205 cccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtgaa cttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgagatc gcctacatagacatccggggcctaaaacccgatgacaccaccatgtactactgcgcca gagacagaagctacggcgacagcagctgaactctagatacttgggaccagggcacaa ccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccctagca gcaagagcacatctggcggaacagccgccctgggctgcctcgtgaaggactactttccc gagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtgcacacctttcc agctgtgctgcagtccagcggcctgtacaacctgagcagcgtcgtgacgtgcccagc agctctctggacacccagacctacatctgcaacgtgaaccacaagcccagcaacacca aggtggacaagaaggtggaacccaagagctgcgacaagacccacacctgtcccccttg tcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaaagcccaaaga caccctgatgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccacg aggaccctgaagtgaagttcaattggtacgtggacggcgtggaagtgcacaacgccaa gaccaagccaagagaggaacagtacaacagcacctaccgggtggtatccgtgctgac cgtactacaccaggactagctgaacggcaaagagtacaagtgcaagatgtccaacaag gccagcctgcccccatcgagaaaaccatcagcaaggccaagggccagccccgcgaa ccccaggtgtgcacactgcccccaagcagggacgagatgaccaagaaccaggtatcc ctgagctgtgccgtgaaaggcttctacccaccgatatcgccgtggaatgggagagcaa cggccagcccgagaacaactacaagaccaccccccctgtgctggacagcgacggctc attcttcctgatgtccaagctaacagtagacaaatcccagtggcagcagggcaacatgtt cagctgctccgtgctgcatgaagctctacacagccactacacgcagaagagcctctccc tgtctccgggt LightchainA tacatccacatgacccaaagccccaacagcctgtccatgtccatcggcaacagagtga SEQID ccatcaactgccaaacactcaggacgtaggcagcaacctacactgatatcagcacaa NO:206 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtgaaaaatgacgt gcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatct gcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggcag cagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcacccacctagcga cgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccg cgaggccaaagtacagtggaagatggacaacaccctacagagcggcaacagccagg aaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctga cactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccacc agggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgcct SEQID gagctgttctgcctccggctttgatttcgataacgcctggatgacctgggtcaggcagcct NO:207 ccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctggtcc gtggactacgcggaatctgttaaagggcggtttacaatctcaagggacaataccaagaat accttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttctgtgcca gaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatattttcaag actggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccaggtgcagt tggtggagtctgggggaggcgtggtccagcctgggacgtccctgagactctcctgtgca gcctctcaattcaggtttgatggttatggcatgcactgggtccgccaggccccaggcaag gggctggagtgggtggcatctatatatcatgatggaattaaattagtatcacgcagaaaaa gtgtggggccgcttcaccatctccagagacaattccaagaacacactgtatctacaaatg aacagcctgcgacctgaggacacggctctctactactgtgcgaaagatttgcgagaaga cgaatgtgaagagtggtggtcggattattacgattttgggaaacaactcccttgcgcaaag tcacgcggcggcttggttggaattgctgataactggggccaagggacaatggtcaccgt ctcttcagataagacccacaccgcttccaccaagggcccatcggtcttccccctggcacc ctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcattggactac ttccccgaaccggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcaca ccttcccggctgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgc cctccagcagcttgggcacccagacctacatctgcaacgtgaattacaagcccagcaac accaaggtggacaagaaagttgagcccaaatcttgtgacaaaacicacacatgcccacc gtgcccagcacctgaactcctggggggaccgtcttgtcttcctcttccccccaaaacccaa ggacaccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagcc acgaagaccctgaggtcaagttcaactggtatgttgacggcgtggaggtgcataatgcc aagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcgtcctc accgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaaca aagccctcccagcccccatcgagaaaaccatctccaaagccaaagggcagccccgag aaccacaggtgtacaccctgcccccatgccgggatgagctgaccaagaatcaagtcag cctgtggtgcctggtaaaaggcttctatcccagcgacatcgccgtggagtgggagagca atgggcagccggagaacaactacaagaccacgcctcccgtgctggactccgacggctc cttcttcctccactcaaaactcaccgtggacaagagcaggtggcagcaggggaacgtctt ctcatgctccgtgctgcatgaggctctgcacagccactacacgcagaagagcctctccct gtctccgggt LightchainB cagtctgtgctgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccat SEQID ctcctgactggaaacacctccaacattggcaataattagtgtcctggtatcaacagcgcc NO:208 ccggcagagccccccaactcctcatttataaaactgacaagcgaccctcagggattcctg accgattctctgcttccaagtctggtacgtcaggcaccctggccatcaccgggctgcaga ctggggacgaggccgattattactgcgccacatgggctgccagcctgagttccgcgcgt gtcttcggaactgggaccaaggtcatcgtcctggacaaaacccataccgcatccgaact gactcaggaccctgccgtactgtggcactgaagcagactgtgactattacttgccgagg cgactcactgcggagccactacgcttcaggtatcagaagaaacccggccaggcacct gtgctgagttctacggaaagaacaataggccataggcatccccgaccaatttaggca gtgcatcagggaaccgagccagtctgaccattaccggcgcccaggctgaggacgaag ccgattactattgcagctcccgggataagagcggctccagactgagcgtgttcggagga ggaactaaactgaccgtcctcgataagacccatacccgtacggtggccgctcccagcgt gttcatatcccacctagcgacgagcagctgaagtccggcacagcctagtcgtgtgcct gctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctg cagagcggcaacaaccaggaaagcgtgaccgagcaggacagcaaggactccaccta cagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgta cgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccgg ggcgagtgt BindingProtein27AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts lfwfrqapgrglewvgw SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar wg NO:209 qgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgv htfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtc ppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgv evhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiska kgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpennykttpp vldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsdeq NO:210 lksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlsk adyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgri SEQID tgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgky NO:211 ydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsvk vsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkakvti dwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwavdvd ylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgclvkdy fpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnh kpsntkvdkkvepkscdkthtcppcpapellggpsvilfppkpkdtlmisrtp evtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltv lhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppcrdeltk nqvslwclvkgfypsdiavevvesngqpennykttppvldsdgsfllyskltv dksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassra SEQID sgvpdrfsgsgsdkdftikisrvetedvgtyycmqgrespwtfgqgtkvdikdkthta NO:212 seltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgipdr fsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdst yslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein27NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatccgttctggttccggcag NO:213 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgt gaacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcga gatcacctacatagacatccagggcctaaaacccgatgacaccaccatgtactactgc gccagagacagaagctacggcgacagcagctgggctctggatgcttggggccaggg cacaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggccc ctagcagcaagagcacatctggcggaacagccgccagggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaattaggcgccctgaccagcgggtgca cacctttccagctatgctgcagtccagcaacctgtacagcctaagcagcgtcgtgaca atgcccagcagctactgggcacccagacctacatctacaacatgaaccacaaaccca gcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacac ctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttcccccc aaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggt ggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagccaagagaaaaacaatacaacagcacctaccaggt ggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtg caaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaa gggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctg accaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgc cgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctg tgctgaacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccga tggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtaacccagaaccccagcagcctatccgtatccatcgacgacaaagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:214 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttccagagaccatcagcgatc tgcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggc agcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctag cgacgagcagagaagtccggcacagcctctgtcgtgtgcctgagaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacag ccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagca ccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtga cccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgactgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:215 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtgactacgcggaatctgttaaaggcggatacaatctcaaggpacaatacca agaataccttgtatttgaagatgaacaacgtaagaactgaagacaccaaatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccagttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggtg tcctgcaaggcccctagcaacaccctgaaaacctacgacctgcactgggtgcgcagc gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaaga aagtgatcgtggaacagttcaaggccaaaatgaccatcgactaagacagaagcacca acaccgcctacctgagctgagcggcctgacctctggcgataccgccgtgtactactg cgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcg ccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccagg gcacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagagcccatc ggtcttccccctggcaccctcctccaagagcacctctgggaacacaacggccctgaa ctgcctgatcaagaactacttccccaaaccaatgacggtgtcgtaaaactcagacgcc ctgaccagcggcatgcacaccttcccggagtcctacaatcctcaaaactctactccct cagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaac gtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtg acaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcag tcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtagtgaacatgagccacgaagaccctgaggtcaaattcaactggtatgtt gacggcgtgaaggtgcataatgccaagacaaagccgcaggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctagtaaaaggcttctatccc agcgacatcgccatggagtgagagagcaataggcagccggagaacaactacaaga ccacgcctcccgtgaggactccgacggctccttcacctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:216 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcaaccgggtagaaaccgaggacgtaggcacctactactgtatgcagg gcagagagagcccctggacctttagccaggacaccaagatggacatcaagaacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccg gcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagt ccggcacagcactgtcgtgtacctgagaacaacttctacccccgcgagaccaaagt gcagtggaaggtggacaacaccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein28AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts lfwfrqapgrglewvgw SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar NO:217 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsde NO:218 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgky NO:219 ydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsv kvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkak vtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwav dvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdt lmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynsty rvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlp pcrdeltknqvslwclvkgfypsdiavevvesngqpennykttppvldsdgs fllyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftikisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:220 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein28NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggca NO:221 ggcccctcgcagaggactggaatgggtggatggatcaagccccagtatggcgccg tgaacttcagcggaggcaccaggatagagtaaccagacccgggacgtgtaccacg agatcgcctacatggacatccggggcctgaagcccgatgacaccgccgtgtactactg cgccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagg gcacaaccgtggtggtgtagccgcctctacaaagggccccagcgtgttccactggc ccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtggagg actactttcccgagcccatgaccatgtcctggaattaggcaccctgaccagcggcgtg cacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtga cagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagc ccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagaccca cacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccc cccaaagcccaaagacaccctgatgatcagccggacccccgaagtaacctacgtggt ggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacgacgtg gaagtgcacaacgccaagaccaagccaagagaaaaacaatacaacagcacctacc gggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtaca agtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaagg ccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacga gctgaccaagaaccaggtatccctgaactatgccgtgaaaggcttctacccctccgata tcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccc cctgtgctggacaacgacggctcattcttcctagtgtccaaactgacagtggacaagtc ccggtggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacag ccactacacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtaacccagaaccccagcagcctatccgtatccatcgacgacaaagtg SEQID accatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcac NO:222 aagcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagaagg cgtgcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagc aatctgcaggccgacgacattgccacctactattgtcaggtactgcagttcttcggcaaa ggcagcagactgcacatcaagcgtacaatggccgctcccagcgtgttcatcttcccac ctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaactt ctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggc aacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctga gcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgc gaagtgacccaccagagcctgtctagccccgtaaccaagaacttcaaccggagcga gtgt HeavychainB gaggttagactggtggaatcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgttctgcaccagctttgatttcgataacgcctggatgacctgggtcagacaa NO:223 cctccaggtaagggactaaagtgggtaggaagaatcacaggtccaggcgaaggctg gtccatggactacacggaatctgttaaagggcggtttacaatctcaaaggacaatacca agaataccttgtatttggagatgaacaacgtgagaactgaagacaccggatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccttgttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcgaaaacctggcacctagtgaaggt gtcctgcaagacccaggcaacaccctgaaaacctacgacctgcactggatgcgcag cgtaccaggacaaggactgcaatggatgggctgaatcagccacgagggcgacaag aaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcacc aacaccgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtactact gcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacgg cgccctgaactgagccgtggatgtggactacctgagcaacctggaattaggggccag ggcacagccatgaccgtgtcatctgataagacccacaccgcttccaccaagggcccat cggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgg gctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgc cctgaccagcggcgtgcacaccttcccggagtcctacagtcctcaggactctactccc tcagcagcgtagtgaccgtgccctccaacagcttgggcacccagacctacatctgcaa cgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgt gacaaaactcacacatgcccaccgtgcccagcacctaaactcctggggaaaccgtca gtcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggt cacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggtat gttgacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaa cagcacgtaccgtgtggtcaacgtcctcaccgtcctgcaccaggactggctgaatgac aaggaatacaagtacaaggtaccaacaaagccctcccagcccccatcgagaaaacc atctccaaagccaaagggcagccccgagaaccacaggtgtacaccctacccccatgc cgggatgagctgaccaagaatcaagtcagcctgtggtgcctggtaaaaggcttctatcc cagcgacatcgccgtggagtgggagagcaatgggcagccggagaacaactacaag accacgcctcccgtgctggactccgacggctccttcttcctctactcaaaactcaccgtg gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctc tgcacagccactacacgcagaagagcctaccagtctccggat LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:224 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcdgcccgatagatataggcagcggcagcgacaaggacttca ccctgaagatcagccgaatggaaaccaaggacatgggcacctactactgtatacagg gcagagagagcccaggacctttggccagggcaccaaggtggacatcaaggacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccaaccgcttttctggcaatgcatcagagaaccaagccagtctgaccattaccg gcacccaagagaggacaaaaccaattactattacaactcccgggataagagcgact ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaag tccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagt gcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcggacc gagcaagacagcaaggactccacctacagcctgaacaacaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein29AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts lfwfrqapgrglewvgw SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar NO:225 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedav SEQID psrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsde NO:226 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:227 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsv kvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkak vtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwav dvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdt lmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynsty rvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlp pcrdeltknqvslwclvkgfypsdiavevvesngqpennykttppvldsdgs fllyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftikisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:228 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein29NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatccgttctggttccggcag NO:229 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcacctacatagacatccagggcctaaaacccgatgacaccaccatgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccagggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattaggcgccctgaccagcgggtgcac acctttccagctatgctgcagtccagcaacctgtacagcctaagcagcgtcgtgacagt gcccagcagctactgggcacccagacctacatctacaacatgaaccacaaacccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaaaaacaatacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctgaacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtaacccagaaccccagcagcctatccgtatccatcgacgacaaagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:230 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttccagagaccatcagcgatc tgcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggc agcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctag cgacgagcagagaagtccggcacagcctctgtcgtgtgcctgagaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacag ccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagca ccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtga cccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgactgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:231 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtgactacgcggaatctgttaaaggcggatacaatctcaaggpacaatacca agaataccttgtatttgaagatgaacaacgtaagaactgaagacaccaaatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccagttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggtg tcctgcaaggcccctagcaacaccctgaaaacctacgacctgcactgggtgcgcagc gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaaga aagtgatcgtggaacagttcaaggccaaaatgaccatcgactaagacagaagcacca acaccgcctacctgagctgagcggcctgacctctggcgataccgccgtgtactactg cgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcg ccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccaggg cacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagagcccatcg gtcttccccctggcaccctcctccaagagcacctctgggaacacaacggccctgggct gcctgatcaagaactacttccccaaaccaatgacggtgtcgtaaaactcagacgccct gaccagcggcatgcacaccttcccggagtcctacaatcctcaaaactctactccctca gcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgt gaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagt cttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtagtgaacatgagccacgaagaccctgaggtcaaattcaactggtatgtt gacggcgtgaaggtgcataatgccaagacaaagccgcaggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctagtaaaaggcttctatccc agcgacatcgccatggagtgagagagcaataggcagccggagaacaactacaaga ccacgcctcccgtgaggactccgacggctccttcacctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgcc SEQID agcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctg NO:301 gcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagca gcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttca ccctgaagatcaaccgggtagaaaccgaggacgtaggcacctactactgtatgcagg gcagagagagcccctggacctttagccaggacaccaagatggacatcaagaacaaa acccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcaga ctgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcaga agaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctgg catccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattaccg gcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggct ccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccatac ccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagt ccggcacagcactgtcgtgtacctgagaacaacttctacccccgcgagaccaaagt gcagtggaaggtggacaacaccctgcagagcggcaacagccaggaaagcgtgacc gagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagcaa ggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgt ctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein30AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts lfwfrqapgrglewvgwi SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar NO:232 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedav SEQID psrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsde NO:233 qlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:234 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsv kvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkak vtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwav dvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdt lmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynsty rvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlp pcrdeltknqvslwclvkgfypsdiavevvesngqpennykttppvldsdgs fllyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftikisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:235 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein30NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatccgttctggttccggcag NO:236 gcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtg aacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgag atcacctacatagacatccagggcctaaaacccgatgacaccaccatgtactactgcg ccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagggc acaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggcccc tagcagcaagagcacatctggcggaacagccgccagggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaattaggcgccctgaccagcgggtgcac acctttccagctatgctgcagtccagcaacctgtacagcctaagcagcgtcgtgacagt gcccagcagctactgggcacccagacctacatctacaacatgaaccacaaacccag caacaccaaggtggacaagaaggtggaacccaagagctgcgacaagacccacacct gtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccccccaa agcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtggtgg atgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtggaagt gcacaacgccaagaccaagccaagagaaaaacaatacaacagcacctaccgggtg gtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgc aaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaaggccaag ggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacgagctga ccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgatatcgcc gtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgt gctgaacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtcccggt ggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacagccact acacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtaacccagaaccccagcagcctatccgtatccatcgacgacaaagtga SEQID ccatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaa NO:237 gcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttccagagaccatcagcgat ctgcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagagg cagcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccaccta gcgacgagcagagaagtccggcacagcctctgtcgtgtgcctgagaacaacttctac ccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaaca gccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcag caccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagt gacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgactgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:238 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtgactacgcggaatctgttaaaggcggatacaatctcaaggpacaatacca agaataccttgtatttgaagatgaacaacgtaagaactgaagacaccaaatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccagttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggtg tcctgcaaggcccctagcaacaccctgaaaacctacgacctgcactgggtgcgcagc gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaaga aagtgatcgtggaacagttcaaggccaaaatgaccatcgactaagacagaagcacca acaccgcctacctgagctgagcggcctgacctctggcgataccgccgtgtactactg cgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcg ccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccaggg cacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagagcccatcg gtcttccccctggcaccctcctccaagagcacctctgggaacacaacggccctgggct gcctgatcaagaactacttccccaaaccaatgacggtgtcgtaaaactcagacgccct gaccagcggcatgcacaccttcccggagtcctacaatcctcaaaactctactccctca gcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgt gaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtga caaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagt cttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggtca catgcgtggtagtgaacatgagccacgaagaccctgaggtcaaattcaactggtatgtt gacggcgtgaaggtgcataatgccaagacaaagccgcaggaggagcagtacaaca gcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggcaa ggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaaccat ctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgcc gggatgagctgaccaagaatcaagtcagcctgtggtgcctagtaaaaggcttctatccc agcgacatcgccatggagtgagagagcaataggcagccggagaacaactacaaga ccacgcctcccgtgaggactccgacggctccttcacctctactcaaaactcaccgtgg acaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctct gcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB Gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgc SEQID cagcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacct NO:239 ggcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagc agcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttc accctgaagatcaaccgggtagaaaccgaggacgtaggcacctactactgtatgcag ggcagagagagcccctggacctttagccaggacaccaagatggacatcaagaacaa aacccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcag actgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcag aagaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctg gcatccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattacc ggcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcggc tccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccata cccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaa gtccggcacagcactgtcgtgtacctgagaacaacttctacccccgcgagaccaaa gtgcagtggaaggtggacaacaccctgcagagcggcaacagccaggaaagcgtga ccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgagc aaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcct gtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein31AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqts ilfwfrqapgrglewvgw SEQID nfgggfrdrvtltrdvyreiaymdirglkpddtavyycar NO:240 wgqgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgal tsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscd kthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnw yvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapi ektiskakgqprepqvetlppsrdeltknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqqgnvfscsvmhealhnhytqkslslspg LightchainA Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssveda SEQID vpsrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsd NO:241 eqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Evrlvesggglvkpggslrlscsasgfdfdnawmtwvrqppgkglewvgr SEQID itgpgegwsvdyaesvkgrftisrdntkntlylemnnvrtedtgyyfcartgk NO:242 yydfwsgyppgeeyfqdwgqgtlvivssdkthtqvhltqsgpevrkpgtsv kvsckapgntlktydlhwvrsvpgqglqwmgwishegdkkviverfkak vtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddgalnwav dvdylsnlefwgqgtavtvssdkthtastkgpsvfplapsskstsggtaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyi cnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdt lmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynsty rvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlp pcrdeltknqvslwclvkgfypsdiavevvesngqpennykttppvldsdgs fllyskltvdksrwqqgnvfscsvlhealhshytqkslslspg LightchainB dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassr SEQID asgvpdrfsgsgsdkdftikisrvetedvgtyycmqgrespwtfgqgtkvdikdkth NO:243 taseltqdpavsvalkqtvtitcrgdslrshyaswyqkkpgqapvllfygknnrpsgi pdrfsgsasgnrasltitgaqaedeadyycssrdksgsrlsvfgggtkltvldkthtrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteq dskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein31NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgg SEQID gtgtcctgtcagacaagcggctacaccttcaccgcccacatccgttctggttccggca NO:244 ggcccctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccg tgaacttcggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcg agatcacctacatagacatccagggcctaaaacccgatgacaccaccatgtactactg cgccagagacagaagctacggcgacagcagctgggctctggatgcttggggccagg gcacaaccgtggtggtgtctgccgcctctacaaagggccccagcgtgttccctctggc ccctagcagcaagagcacatctggcggaacagccgccctgggctgcctcgtgaagg actactttcccgagcccgtgaccgtgtcctggaattctggcgccctgaccagcggcgtg cacacctttccagctgtgctgcagtccagcggcctgtacagcctgagcagcgtcgtga cagtgcccagcagctctctgggcacccagacctacatctgcaacgtgaaccacaagc ccagcaacaccaaggtggacaagaaggtggaacccaagagctgcgacaagaccca cacctgtcccccttgtcctgcccccgaactgctgggaggcccttccgtgttcctgttccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggt ggtggatgtgtcccacgaggaccctgaagtgaagttcaattggtacgtggacggcgtg gaagtgcacaacgccaagaccaagccaagagaaaaacagtacaacagcacctacc gggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtaca agtgcaaggtgtccaacaaggccctgcctgcccccatcgagaaaaccatcagcaagg ccaagggccagccccgcgaaccccaggtgtgcacactgcccccaagcagggacga gctgaccaagaaccaggtgtccctgagctgtgccgtgaaaggcttctacccctccgata tcgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccc cctgtgctgaacagcgacggctcattcttcctggtgtccaagctgacagtggacaagtc ccggtggcagcagggcaacgtgttcagctgctccgtgctgcacgaggccctgcacag ccactacacccagaagtccctgagcctgagccccggc LightchainA tacatccacgtaacccagaaccccagcagcctatccgtatccatcgacgacagagtg SEQID accatcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcac NO:245 aagcctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatgc cgtgcccagcagattttccggcagcggcttccacaccagcttccagagaccatcagc gatctgcaggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcaga ggcagcagactgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccac ctagcgacgagcagagaagtccggcacagcctctgtcgtgtgcctgagaacaactt ctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggc aacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctga gcagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgc gaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB gaggttagactggtggagtcaggaggggggcttgtgaagcccggtgggtctctccgc SEQID ctgagctgactgcctccggctttgatttcgataacgcctggatgacctgggtcaggcag NO:246 cctccaggtaagggactggagtgggtgggaagaatcacaggtccaggcgagggctg gtccgtgactacgcggaatctgttaaaggcggatacaatctcaaggpacaatacca agaataccttgtatttgaagatgaacaacgtaagaactgaagacaccaaatattacttct gtgccagaacaggcaaatactacgacttctggtccggctatccccctggcgaggaatat tttcaagactggggtcagggaacccagttatcgtgtcctccgacaaaacccatacccag gtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaaggt gtcctgcaaggcccctagcaacaccctgaaaacctacgacctgcactgggtgcgcag cgtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaag aaagtgatcgtggaacagttcaaggccaaaatgaccatcgactaagacagaagcacc aacaccgcctacctgagctgagcggcctgacctctggcgataccgccgtgtactact gcgccaagggcagcaagcaccggctgagagactacgccctgtacgacgatgacgg cgccctgaactgggccgtggatgtggactacctgagcaacctggaattctggggccag ggcacagccgtgaccgtgtcatctgataagacccacaccgcttccaccaagagcccat cggtcttccccctggcaccctcctccaagagcacctctgggggcacaacggccctgg gctgcctgatcaagaactacttccccaaaccaatgacggtgtcgtaaaactcaggcgc cctgaccagcggcatgcacaccttcccggagtcctacaatcctcaaaactctactccc tcagcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaa cgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgt gacaaaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtca gtcttcctcttccccccaaaacccaaggacaccctcatgatctcccggacccctgaggt cacatgcgtggtagtgaacatgagccacgaagaccctgaggtcaaattcaactggtat gttgacggcgtgaaggtgcataatgccaagacaaagccgcaggaggagcagtacaa cagcacgtaccgtgtggtcagcgtcctcaccgtcctgcaccaggactggctgaatggc aaggagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgagaaaacc atctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatgc cgggatgagctgaccaagaatcaagtcagcctgtggtgcctagtaaaaggcttctatcc cagcgacatcgccatggagtgagagagcaataggcagccggagaacaactacaag accacgcctcccgtgaggactccgacggctccttcacctctactcaaaactcaccgtg gacaagagcaggtggcagcaggggaacgtcttctcatgctccgtgctgcatgaggctc tgcacagccactacacgcagaagagcctctccctgtctccgggt LightchainB Gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgc SEQID cagcatcagctgcaagagcagccactccctgatccacggcgaccggaacaactacct NO:247 ggcttggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagc agcagagccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttc accctgaagatcaaccgggtagaaaccgaggacgtaggcacctactactgtatgcag ggcagagagagcccctggacctttagccaggacaccaagatggacatcaagaacaa aacccataccgcatccgaactgactcaggaccctgccgtctctgtggcactgaagcag actgtgactattacttgccgaggcgactcactgcggagccactacgcttcctggtatcag aagaaacccggccaggcacctgtgctgctgttctacggaaagaacaataggccatctg gcatccccgaccgcttttctggcagtgcatcagggaaccgagccagtctgaccattacc ggcgcccaggctgaggacgaagccgattactattgcagctcccgggataagagcgg ctccagactgagcgtgttcggaggaggaactaaactgaccgtcctcgataagacccat acccgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctga agtccggcacagcactgtcgtgtacctgagaacaacttctacccccgcgagaccaa agtgcagtggaaggtggacaacaccctgcagagcggcaacagccaggaaagcgtg accgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgag caaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcc tgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein32AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqyq SEQID avnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswaldawg NO:302 qgttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgv htfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcpp cpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvev hnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakg qprepqvytlppcqeemtknqvslwclvkgfypsdiavewesngqpennykttpp vldsdgsfflyskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv SEQID psrfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsdeq NO:303 lksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlsk adyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvqsgaevvkpgasvkvsckas ihwvrqapgqglewigs SEQID nyaqkfqgratltvdtsistaymelsrlrsddtavyyc NO:304 wgkgttvlvsssqvqlvesgggvvqpgrslrlscaas mhw vrqapgkqlewvaq yatyyadsvkgrftisrddskntlylqmmslr aedtavyy wgqgtlvtvssrtastkgpsvfplapcsrstses taalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssl gtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkp kdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfns tyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctl ppsqeemtknqvslscavkgfypsdiavewesngqpennykttppvldsd gsfflvskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckss lswylqkpgqspgsliy SEQID nrfsgvpdrfsgsgsgtdftlkisrveaedvgvyyc ftfgsgtkveikgqpk NO:305 aapdiqmtqspsslsasvgdrvtitcqas lnwyqqkpgkapklliykasnl htgvpsrfsgsgsgtdftltisslqpediatyyc fgqgtkleiktkpsrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqd skdstyslsstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein32NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgggt SEQID gtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcaggcc NO:306 cctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggcttccgggatagaatgaccctgacccaggacgtgtaccgcgagatcgcc tacatggacatccggggcctgaagcccgatgacaccgccatgtactactgcgccagaga cagaagctacggcgacagcagctgggctctggatgcttggggccagggcacaaccgtg gtggtgtctgccgcctctacaaagggcccctcggtgaccctctggccccttgcagcagaa gcaccagcgaatctacagccgccctgggctgcctcgtgaaggactacatcccgagcccg tgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgct ccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgg gcaccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaa gcgggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatactgggc ggaccctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacc cccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaat tggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagt tcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacg gcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaacc atcagcaaggccaagggccagccccgcgagcctcaagtgtataccagcccccttgcca ggaagagatgaccaagaaccaggtgtccagtagtgtacgtgaaaggcactaccccag cgacattaccgtggaatgggagagcaacggccagcccgagaacaactacaagaccacc ccccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaaga gccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaac cactacacccagaagtccctgtctctgtccctgggcaag LightchainA Tacatccacgtgacccaaagccccaacaacctgtccatgtccatcggcaacagaatgac SEQID catcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaagc NO:307 ctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcc cagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatctgcag gccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagagcagcagac tgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagc agctgaagtccggcacagcctctgtcgtgtgcctgctgattcaacttctacccccgcgagg ccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcg tgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgag caaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcag tctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:308 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagaccagggcagagccaccctgaccgtgaacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagaggtggaataggcggcggagtggtgcagcaggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccaggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctatacctgcagatgaacagcctacgggccgaggacaccacca tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgactgacaagcggcgtgcaca cctttccagccatgaccagagcagcagcctgtactactgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctataacatggaccacaaacccaacaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggctgtggaagtgcacaacgccaagaccaagcc cagagaagaacagttcaacagcacctaccaggtgatgtccatgctgaccatgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgaggacagcgacggctcattcttcctggtgtccaa gctgaccgtggacaagagccagtgacaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtactgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctaagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtacacaacaacaccaacacctacctgagct NO:309 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagatctccggcagcggctctggcaccgacttcaccctgaag atcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagta ccccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc cccgacatccagatgacccagagccccagcagcagtctgccagcgtgggcgacagag tgaccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcaga agcccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgt gcccagcagattttctgacaacggctccgacaccgacttcaccctgacaatcagctccctg cagcccgaggacattgccacctactactgccagcagaaccagacctacccctacaccttt ggccagggcaccaagaggaaatcaagaccaagggccccagccgtacggtggccgct cccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctagtc gtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaa cgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactc cacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaag gtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaac cggggcgagtgt BindingProtein33AminoAcidSequences HeavychainA Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikpqyga SEQID vnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdsswaldawgqg NO:310 ttvvvsaastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfp avlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpape flggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktk preeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqv ytlppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsff lyskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgfhtsfnltisdlqaddiatyycqlqffgrgsrlhikrtvaapsvfifppsdeqlks NO:311 gtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec HeavychainB Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwa SEQID gggtnynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysm NO:312 dywgqgttvtvsssqvqlvesgggvvqpgrslrlscaasgftftkawmhwvrq apgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqmmslraedt avyycrgvyyalspfdywgqgtlvtvssrtastkgpsvfplapcsrstsestaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktyt cnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmis rtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvlt vlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqeemt knqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskltv dksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspgsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikgqpkaa NO:313 pdivltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnv esgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleiktkgpsrt vaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqd skdstyslsstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein33NucleotideSequences HeavychainA agagcccacctggtgcagtctggcaccgccatgaagaaaccaggcgcctctgtgcgggt SEQID gtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcaggcc NO:314 cctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggcttccgggatagaatgaccctgacccaggacgtgtaccgcgagatcgcc tacatggacatccggggcctgaagcccgatgacaccgccatgtactactgcgccagaga cagaagctacggcgacagcagctgggctctggatgcttggggccagggcacaaccgtg gtggtgtctgccgcctctacaaagggcccctcggtgaccctctggccccttgcagcagaa gcaccagcgaatctacagccgccctgggctgcctcgtgaaggactacatcccgagcccg tgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgct ccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgg gcaccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaa gcgggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatactgggc ggaccctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacc cccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaat tggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagt tcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacg gcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaacc atcagcaaggccaagggccagccccgcgagcctcaagtgtataccagcccccttgcca ggaagagatgaccaagaaccaggtgtccagtagtgtacgtgaaaggcactaccccag cgacattaccgtggaatgggagagcaacggccagcccgagaacaactacaagaccacc ccccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaaga gccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaac cactacacccagaagtccctgtctctgtccctgggcaag LightchainA Tacatccacgtgacccaaagccccaacaacctgtccatgtccatcggcaacagaatgac SEQID catcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaagc NO:315 ctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcc cagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatctgcag gccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagagcagcagac tgcacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagc agctgaagtccggcacagcctctgtcgtgtgcctgctgattcaacttctacccccgcgagg ccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaagcg tgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactgag caaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcag tctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:316 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctgaagtccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatcctctcaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgcttcgaccaagggcccatcggtgttccctctggcc ccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacac ctttccagccatgctccagagcagcagcctgtactctctgagcaacgtcgtaacagtgccc agcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaaca ccaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagccc ctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctgat gatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccg aggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagccc agagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacca ggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagc tccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgtac cctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtgccgtga aaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgagaa caactacaagaccaccccccctgtgctggacagcgacggctcattcttcctggtgtccaag ctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgca cgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:317 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagattctccggcagcggctctggcaccgacttcaccctgaag atcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagta ccccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc cccgacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggc caccatcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtg gtatcagcagaagcccggccagccccccaagctgctgattttcgccgccagcaacgtgg aaagcggcgtgccagccagattttccggcagcggctctggcaccgacttcaccctgacca tcaaccccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggt gccctacacctttggccagggcaccaagctggaaatcaagaccaagggccccagccgta cggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtgga aggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggac agcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacg agaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgacc aagagcttcaaccggggcgagtgt BindingProtein34AminoAcidSequences HeavychainA Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwisheg SEQID dkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddga NO:318 lnwavdvdylsnlefwgqgtavtvssastkgpsvfplapcsrstsestaalgclvkdyfp epvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkv dkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpe vqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkgl pssiektiskakgqprepqvytlppcqeemtknqvslwclvkgfypsdiavewesng qpennykttppvldsdgsfflyskltvdksrwqegnvfscsvmhealhnhytqkslsls lgk LightchainA Dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassras SEQID gvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtvaapsv NO:319 fifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstys lsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvqsgaevvkpgasvkvsckas ihwvrqapgqglewigs SEQID nyaqkfqgratltvdtsistaymelsrlrsddtavyyc NO:320 wgkgttvlvsssqvqlvesgggvvqpgrslrlscaas mhwvrq apgkqlewvaq yatyyadsvkgrftisrddskntlylqmmslraedt avyyc wgqgtlvtvssrtastkgpsvfplapcsrstsestaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktyt cnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmis rtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvlt vlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqeemt knqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskltv dksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckss lswylqkpgqspgsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyyc ftfgsgtkveikgqpkaap NO:321 diqmtqspsslsasvgdrvtitcqasq lnwyqqkpgkapklliy nlhtgv psrfsgsgsgtdftltisslqpediatyyc fgqgtkleiktkpsrtvaapsvf ifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysl sstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein34NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaagg SEQID tgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcagc NO:322 gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaagaaa gtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcaccaacac cgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtactactgcgccaa gggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcgccctgaac tgggccgtggatgtggactacctgagcaacctggaattctggggccagggcacagccgt gaccgtgtcatctgcttcgaccaagggcccctcggtgttccctctgaccccttgcagcaga agcaccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagccc gtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtg ctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcct gggcaccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggac aagcgggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatttctgg gcggaccctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccgga cccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttca attggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaaca gttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaa cggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaa accatcagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttg ccaggaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccc cagcgacattgccgtggaatgggagagcaacggccagcccgagaacaactacaagacc accccccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggaca agagccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcac aaccactacacccagaagtccctgtctctgtccctgggcaag LightchainA gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccag SEQID catcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctggctt NO:323 ggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcaga gccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaa gatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagag agcccctggacctttggccagggcaccaaggtggacatcaagcgtacggtggccgctcc cagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtg tgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaacgc cctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccac ctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtg tacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccg gggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:324 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctaagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtacacaacaacaccaacacctacctgagct NO:325 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagatctccggcagcggctctggcaccgacttcaccctgaag atcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagta ccccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc cccgacatccagatgacccagagccccagcagcagtctgccagcgtgggcgacagag tgaccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcaga agcccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgt gcccagcagattttctgacaacggctccgacaccgacttcaccctgacaatcagctccctg cagcccgaggacattgccacctactactgccagcagaaccagacctacccctacaccttt ggccagggcaccaagaggaaatcaagaccaagggccccagccgtacggtggccgct cccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctagtc gtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaa cgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactc cacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaag gtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaac cggggcgagtgt BindingProtein35AminoAcidSequences HeavychainA Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwisheg SEQID dkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrdyalydddga NO:326 lnwavdvdylsnlefwgqgtavtvssastkgpsvfplapcsrstsestaalgclvkdyfp epvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkv dkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpe vqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkgl pssiektiskakgqprepqvytlppcqeemtknqvslwclvkgfypsdiavewesng qpennykttppvldsdgsfflyskltvdksrwqegnvfscsvmhealhnhytqkslsls lgk LightchainA Dfvltqsphslsvtpgesasiscksshslihgdrnnylawyvqkpgrspqlliylassras SEQID gvpdrfsgsgsdkdftlkisrvetedvgtyycmqgrespwtfgqgtkvdikrtvaapsv NO:327 fifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstys lsstltlskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwa SEQID gggtnynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysm NO:328 dywgqgttvtvsssqvqlvesgggvvqpgrslrlscaasgftftkawmhwvrq apgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqmmslraedt avyycrgvyyalspfdywgqgtlvtvssrtastkgpsvfplapcsrstsestaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktyt cnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmis rtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvlt vlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqeemt knqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskltv dksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspgsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikgqpkaa NO:329 pdivltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnv esgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleiktkgpsrt vaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqd skdstyslsstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein35NucleotideSequences HeavychainA caggtgcacctgacacagagcggacccgaagtgcggaagcctggcacctctgtgaagg SEQID tgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcactgggtgcgcagc NO:330 gtgccaggacagggactgcagtggatgggctggatcagccacgagggcgacaagaaa gtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacagaagcaccaacac cgcctacctgcagctgagcggcctgacctctggcgataccgccgtgtactactgcgccaa gggcagcaagcaccggctgagagactacgccctgtacgacgatgacggcgccctgaac tgggccgtggatgtggactacctgagcaacctggaattctggggccagggcacagccgt gaccgtgtcatctgcttcgaccaagggcccctcggtgttccctctgaccccttgcagcaga agcaccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagccc gtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtg ctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcct gggcaccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggac aagcgggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatttctgg gcggaccctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccgga cccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttca attggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaaca gttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaa cggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaa accatcagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttg ccaggaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccc cagcgacattgccgtggaatgggagagcaacggccagcccgagaacaactacaagacc accccccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggaca agagccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcac aaccactacacccagaagtccctgtctctgtccctgggcaag LightchainA gacttcgtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccag SEQID catcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctggctt NO:331 ggtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcaga gccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaa gatcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagag agcccctggacctttggccagggcaccaaggtggacatcaagcgtacggtggccgctcc cagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtg tgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaacgc cctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccac ctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaaggtg tacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccg gggcgagtgt HeavychainB caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:332 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctgaagtccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatcctctcaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgcttcgaccaagggcccatcggtgttccctctggcc ccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggacta ctttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacac ctttccagccatgctccagagcagcagcctgtactctctgagcaacgtcgtaacagtgccc agcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaaca ccaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagccc ctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctgat gatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccg aggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagccc agagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacca ggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagc tccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgtac cctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtgccgtga aaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgagaa caactacaagaccaccccccctgtgctggacagcgacggctcattcttcctggtgtccaag ctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgca cgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:333 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagattctccggcagcggctctggcaccgacttcaccctgaag atcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagta ccccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc cccgacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggc caccatcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtg gtatcagcagaagcccggccagccccccaagctgctgattttcgccgccagcaacgtgg aaagcggcgtgccagccagattttccggcagcggctctggcaccgacttcaccctgacca tcaaccccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggt gccctacacctttggccagggcaccaagctggaaatcaagaccaagggccccagccgta cggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggca cagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtgga aggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggac agcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacg agaagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgacc aagagcttcaaccggggcgagtgt BindingProtein36AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkprg SEQID gavnyarplqgrvtmtrdvysdtaflelrsltvddtavyftrgkncdynwdfehwgrg NO:334 tpvivssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfp avlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpape flggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktk preeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqv ytlppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsff lyskltvdksrwqegnvfscsvmheallnhytqkslslslgk LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfsg SEQID srwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsdeql NO:335 ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskad yekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvqsgaevvkpgasvkvsckas ihwvrqapgqglewigs SEQID nyaqkfqgratltvdtsistaymelsrlrsddtavyyc NO:336 wgkgttvlvsssqvqlvesgggvvqpgrslrlscaas mhwvrq apgkqlewvaq yatyyadsvkgrftisrddskntlylqmmslraedt avyyc wgqgtlvtvssrtastkgpsvfplapcsrstsestaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktyt cnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmis rtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvlt vlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqeemt knqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskltv dksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckss lswylqkpgqspgsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyyc ftfgsgtkveikgqpkaap NO:337 diqmtqspsslsasvgdrvtitcqas lnwyqqkpgkapklliykasnlhtgv psrfsgsgsgtdftltisslqpediatyyc gqgtkleiktkpsrtvaapsvf ifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstysl sstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein36NucleotideSequences HeavychainA caggtacagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcgga SEQID tcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcagactgg NO:338 cccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagccgtgaa ctacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacagcgataccg ccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttctgcacccggg gcaagaactgcgactacaactgggacttcgagcactggggcagaggcacccctgtgatc gtgtcaagcgcgtcgaccaagagcccctcggtgttccctctggccccttgcagcagaagc accagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtg accgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcc agagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggc accaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagc gggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatttagggcgg accctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacccc cgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattg gtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttc aacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacgg caaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaacca tcagcaaggccaagggccagccccgcgagcctcaagtgtgtaccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccc cccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccctgggcaag LightchainA Gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagccat SEQID catcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcctgga NO:339 caggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccccgata gattcagcggctccagatggggccctgactacaacctgaccatcagcaacctggaaagc ggcgacttcggcatgtactactgccagcagtacgagttcttcggccagggcaccaaggtg caggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctagcgac gagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgc gaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaa agcgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacac tgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccaggg cctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:340 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctaagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtacacaacaacaccaacacctacctgagct NO:341 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagatctccggcagcggctctggcaccgacttcaccctgaag atcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagta ccccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc cccgacatccagatgacccagagccccagcagcagtctgccagcgtgggcgacagag tgaccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcaga agcccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgt gcccagcagattttctgacaacggctccgacaccgacttcaccctgacaatcagctccctg cagcccgaggacattgccacctactactgccagcagaaccagacctacccctacaccttt ggccagggcaccaagaggaaatcaagaccaagggccccagccgtacggtggccgct cccagcgtgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctagtc gtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtggaaggtggacaa cgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactc cacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaagcacaag gtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaac cggggcgagtgt BindingProtein37AminoAcidSequences HeavychainA Qvqlvqsggqmkkpgesmriscrasgyefidctlnwirlapgkrpewmgwlkprg SEQID gavnyarplqgrvtmtrdvysdtaflelrsltvddtavyftrgkncdynwdfehwgrg NO:342 tpvivssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfp avlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpape flggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktk preeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqv ytlppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsff lyskltvdksrwqegnvfscsvmheallnhytqkslslslgk LightchainA Eivltqspgtlslspgetaiiscrtsqygslawyqqrpgqaprlviysgstraagipdrfsg SEQID srwgpdynltisnlesgdfgvyycqqyeffgqgtkvqvdikrtvaapsvfifppsdeql NO:343 ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskad yekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwa SEQID gggtnynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysm NO:344 dywgqgttvtvsssqvqlvesgggvvqpgrslrlscaasgftftkawmhwvrq apgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqmmslraedt avyycrgvyyalspfdywgqgtlvtvssrtastkgpsvfplapcsrstsestaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktyt cnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmis rtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvlt vlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqeemt knqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskltv dksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspgsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikgqpkaa NO:345 pdivltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnv esgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleiktkgpsrt vaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqd skdstyslsstltlskadyekhkvyacevthqglsspvtksfngec BindingProtein37NucleotideSequences HeavychainA caggtacagctggtgcagtctggcggccagatgaagaaacccggcgagagcatgcgga SEQID tcagctgcagagccagcggctacgagttcatcgactgcaccctgaactggatcagactgg NO:346 cccctggcaagcggcctgagtggatgggatggctgaagcctagaggcggagccgtgaa ctacgccagacctctgcagggcagagtgaccatgacccgggacgtgtacagcgataccg ccttcctggaactgcggagcctgaccgtggatgataccgccgtgtacttctgcacccggg gcaagaactgcgactacaactgggacttcgagcactggggcagaggcacccctgtgatc gtgtcaagcgcgtcgaccaagagcccctcggtgttccctctggccccttgcagcagaagc accagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtg accgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcc agagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggc accaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagc gggtggaatctaagtacggccctccctgccctccttgcccagcccctgaatttagggcgg accctccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacccc cgaagtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattg gtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttc aacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacgg caaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaacca tcagcaaggccaagggccagccccgcgagcctcaagtgtgtaccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccc cccctgtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccctgggcaag LightchainA Gagatcgtgctgacacagagccctggcaccctgagcctgtctccaggcgagacagccat SEQID catcagctgccggacaagccagtacggcagcctggcctggtatcagcagaggcctggac NO:347 aggcccccagactcgtgatctacagcggcagcacaagagccgccggaatccccgatag attcagcggctccagatggggccctgactacaacctgaccatcagcaacctggaaagcg gcgacttcggcgtgtactactgccagcagtacgagttcttcggccagggcaccaaggtgc aggtggacatcaagcgtacggtggccgctcccagcgtgttcatcttcccacctagcgacg agcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcga ggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccaggaaag cgtgaccgagcaggacagcaaggactccacctacagcctgagcagcaccctgacactg agcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcc tgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagagcagaatctggccctggcctcgtgaagcctaccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagcc NO:348 acctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaactaca accccagcctgaagtccagaaagaccatcagcaaggacaccagcaagaaccaggtgtc cctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagagaca agggctacagctactactacagcatgaactactggagccaggacaccaccgtgaccgtg tcatcctctcaggtgcagctggtagaatctggcggcggagtggtgcagcctggcagaagc ctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctagatacactaggtg cgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaac agctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggacg acagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccgt gtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaacc ctcgtgaccgtatctaatcagaccgcttcgaccaagagcccatcagtgttccctaggccc cttgcagcagaagcaccagcgaatctacagccaccctgaactgcctcatgaaggactact ttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctt tccagccgtgctccagagcagcggcctgtactctagagcagcgtcgtgacagtgcccag cagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaacacc aaggtggacaagcgggtggaatctaagtacggccaccctgccaccttgcccagcccct gaatttctgagcggaccctccgtgttcctgttccccccaaaacccaaggacaccctgatga tcagccggacccccgaagtgacctgcgtggtaatggatgtgtcccaggaagatcccgag gtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccag agaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcaccagg actggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccagacc atcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgtaccct gccccctagccaggaagagatgaccaagaaccaggtgtccctgagagtgccgtgaaag gcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgagaacaa ctacaagaccaccccccctgtgctggacagcgacggctcattcttcctggtgtccaagctg accgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacga ggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:349 ggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagat tcagcggcgtgcccgacagattaccggcagcggctaggcaccgacttcaccagaaga tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcaccatggcagcggcaccaaggtagaaatcaagggccagcccaaggccgcccc cgacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggcca ccatcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtggt atcagcagaagcccggccagccccccaagctgctgaattcgccgccagcaacgtggaa agcggcgtgccagccagattttccggcagcggctctggcaccgacttcaccctgaccatc aaccccgtggaagccaacgacgtggccaactactactgccagcagagccggaagatgc cctacacctttggccagggcaccaagctggaaatcaagaccaagggccccagccgtacg gtggccgctcccagcgtgacatcttcccacctagcgacgagcagctgaagtccggcaca gcctctgtcgtgtgcctgctgaacaacttctacceccgcgaggccaaagtgcagtggaag gtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagc aaggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacgaga agcacaaggtgtacgcctgcgaagtgacccaccagggcctatctagccccgtgaccaag agcttcaaccggggcgagtgt BindingProtein38AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:350 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:351 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikp SEQID qygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdssw NO:352 aldawgqgttvvvsasqvqlvesgggvvqpgrslrlscaasgftftkawmhw vrqapgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqmnslra edtavyycrgvyyalspfdywgqgtlvtvssrtastkgpsvfplapcsrstsesta algclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtk tytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtl misrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvv svltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsqee mtknqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvskl tvdkstwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divimtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikgqpkaa NO:353 pyilwtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgv psrfsgsathtsfnltisdlqaddiatyycqvlqffgrgsrlhiktkgpsrtvaapsvfifpp sdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstlt lskadyekhkvyacevthqglsspvtksfnrgec BindingProtein38NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactaggtacgccaggc NO:354 ccctggacaggaactggaatgaatcggcagcatctaccccggcaacgtaaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgactactgcacccggt cccactacggcaggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgaccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtccggaactctggcgctctgacaagcagcgtgcacaccatccagccgtgaccagag cagcggcctgtactactgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcgggt ggaatctaagtacggccctccagccctccttgcccagcccagaatactgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccagatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacgacgtagaagtgcacaacgccaagaccaaacccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccagccaggaaga gatgaccaagaaccaggtgtccagtggtgtacgtgaaaggcttctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattatcctatactccaagctgaccgtgaacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctaggcaag LightchainA Gacatccagatgacccagagccccagcagcctgtctgccagcgtggacgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcagaagc NO:355 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagctccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacctttggc cagggcaccaagctggaaatcaagcgtacggtagccactcccaacgtattcatatccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttct acccccgcgaggccaaggtgcagtggaaggtggacaatgccctgcagagcggcaaca gccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgagcagca ccctgaccagagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgac ccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB agagcccacctggtgcagtaggcaccgccatgaagaaaccaggcgcctctgtgcgggt SEQID gtcctgtcagacaagcggctacaccttcaccgcccacatcctgttctggttccggcaggcc NO:356 cctggcagaggactggaatgggtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggatccgggatagatttgacccttacccgggacgtgtaccgcgagatcgcct acatggacatccggggcctgaagcccgatgacaccgccgtgtactactgcgccagagac agaagctacggcgacagcaactaggactagatgatgggaccagggcacaaccatgg tggtgtctgcctctcaggtgcagctggtggaatctggcggcggagtggtgcagcctggca gaagcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcact gggtgcgccaggcccctggaaagcagaggaatgggtggcccagatcaaggacaaga gcaacagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgg gacgacagcaagaacaccctatacctgcagatgaacagcctgcgggccgaggacacca ccgtgtactactgtcggggcgtatactatgccctgagcccatcgattactagggccaggg aaccctcgtgaccgtgtctagtcggaccgcacgaccaagggcccatcggtgttccctctg gccccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaagga ctactttcccgagcccgtgaccgtgtcaggaaactggcgctctgacaagcggcgtgcac acctttccagccgtgaccagagcagcggcctgtactactgagcagcgtcgtgacagtgc ccagcagcagcctggacaccaagacctacacctgtaacgtgaaccacaagcccagcaa caccaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagc ccctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctg atgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgagaccgtgagcacc aggactggctgaacaacaaagagtacaagtgcaaagtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgaggacagcgacggctcattcttcctggtgtccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgaccgtgatgc acgaggccagcacaaccactacacccagaagtccagtactgtccagggcaag LightchainB Gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgcca SEQID gcatcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgag NO:357 ctggtatctacagaaacccggccagagcccccagtccagatctacaaggtgtccaacag attcagcggcgtgcccgacagattaccggcagcggctaggcaccgacttcaccctgaa gatcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagt accccttcacctttggcagcggcaccaaggtggaaatcaagggccagcccaaggccgcc ccctacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagt gaccatcaactgccagacctctacagggcgtgggcagcgacctgcactggtatcagcaca agcctggcagaacccccaagagagatccaccacacaagcagcatggaagatggcgt gcccagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatctg caggccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggcagca gactgcacatcaagaccaagggccccagccgtacggtggccgctcccagcgtgttcatct tcccacctagcgacgagcagctgaagtccggcacagcactgtcgtgtgcctgctgaaca acttctacccccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcgg caacagccaggaaagcgtgaccgagcaggacagcaaggactccacctacagcctgag cagcaccctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaa gtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein39AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:358 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:359 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikp SEQID qygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdssw NO:360 aldawgqgttvvvsadkthtqvqlvesgggvvqpgrslrlscaasgftftkaw mhwvrqapgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqm nslraedtavyycrgvyyalspfdywgqgtlvtvssdkthtastkgpsvfplapc srstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvt vpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfp pkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeq fnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvc tlppsqeemtknqvslscavkgfypsdiavewesngqpennykttppyldsd gsfflvskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikdkthtyih NO:361 vtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvpsrfs gsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtrtvaapsvfifppsdeql ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskad yekhkvyacevthqglsspvtksfnrgec BindingProtein39NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactaggtacgccaggc NO:362 ccctggacaggaactggaatgaatcggcagcatctaccccggcaacgtaaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgactactgcacccggt cccactacggcaggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgaccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtccggaactctggcgctctgacaagcagcgtgcacaccatccagccgtgaccagag cagcggcctgtactactgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcgggt ggaatctaagtacggccctccagccctccttgcccagcccagaatactgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccagatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacgacgtagaagtgcacaacgccaagaccaaacccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccagccaggaaga gatgaccaagaaccaggtgtccagtggtgtacgtgaaaggcttctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattatcctatactccaagctgaccgtgaacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctaggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:363 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB agagcccacctggtgcagtctggcaccgccatgaagaaaccaagcgcctctgtgcgggt SEQID gtcctgtcagacaagcagctacaccttcaccgcccacatcctgttctggttccggcagacc NO:364 cctggcagaggactggaatgagtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgagatcacct acatggacatccggggcctgaagcccgatgacaccgccgtggggctactgcgccagagac agaagctacggcgacagcagagggctctggatgcttggggccagggcacaaccgtgg tggtgtctgccgacaaaacccatacccaagtgcaactaatggaatctagcgacggagtg gtgcagcctgacaaaaacctgaaactgaactatgccgccagcgacttcaccttcaccaa ggcctggatgcactgggtgcgccaggcccctggaaagcagaggaatgggtggcccag atcaaggacaagagcaacagctacgccacctactacgccgacagcgtgaagggccagtt caccatcagccgggacgacagcaagaacaccagtacctgcagatgaacagcctgcag gccgagaacaccgccgtatactactgtcggggcgtgtactatgccctgaaccccttgatt actggggccaaagaaccctcgtaaccgtatctaatgataagacccacaccgcttcgacca agggcccatcggtgttccctctgacccatgcagcagaagcaccagcgaatctacagccg ccctgggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctggaactctgg cgctctgacaagcggcgtgcacacctttccagccgtgctccagagcagcgacctgtactc tctgagcagcgtcgtgacagtgcccagcagcagcctgagcaccaaaacctacacctgta acgtggaccacaagcccagcaacaccaagatggacaagcgggtggaatctaagtacga ccctccctgccctccttgcccagcccctgaatactgagcgaaccctccgtgttcctattccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtg gtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtgg tgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgcaag gtgtccaacaagggcctgcccagctccatcgagaaaaccatcagcaaggccaagggcc agccccgcgagcctcaagtgtgtaccctgccccctagccagaaaaagatgaccaagaac caggtgtccctaagctgtgccgtgaaaggcttctaccccagcaacattgccgtaaaatgg gagagcaacggccagcccgagaacaactacaagaccaccccccctgtgctggacagcg acggctcattcttcctggtgtccaagctgaccgtggacaagagccggtggcaggaaggca acgtattcagctgctccgtgatgcacgaggccctgcacaaccactacacccagaagtccc tgtctctgtccctagacaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:365 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgigtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein40AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:366 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:367 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwvrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlylqmnslraedtavvycrgvyyal NO:368 spfdywgqgtlvtvsssrahlvqsgtamkkpgasvrvscqtsgytftahilfwfr qapgrglewvgwikpqygavnfgggfrdrvtltrdvyreiaymdirglkpddt avyycardrsygdsswaldawgqgttvvvsartastkgpsvfplapcsrstsest aalgclvkdyfpepvtvswnsgaltsgvhtfpaviqssglysissvvtvpssslgt ktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtl misrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrv vsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsq eemtknqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvs kltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgthtsfnltisdlqaddiatyycqvlqffgrgsrlhikgqpkaapdivmtqtplsl NO:369 svtpgqpasiscksaqslvhnnantylswylqkpggspqsliykvsnrfsgvpdrfsgs gsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveiktkgpsrtvaapsvfifpps deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec BindingProtein40NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactaggtacgccaggc NO:370 ccctggacaggaactggaatgaatcggcagcatctaccccggcaacgtaaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgactactgcacccggt cccactacggcaggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgaccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtccggaactctggcgctctgacaagcagcgtgcacaccatccagccgtgaccagag cagcggcctgtactactgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcgggt ggaatctaagtacggccctccagccctccttgcccagcccagaatactgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccagatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacgacgtagaagtgcacaacgccaagaccaaacccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccagccaggaaga gatgaccaagaaccaggtgtccagtggtgtacgtgaaaggcttctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattatcctatactccaagctgaccgtgaacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctaggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:371 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:372 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcsacaga SEQID gtgaccatcaactgccagacctctcaggctgggcagegacctgcactggtatc NO:373 agcacaagcctggcagagcceccaagagctgatccaccacacaagcagcgtg gaagatggcgtgcccagcagattaccggcagcggcttccacaccagcttcaacc tgaccatcagcgatagcaggccgacgacattgccacctactattgtcaggtgctg cagttcttcggcagaggcagcagactgcacatcaagggccagcccaaggccgc ccccgacatcgtgatgacccaacccccagagcctgagcgtgacacctggaca gcctgccagcatcagctgcaagagcagccagagcctggtgcacaacaacgcca acacctacctgagctggtatctgcagaagcccggccagagcccccagtccctgat ctacaaggtgtccaacagattcagcgcgtgcccgacagattctccggcagcgg ctctggcaccgacttcaccctgaagatcagccgggtggaagccgaggacgtggg cgtgtactattgtggccagggcacccagtaccccttcacattggcagcggcacca aggtggaaatcaagaccaagggccccagccgtacggtggccgctcccagcgtg ttcatcttcccacctagcgacgagcagctgaagtccggcacagcactgtcgtgtg cctgctgaaacttctacccccgcgaggccaaagtgcagtggaaggtggacaa cgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaag gactccacctacagcctgagcagcaccctgacactgacaaggccgactacga aagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtg accaagagcttcaaccggggcgagtgt BindingProtein41AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:374 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:375 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwvrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlylqmnslraedtavvycrgvyyal NO:376 spfdywgqgtlvtvsssrahlvqsgtamkkpgasvrvscqtsgytftahilfwfr qapgrglewvgwikpqygavnfgggfrdrvtltrdvyreiaymdirglkpddt avyycardrsygdsswaldawgqgttvvvsartastkgpsvfplapcsrstsest aalgclvkdyfpepvtvswnsgaltsgvhtfpaviqssglysissvvtvpssslgt ktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtl misrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrv vsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsq eemtknqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvs kltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgthtsfnltisdlqaddiatyycqvlqffgrgsrlhikgqpkaapdivmtqtplsl NO:377 svtpgqpasiscksaqslvhnnantylswylqkpggspqsliykvsnrfsgvpdrfsgs gsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveiktkgpsrtvaapsvfifpps deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec BindingProtein41NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactaggtacgccaggc NO:378 ccctggacaggaactggaatgaatcggcagcatctaccccggcaacgtaaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgactactgcacccggt cccactacggcaggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgaccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtccggaactctggcgctctgacaagcagcgtgcacaccatccagccgtgaccagag cagcggcctgtactactgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcgggt ggaatctaagtacggccctccagccctccttgcccagcccagaatactgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccagatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacgacgtagaagtgcacaacgccaagaccaaacccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccagccaggaaga gatgaccaagaaccaggtgtccagtggtgtacgtgaaaggcttctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattatcctatactccaagctgaccgtgaacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctaggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:379 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB caggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaagcctgagact SEQID gagctgtgccgccaacggatcaccttcaccaaggcctggatgcactgggtacgccagg NO:380 cccctggaaagcagaggaatgggtggcccagatcaaggacaagagcaacagctacgc cacctactacgccgacagcgtgaagggccggttcaccatcagccgggacgacagcaag aacaccctgtacctgcagatgaacagcctgcgggccgaggacaccaccatgtactactgt cggggcgtgtactatgccagagccccttcgattactggggccagggaaccctcgtgacc gtgtctagtgacaaaacccataccaaagcccacctagtgcagtctggcaccgccatgaag aaaccaggcgcctctgtacggatgtcctgtcagacaagcggctacaccttcaccgcccac atcctgttctggttccggcaggcccctaacaaaggactggaatgagtggaataaatcaag ccccagtatggcgccgtgaacttcggcggaaacttccgggataaagtgaccctgacccg ggacgtgtaccgcgagatcgcctacatggacatccggggcctgaagcccgatgacaccg ccgtgtactactgcgccagagacagaagctacggcgacagcagctgggctctggatgctt ggggccagggcacaaccgtggtggtgtctgccgataagacccacaccaccagcacaaa gggcccatcggttccctctggccccagcagcagaagcaccagcgaatctacagccgc cctgggctgcctcgtgaagaactacatcccaagcccatgaccatgtcctggaactaggc gctctgacaaacggcgtacacacctttccagccgtactccagaacaacggcctgtactct ctgagcagcgtcgtgacagtgcccagcagcagcctgggcaccaagacctacacctgtaa cgtggaccacaagcccagcaacaccaaggtggacaagcgggtggaatctaagtacggc cctccctgccctccttgcccagcccctgaatactgggcggaccctccgtgacctgttcccc ccaaagcccaaggacaccctgatgatcagccgaacccccgaagtgacctgcatggtggt ggatgtgtcccaggaagatcccgaggtacagttcaattggtacatggacggcgtgaaagt gcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtggtg tccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgcaaggt gtccaacaagggcctgcccagctccatcgagaaaaccatcagcaaggccaagggccag ccccgcgagcctcaagtgtgtaccctgccccctagccaggaagaaataaccaagaacca ggtgtccctgagagtgccgtaaaaggatctaccccagcgacattgccgtggaatggga gagcaacggccaaccegaaaacaactacaaaaccaccccccctgtgaggacagegac ggctcattcttcctggtgtccaagctgaccgtggacaagagccggtggcaggaaggcaac gtgttcagctgaccgtgatgcacgaggccctgcacaaccactacacccagaagtccctgt ctctgtccctgggcaag LightchainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtgac SEQID catcaactgccagacctctcagggcgtgggcagcgacctgcactggtatcagcacaagc NO:381 ctggcagagcccccaaactactgatccaccacacaagcagcgtggaagatggcgtgcc cagcagattttccggcagcggcttccacaccagcttcaacctgaccatcagcgatctgcag gccgacgacattgccacctactattgtcaggtgctgcagttcttcggcagaggcagcagac tgcacatcaaggacaaaaacccataccgacatcgtgatgacccagacccccctgagcctga gcgtgacacctggacagcctgccagcatcagctgcaagagcagccagagcctggtgca caacaacgccaacacctacctgaactagtatagcagaagcccagccagagcccccagt ccctgatctacaaggtgtccaacagattcagcggcgtgcccgacagattctccggcagcg gctctggcaccgacttcaccctgaagatcagccgggtggaagccgaggacgtgggcgtg tactattgtggccagggcacccagtaccccttcacctttggcagcggcaccaaggtggaa atcaaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccaccta gcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgagaacaacttctacc cccgcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagcc aggaaagcatgaccgagcaggacagcaaggactccacctacagcctgagcagcaccct gacactgagcaaggccgactacgagaagcacaagatgtacacctgcaaaatgacccac cagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein42AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:382 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:383 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikp SEQID qygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdssw NO:384 aldawgqgttvvvsadkthtqvqlvesgggvvqpgrslrlscaasgftftkaw mhwvrqapgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqm nslraedtavyycrgvyyalspfdywgqgtlvtvssdkthtastkgpsvfplapc srstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvt vpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfp pkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeq fnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvc tlppsqeemtknqvslscavkgfypsdiavewesngqpennykttppyldsd gsfflvskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikdkthtyih NO:385 vtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvpsrfs gsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtrtvaapsvfifppsdeql ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskad yekhkvyacevthqglsspvtksfnrgec BindingProtein42NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:386 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:387 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB agagcccacctggtgcagtctggcaccgccatgaagaaaccaagcgcctctgtgcgggt SEQID gtcctgtcagacaagcagctacaccttcaccgcccacatcctgttctggttccggcagacc NO:388 cctggcagaggactggaatgagtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgagatcacct acatggacatccggggcctgaagcccgatgacaccgccgtggggctactgcgccagagac agaagctacggcgacagcagagggctctggatgcttggggccagggcacaaccgtgg tggtgtctgccgacaaaacccatacccaagtgcaactaatggaatctagcgacggagtg gtgcagcctgacaaaaacctgaaactgaactatgccgccagcgacttcaccttcaccaa ggcctggatgcactgggtgcgccaggcccctggaaagcagaggaatgggtggcccag atcaaggacaagagcaacagctacgccacctactacgccgacagcgtgaagggccagtt caccatcagccgggacgacagcaagaacaccagtacctgcagatgaacagcctgcag gccgagaacaccgccgtatactactgtcggggcgtgtactatgccctgaaccccttgatt actggggccaaagaaccctcgtaaccgtatctaatgataagacccacaccgcttcgacca agggcccatcggtgttccctctgacccatgcagcagaagcaccagcgaatctacagccg ccctgggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctggaactctgg cgctctgacaagcggcgtgcacacctttccagccgtgctccagagcagcgacctgtactc tctgagcagcgtcgtgacagtgcccagcagcagcctgagcaccaaaacctacacctgta acgtggaccacaagcccagcaacaccaagatggacaagcgggtggaatctaagtacga ccctccctgccctccttgcccagcccctgaatactgagcgaaccctccgtgttcctattccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtg gtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtgg tgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgcaag gtgtccaacaagggcctgcccagctccatcgagaaaaccatcagcaaggccaagggcc agccccgcgagcctcaagtgtgtaccctgccccctagccagaaaaagatgaccaagaac caggtgtccctaagctgtgccgtgaaaggcttctaccccagcaacattgccgtaaaatgg gagagcaacggccagcccgagaacaactacaagaccaccccccctgtgctggacagcg acggctcattcttcctggtgtccaagctgaccgtggacaagagccggtggcaggaaggca acgtattcagctgctccgtgatgcacgaggccctgcacaaccactacacccagaagtccc tgtctctgtccctagacaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:389 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgigtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein43AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:390 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:391 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Rahlvqsgtamkkpgasvrvscqtsgytftahilfwfrqapgrglewvgwikp SEQID qygavnfgggfrdrvtltrdvyreiaymdirglkpddtavyycardrsygdssw NO:392 aldawgqgttvvvsadkthtqvqlvesgggvvqpgrslrlscaasgftftkaw mhwvrqapgkqlewvaqikdksnsyatyyadsvkgrftisrddskntlylqm nslraedtavyycrgvyyalspfdywgqgtlvtvssdkthtastkgpsvfplapc srstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvt vpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfp pkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeq fnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvc tlppsqeemtknqvslscavkgfypsdiavewesngqpennykttppyldsd gsfflvskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgqspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikdkthtyih NO:393 vtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvpsrfs gsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtrtvaapsvfifppsdeql ksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskad yekhkvyacevthqglsspvtksfnrgec BindingProtein43NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:394 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:395 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB agagcccacctggtgcagtctggcaccgccatgaagaaaccaagcgcctctgtgcgggt SEQID gtcctgtcagacaagcagctacaccttcaccgcccacatcctgttctggttccggcagacc NO:396 cctggcagaggactggaatgagtgggatggatcaagccccagtatggcgccgtgaactt cggcggaggcttccgggatagagtgaccctgacccgggacgtgtaccgcgagatcacct acatggacatccggggcctgaagcccgatgacaccgccgtggggctactgcgccagagac agaagctacggcgacagcagagggctctggatgcttggggccagggcacaaccgtgg tggtgtctgccgacaaaacccatacccaagtgcaactaatggaatctagcgacggagtg gtgcagcctgacaaaaacctgaaactgaactatgccgccagcgacttcaccttcaccaa ggcctggatgcactgggtgcgccaggcccctggaaagcagaggaatgggtggcccag atcaaggacaagagcaacagctacgccacctactacgccgacagcgtgaagggccagtt caccatcagccgggacgacagcaagaacaccagtacctgcagatgaacagcctgcag gccgagaacaccgccgtatactactgtcggggcgtgtactatgccctgaaccccttgatt actggggccaaagaaccctcgtaaccgtatctaatgataagacccacaccgcttcgacca agggcccatcggtgttccctctgacccatgcagcagaagcaccagcgaatctacagccg ccctgggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctggaactctgg cgctctgacaagcggcgtgcacacctttccagccgtgctccagagcagcgacctgtactc tctgagcagcgtcgtgacagtgcccagcagcagcctgagcaccaaaacctacacctgta acgtggaccacaagcccagcaacaccaagatggacaagcgggtggaatctaagtacga ccctccctgccctccttgcccagcccctgaatactgagcgaaccctccgtgttcctattccc cccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtggtg gtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacgtggacggcgtggaa gtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtgg tgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaagagtacaagtgcaag gtgtccaacaagggcctgcccagctccatcgagaaaaccatcagcaaggccaagggcc agccccgcgagcctcaagtgtgtaccctgccccctagccagaaaaagatgaccaagaac caggtgtccctaagctgtgccgtgaaaggcttctaccccagcaacattgccgtaaaatgg gagagcaacggccagcccgagaacaactacaagaccaccccccctgtgctggacagcg acggctcattcttcctggtgtccaagctgaccgtggacaagagccggtggcaggaaggca acgtattcagctgctccgtgatgcacgaggccctgcacaaccactacacccagaagtccc tgtctctgtccctagacaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:397 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein44AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:398 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:399 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwvrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlylqmnslraedtavvycrgvyyal NO:400 spfdywgqgtlvtvsssrahlvqsgtamkkpgasvrvscqtsgytftahilfwfr qapgrglewvgwikpqygavnfgggfrdrvtltrdvyreiaymdirglkpddt avyycardrsygdsswaldawgqgttvvvsartastkgpsvfplapcsrstsest aalgclvkdyfpepvtvswnsgaltsgvhtfpaviqssglysissvvtvpssslgt ktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtl misrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrv vsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvctlppsq eemtknqvslscavkgfypsdiavewesngqpennykttppvldsdgsfflvs kltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgthtsfnltisdlqaddiatyycqvlqffgrgsrlhikgqpkaapdivmtqtplsl NO:401 svtpgqpasiscksaqslvhnnantylswylqkpggspqsliykvsnrfsgvpdrfsgs gsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveiktkgpsrtvaapsvfifpps deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec BindingProtein44NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:402 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:403 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:404 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB tacatccacgtgacccagagccccagcagcctgtccgtgtccatcggcsacaga SEQID gtgaccatcaactgccagacctctcaggctgggcagegacctgcactggtatc NO:405 agcacaagcctggcagagcceccaagagctgatccaccacacaagcagcgtg gaagatggcgtgcccagcagattaccggcagcggcttccacaccagcttcaacc tgaccatcagcgatagcaggccgacgacattgccacctactattgtcaggtgctg cagttcttcggcagaggcagcagactgcacatcaagggccagcccaaggccgc ccccgacatcgtgatgacccaacccccagagcctgagcgtgacacctggaca gcctgccagcatcagctgcaagagcagccagagcctggtgcacaacaacgcca acacctacctgagctggtatctgcagaagcccggccagagcccccagtccctgat ctacaaggtgtccaacagattcagcgcgtgcccgacagattctccggcagcgg ctctggcaccgacttcaccctgaagatcagccgggtggaagccgaggacgtggg cgtgtactattgtggccagggcacccagtaccccttcacattggcagcggcacca aggtggaaatcaagaccaagggccccagccgtacggtggccgctcccagcgtg ttcatcttcccacctagcgacgagcagctgaagtccggcacagcactgtcgtgtg cctgctgaaacttctacccccgcgaggccaaagtgcagtggaaggtggacaa cgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaag gactccacctacagcctgagcagcaccctgacactgacaaggccgactacga aagcacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtg accaagagcttcaaccggggcgagtgt BindingProtein45AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:406 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:407 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB qvqlvesgggvvqpgrslrlscaasgftftkawmhwvrqapgkqlewvaqik SEQID dksnsyatyyadsvkgrftisrddskntlylqmnslraedtavyycrgvyyals NO:408 pfdywgqgtlvtvssdkthtrahlvqsgtamkkpgasvrvscqtsgytftahilf wfrqapgrglewvgwikpqygavnfgggfrdrvtltrdvyreiaymdirglkp ddtavyycardrsygdsswaldawgggttvvvsadkthtastkgpsvfplapc srstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgtyslssvvt vpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflf ppkpkdtimisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpree qfnstyrvvsvltvlhqdwllgkeykckvsnkglpssiektiskakgqprepq vctlppsqeemtknqvslscavkgfypsdiavewesngqpennykttppvld sdgsfflvskltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainB Yihvtqspsslsvsigdrvtincqtsqgvgsdlhwyqhkpgrapkllihhtssvedgvp SEQID srfsgsgfhtsfnltisdlqaddiatyycqvlqffgrgsrlhikdkthtdivmtqtpl NO:409 slsvtpgqpasisckssqslvhnnantylswylqkpgqspqsliykvsnrfsgvpdrf sgsgsgtdftlkisrveaedvgvyycgqgtqypftfgsgtkveikdkthtrtvaaps vfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec BindingProtein45NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:410 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggccac SEQID catcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtggta NO:411 tcagcagaagcccggccaaccccccaagctgctgattttcgccgccaacaacatggaaa gcggcgtgccagccagattttccgacagcggctctggcaccgacttcaccctgaccatca accccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggtacc ctacacctttggccagggcaccaagctggaaatcaagcgtacggtggccgctcccagcg tgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcct gctgaacaacttctacccccgcgaggccaaggtgcagtggaaggtggacaatgccctgc agagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctaca gcctgagcagcaccagaccctgagcaaggccaactacgagaaacacaaggtatacgc ctgcgaagtaacccaccaggacctgtctagccccgtgaccaagagcttcaaccgggacg agtgt HeavychainB caggtgcagctggtggaatctagcgacggagtgatgcagcctagcagaagcctgagac SEQID tgagctgtgccgccaacggcttcaccttcaccaaggcctagatgcactaggtacgccaa NO:412 gcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaacagctacg ccacctactacgccgacagcgtgaagggccggacaccatcagccgggacgacagcaa gaacaccagtacctacaaataaacagcctgcaggccgaagacaccgccgtatactact gtcggggcgtgtactatgccctgagccccttcgattactggggccagggaaccctcgtga ccgtgtctagtgacaaaacccataccagagcccacctggtgcagtctggcaccgccatga agaaaccaggcgcactgtgcgggtgtcctgtcagacaagcggctacaccacaccgccc acatcagttaggttccggcaggcccctggcagaagactggaatgggtaggatggatca agccccagtatggcgccgtgaacttcggcagaggcttccgggatagagtgaccctgacc cgggacgtgtaccgcgagatcgcctacatggacatccggggcctgaagcccgataaca ccgccgtgtactactgcgccagagacagaagctacggcgacagcagctgggctctggat gcttggggccagggcacaaccgtggtggtgtctgccgataagacccacaccgccagca caaagggcccatcggtgttccctctggccccttgcagcagaagcaccagcgaatctacag ccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccgtgtcctggaactc tggcgctctgacaagcggcgtgacacctttccagccgtgaccagagcagggcctgta ctctctgagcagcgtcgtgacagtgcccagcagcagcctgagcaccaagacctacacct gtaacgtgaaccacaagcccagcaacaccaaggtggacaagcgagtggaatctaaata cggccctccctgccctccttgcccagcccctgaatttctgggcggaccctccgtgttcctgt tccccccaaagcccaaggacaccctgatgatcagccggacccccgaagtgacctgcgtg gtggtggatgtgtcccaggaagatcccgaggtgcagacaatggtacgtggacggcgtg gaagtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgg gtggtgtccatgctgaccatgctgcaccaggactggctgaacggcaaagagtacaagta caaggtgtccaacaaggacctgcccagaccatcgagaaaaccatcagcaaggccaag ggccagccccgcgagcctcaagttgtaccctgccccctagccaggaagagatgacca agaaccaggtgtccctgagctgtgccgtgaaaggcttctaccccagcgacattgccgtgg aatgggagagcaacggccagcccgagaacaactacaagaccaccccccctgtgagga cagcgacggctcattcacctggtgtccaagagaccgtggacaagagccggtggcagg aaggcaacgtgacagagaccgtgatgcacgagaccctgcacaaccactacacccag aagtccctgtctctgtccagggcaag LightchainB tacatccacgtgacccagancccagcagcctgtccgtgtccatcggcgacagagtgac SEQID catcaactgccagacctctcagggcgtaggcagcgacctgcactgatatcagcacaagc NO:413 ctggcagagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcc cagcagattttccggcagcggcttccacaccagatcaacctgaccatcagcgatctgcag gccgacgacattgccacctactattgtcaggtgagcagacttcggcagaggcagcagac tgcacatcaaggacaaaacccataccgacatcgtgatgacccagacccccctgagcctg agcgtgacacctggacagcctgccagcatcagagcaagagcagccagagcctggtgc acaacaacgccaacacctacctgagaggtatctgagaagcccggccagagccccca gtccagatctacaaggtgtccaacagattcagcggcgtacccgacagattctccggcag cggctctggcaccgacttcaccctgaagatcagccgggtggaagccgaggacgtgggc gtgtactattgtggccagggcacccagtaccccttcacctttggcagcggcaccaaggtg gaaatcaaggataagacccatacccgtacggtggccgctcccagcgtgacatcttcccac ctagcgacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttcta cccccacgaggccaaagtgcagtagaaggtgaacaacgccagcagagcggcaacag ccaggaaagcatgaccgagcaggacagcaaggactccacctacagcctgagcagcac cctgacactgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgacc caccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein46AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:414 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:415 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwi SEQID shegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrd NO:416 yalydddgalnwavdvdylsnlefwgqgtavtvsssqvqlvesgggvvqpgr slrlscaasgftftkawmhwvrqapgkqlewvaqikdksnsyatyyadsvkg rftisrddskntlylqmnslraedtavyycrgvyyalspfdywgqgtlvtvssrta stkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpa peflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgve vhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektis kakgqprepqvctlppsqeemtknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqegnvfscsvmhealhnhytqksls lslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftikisrveaccivgvyycgqgtqypftfgsgtkveikgqpkaa NO:417 pdfvitqsphslsvtpaesasiscksshsiihgdrnnylawyvqkparspqiiiylassra sgvpdrfsgsgsdkdftikisrvetethigtyycniggrespvirtfmtkvdiktkgpsrt vaapsvfifppsdeciiksgtasvvcllnnfypreakvqwkvdnalcisgnsciesvteqd skdsiyslsstitlskadyekhkvyacehqgisspvtksfnrgec BindingProtein46NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:418 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainA gacatccagatgacccagagccccagcagcctgtctgccgcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtatggctgaactggtatcaacagaagc NO:419 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagcccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacattggc cagggcaccaagctggaaatcaagcgtacagtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacnct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgaacaggacagcaaggactccacctacaacctgaacaaca ccctgaccctgagcaaggccgactacgagaagcacaagatgtacgcctgcgaagtgac ccaccagggcctatctagccccgtgaccaagagatcaaccgggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:420 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:421 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein47AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:422 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:423 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwi SEQID shegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrd NO:424 yalydddgalnwavdvdylsnlefwgqgtavtvsssqvqlvesgggvvqpgr slrlscaasgftftkawmhwvrqapgkqlewvaqikdksnsyatyyadsvkg rftisrddskntlylqmnslraedtavyycrgvyyalspfdywgqgtlvtvssrta stkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpa peflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgve vhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektis kakgqprepqvctlppsqeemtknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqegnvfscsvmhealhnhytqksls lslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftikisrveaccivgvyycgqgtqypftfgsgtkveikgqpkaa NO:425 pdfvitqsphslsvtpaesasiscksshsiihgdrnnylawyvqkparspqiiiylassra sgvpdrfsgsgsdkdftikisrvetethigtyycniggrespvirtfmtkvdiktkgpsrt vaapsvfifppsdeciiksgtasvvcllnnfypreakvqwkvdnalcisgnsciesvteqd skdsiyslsstitlskadyekhkvyacehqgisspvtksfnrgec BindingProtein47NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:426 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainA gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:427 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:428 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccag SEQID catcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctgagct NO:429 ggtatctgcagaagcccggccagaacccccagtccctgatctacaagatgtccaacagat tcagcggcgtgcccaacagattctccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccatacctacatc cacgtgacccagagccccagcagcctgtccgtgtccatcggcgacagagtgaccatcaa ctgccagacctctcagagcgtgggcagcgacctgcactagtatcagcacaagcctggca gagcccccaagctgctgatccaccacacaagcagcgtggaagatggcgtgcccagcag attttccggcaacggcttccacaccagatcaacctgaccatcaacgatctgcaggccgac gacattgccacctactattgtcaggtgagcagttatcggcagaggcagcagactacacat caaggataagacccatacccgtacggtggccgctcccagcgtgttcatcttcccacctagc gacgagcagctgaagtccggcacagcctagtcgtgtgcctgctgaacaacttctaccccc gcgaggccaaagtgcagtggaaggtggacaacgccctgcagagcggcaacagccagg aaaacgtgaccgagcaggacaacaaggactccacctacagcctgagcagcaccctaac actgaacaaggccgactacgagaagcacaaggtatacgcctgcgaagtaacccaccag ggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt BindingProtein48AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:430 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:431 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwyrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlykynnsiraedtavyycrgvyyals NO:432 pfdywgqgtlytysssqvhitqsgpevrkpgtsykysckapgntiktydlhwv rsvpg1glqwmgwishegdkkvivertkakvtidwdrstntayiqlsgitsgd tavyycakgskhrirdyalydddgainwaydvdylsniefwgqgtaytyssrt astkgpsvfplapcsrstsestaalgelykdyfpepmswnsgaitsgvhtfpay lgssglyslssyytypssslgtktytcnvdhkpsntkvdkrveskygppcppcp apeflggpsvfifppkpkdtimisapeytcyvydvsqedpevqfimyydgy evhnaktkpreeqfnstyrvvsvitvlhqdvvingkeykekvsnkgipssiekti skakgqprepqvctIppscieemtknqvstscavkgfypsdiavewesnme nnykttppvldsdgsfflvsldtvdksrwqegnvfscsvrnhealhnhytqksls lslgk LightchainB Dfvltqsphslsvtpgesasiscksshslihgdmnylawyvqkpgrspqllassras SEQID gvpdrfsgsgsdkdfilkisrvetedvgtyycatqgrespvirtfgqtttkvdikgqpkaap NO:433 divmtqtplsisvtpggpasisckssgslvlitmantylswykikpggspcisitykvsnrf sgvpdrfsgsgsgtdfilkisneacdvgvyycgqgttpftfgsgtkveiktkgpsrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalgsgnsqcsvtecids kdstystssthiskadyckhkvyaccvthqgisspvtksfargec BindingProtein48NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:434 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagaccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgaaccagctgagaagcgacgacaccaccatgtactactgcacccagt cccactacgacctggattagaacttcgacatgtagggcaagagcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgttccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctccagag cagcggcagtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacatggaccacaaacccagcaacaccaaggtagacaagcgagt ggaatctaagtacggccctccctgccctccttgcccagcccctgaatttctgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccaggaaga gatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggatctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattcacctgtactccaaactgaccgtggacaagaaccaat ggcaggaaggcaacgtgttcagctgaccgtgatacacgaggccagcacaaccactac acccagaagtccctgtctctgtccctgggcaag LightchainA gacatccagatgacccagcagccccagcagcctgtctgccagcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcagaagc NO:435 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagctccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacctttggc cagggcaccaagctggaaatcaagcgtacggtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgagcaggacagcaaggactccacctacaacctgagcagca ccctgaccctgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgac ccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaagcctgagact SEQID gagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactgggtgcgccagg NO:436 cccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaacagctacgc cacctactacgccgacagcgtgaagggccggttcaccatcagccgggacgacagcaag aacaccagtacctgcagatgaacagcctgcgggccgaggacaccgccgtgtactactgt cggggcgtgtactatgccagaacccatcgattactgaggccagagaaccctcgtaacc gtgtctagtagccaggtgcacctgacacagagcggacccgaagtgcggaagcctggca cctctgtgaaggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcact gggtgcgcagcgtgccaggacagggactgcagtggatgggctggatcagccacgagg gcgacaagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacaga agcaccaacaccgcctacctacagagagcggcctaacctctggcgataccgccgtgta ctactgcaccaaaggcagcaagcaccgactgagagactacgccagtacgacgatgac ggcgccagaactgggccgtggatgtgaactacctgagcaacctggaattaggggcca gggcacagccgtgaccgtgtcatctcggaccgccagcacaaagggcccatcggtgttcc ctctggccccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtga aggactactttcccgagcccgtgaccgtgtcctggaactctggcgctagacaagcggcgt gcacacctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgac agtgcccagcagcagcagggcaccaagacctacacctataacgtggaccacaagccc agcaacaccaagatggacaagcgggtagaatctaagtacgaccctccctgccctccttgc ccagcccctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggaca ccctgatgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaa gatcccgaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagac caagcccagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgc tgcaccaggactggctgaacggcaaagagtacaagtgcaaggtatccaacaagagcctg cccagctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaag tgtgtaccctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtg ccgtgaaaggatctaccccagcgacattgccgtggaatgggagagcaacggccagccc gagaacaactacaagaccaccccccctgtgaggacagcgacggctcattcacctggtgt ccaagctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtg atgcacgaggccctgcacaaccactacacccagaagtccctatactgtccctggacaag LightchainB gacttcgtgagacccagagccctcacagcctgagcgtgacacctggcgagagcgccag SEQID catcagagcaagagcagccactccctgatccacggcgaccgaaacaactacctagatg NO:437 gtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagag ccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaag atcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagaga gcccctggacctttggccagggcaccaaggtggacatcaagggccagcccaaggccgc ccccgacatcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctg ccagcatcagctgcaagagcagccagagcctggtgcacaacaacgccaacacctacctg agctggtatctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaac agattcagcggctttgcccgacagattctccggcagcggctctggcaccgacttcacccta aagatcaaccaggtaaaaaccgaggacatgggcgtgtactattatggccagggcaccc agtacccatcaccatgacaacggcaccaaggtggaaatcaagaccaaaggccccagc cgtacggtggccgctcccagcgtgttcatcttcccacctagcgacgagcagctgaagtcc ggcacagcctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcag tggaaggtggacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcag gacagcaaggactccacctacagcctgagcagcaccctgacactgagcaaggccgact acgagaagcacaaggtgtacgcctgcgaagtgacccaccagggcctatctagccccgtg ctccaagaacttcaaccgaagcgagtgt BindingProtein49AminoAcidSequences HeavychainA Qvqlvqsgaevvkpgasvkvsckasgytftsyyihwvrqapgqglewigsiypgnv SEQID ntnyaqkfqgratltvdtsistaymelsrlrsddtavyyctshygldwnfdvwgkgttv NO:438 tvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflg gpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlp pcqeemtkmnqvslwclvkgfypsdiavewesngqpennykttppvldsdgsfflysk ltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Diqmtqspsslsasvgdrvtitcqasqniyvwlnwyqqkpgkapklliykasnlhtgv SEQID psrfsgsgsgtdffitisslqpediatyycqqgqtypytfqqgtkleikrtvaapsvfifpps NO:439 deqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltl skadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwyrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlykynnsiraedtavyycrgvyyals NO:440 pfdywgqgtlytysssqvhitqsgpevrkpgtsykysckapgntiktydlhwv rsvpg1glqwmgwishegdkkvivertkakvtidwdrstntayiqlsgitsgd tavyycakgskhrirdyalydddgainwaydvdylsniefwgqgtaytyssrt astkgpsvfplapcsrstsestaalgelykdyfpepmswnsgaitsgvhtfpay lgssglyslssyytypssslgtktytcnvdhkpsntkvdkrveskygppcppcp apeflggpsvfifppkpkdtimisapeytcyvydvsqedpevqfimyydgy evhnaktkpreeqfnstyrvvsvitvlhqdvvingkeykekvsnkgipssiekti skakgqprepqvcttppscieemtknqvstscavkgfypsdiavewesnme nnykttppvldsdgsfflvsldtvdksrwqegnvfscsvrnhealhnhytqksls lslgk LightchainB Dfvltqsphslsvtpgesasiscksshslihgdmnylawyvqkpgrspqllassras SEQID gvpdrfsgsgsdkdfilkisrvetedvgtyycatqgrespvirtfgqtttkvdikgqpkaap NO:441 divmtqtplsisvtpggpasisckssgslvlitmantylswykikpggspcisitykvsnrf sgvpdrfsgsgsgtdfilkisneacdvgvyycgqgttpftfgsgtkveiktkgpsrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalgsgnsqcsvtecids kdstystssthiskadyckhkvyaccvthqgisspvtksfargec BindingProtein49NucleotideSequences HeavychainA caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:442 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagaccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgaaccagctgagaagcgacgacaccaccatgtactactgcacccagt cccactacgacctggattagaacttcgacatgtagggcaagagcaccaccgtgacagtgt ctagcgcgtcgaccaagggcccctcggtgttccctctggccccttgcagcagaagcacca gcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgaccg tgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctccagag cagcggcagtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggcacca agacctacacctgtaacatggaccacaaacccagcaacaccaaggtagacaagcgagt ggaatctaagtacggccctccctgccctccttgcccagcccctgaatttctgggcggaccc tccgtgttcctgttccccccaaagcccaaggacaccctgatgatcagccggacccccgaa gtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtacg tggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaacag cacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaag agtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcagc aaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccaggaaga gatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggatctaccccagcgacatt gccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattcacctgtactccaaactgaccgtggacaagaaccaat ggcaggaaggcaacgtgttcagctgaccgtgatacacgaggccagcacaaccactac acccagaagtccctgtctctgtccctgggcaag LightchainA gacatccagatgacccagcagccccagcagcctgtctgccagcgtgggcgacagagtga SEQID ccatcacctgtcaggccagccagaacatctacgtgtggctgaactggtatcagcagaagc NO:443 ccggcaaggcccccaagctgctgatctacaaggccagcaacctgcacaccggcgtgcc cagcagattttctggcagcggctccggcaccgacttcaccctgacaatcagctccctgcag cccgaggacattgccacctactactgccagcagggccagacctacccctacacctttggc cagggcaccaagctggaaatcaagcgtacggtggccgctcccagcgtgttcatcttccca cctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctgctgaacaacttct acccccacgaggccaaggtacaatggaaggtggacaatgccctgcagagcagcaaca gccaggaaagcgtaaccgagcaggacagcaaggactccacctacaacctgagcagca ccctgaccctgagcaaggccgactacgagaagcacaaggtgtacgcctgcgaagtgac ccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcgagtgt HeavychainB caggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaagcctgagact SEQID gagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactgggtgcgccagg NO:444 cccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaacagctacgc cacctactacgccgacagcgtgaagggccggttcaccatcagccgggacgacagcaag aacaccagtacctgcagatgaacagcctgcgggccgaggacaccgccgtgtactactgt cggggcgtgtactatgccagaacccatcgattactgaggccagagaaccctcgtaacc gtgtctagtagccaggtgcacctgacacagagcggacccgaagtgcggaagcctggca cctctgtgaaggtgtcctgcaaggcccctggcaacaccctgaaaacctacgacctgcact gggtgcgcagcgtgccaggacagggactgcagtggatgggctggatcagccacgagg gcgacaagaaagtgatcgtggaacggttcaaggccaaagtgaccatcgactgggacaga agcaccaacaccgcctacctacagagagcggcctaacctctggcgataccgccgtgta ctactgcaccaaaggcagcaagcaccgactgagagactacgccagtacgacgatgac ggcgccagaactgggccgtggatgtgaactacctgagcaacctggaattaggggcca gggcacagccgtgaccgtgtcatctcggaccgccagcacaaagggcccatcggtgttcc ctctggccccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtga aggactactttcccgagcccgtgaccgtgtcctggaactctggcgctagacaagcggcgt gcacacctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgac agtgcccagcagcagcagggcaccaagacctacacctataacgtggaccacaagccc agcaacaccaagatggacaagcgggtagaatctaagtacgaccctccctgccctccttgc ccagcccctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggaca ccctgatgatcagccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaa gatcccgaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagac caagcccagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgc tgcaccaggactggctgaacggcaaagagtacaagtgcaaggtatccaacaagagcctg cccagctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaag tgtgtaccctgccccctagccaggaagagatgaccaagaaccaggtgtccctgagctgtg ccgtgaaaggatctaccccagcgacattgccgtggaatgggagagcaacggccagccc gagaacaactacaagaccaccccccctgtgaggacagcgacggctcattcacctggtgt ccaagctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtg atgcacgaggccctgcacaaccactacacccagaagtccctatactgtccctggacaag LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacactggcgagagcgccag SEQID catcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttg NO:445 gtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagag ccagcggcgtgcccgatagattactggcagcggcagcgacaaggacttcaccctgaag atcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagaga gcccctggacctttggccagggcaccaaggtggacatcaaggacaaaacccataccgac atcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccagcat cagctacaagagcagccagagcctgatgcacaacaacgccaacacctacctgagaggt atctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagattca gcggcgtgcccgacagattctccggcagcggctctggcaccgacttcaccctgaagatca gccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtaccc cttcacctttggcagcggcaccaaggtggaaatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatatcccacctagcaacgagcagctgaagtccggcacagc ctctgtcgtatgcctactaaacaacttctacccccgcaaggccaaaatgcagtggaaggta gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaa ggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagag cttcaaccggggcgagtgt BindingProtein50AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:446 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:447 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwi SEQID shegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrd NO:448 yalydddgalnwavdvdylsnlefwgqgtavtvsssqvqlvesgggvvqpgr slrlscaasgftftkawmhwvrqapgkqlewvaqikdksnsyatyyadsvkg rftisrddskntlylqmnslraedtavyycrgvyyalspfdywgqgtlvtvssrta stkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpa peflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgve vhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektis kakgqprepqvctlppsqeemtknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqegnvfscsvmhealhnhytqksls lslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftikisrveaccivgvyycgqgtqypftfgsgtkveikgqpkaa NO:449 pdfvitqsphslsvtpaesasiscksshsiihgdrnnylawyvqkparspqiiiylassra sgvpdrfsgsgsdkdftikisrvetethigtyycniggrespvirtfmtkvdiktkgpsrt vaapsvfifppsdeciiksgtasvvcllnnfypreakvqwkvdnalcisgnsciesvteqd skdsiyslsstitlskadyekhkvyacehqgisspvtksfnrgec BindingProtein50NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:450 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggccac SEQID catcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtggta NO:451 tcagcagaagcccggccaaccccccaagctgctgattttcgccgccaacaacatggaaa gcggcgtgccagccagattttccgacagcggctctggcaccgacttcaccctgaccatca accccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggtacc ctacacctttggccagggcaccaagctggaaatcaagcgtacggtggccgctcccagcg tgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcct gctgaacaacttctacccccgcgaggccaaggtgcagtggaaggtggacaatgccctgc agagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctaca gcctgagcagcaccagaccctgagcaaggccaactacgagaaacacaaggtatacgc ctgcgaagtaacccaccaggacctgtctagccccgtgaccaagagcttcaaccgggacg agtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:452 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacttcgtgctgacccagagccctcacagcctgagcgtgacactggcgagagcgccag SEQID catcagctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttg NO:453 gtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagag ccagcggcgtgcccgatagattactggcagcggcagcgacaaggacttcaccctgaag atcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagaga gcccctggacctttggccagggcaccaaggtggacatcaaggacaaaacccataccgac atcgtgatgacccagacccccctgagcctgagcgtgacacctggacagcctgccagcat cagctacaagagcagccagagcctgatgcacaacaacgccaacacctacctgagaggt atctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagattca gcggcgtgcccgacagattctccggcagcggctctggcaccgacttcaccctgaagatca gccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtaccc cttcacctttggcagcggcaccaaggtggaaatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatatcccacctagcaacgagcagctgaagtccggcacagc ctctgtcgtatgcctactaaacaacttctacccccgcaaggccaaaatgcagtggaaggta gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaa ggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagag cttcaaccggggcgagtgt BindingProtein51AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:454 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:455 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvhltqsgpevrkpgtsvkvsckapgntlktydlhwvrsvpgqglqwmgwi SEQID shegdkkviverfkakvtidwdrstntaylqlsgltsgdtavyycakgskhrlrd NO:456 yalydddgalnwavdvdylsnlefwgqgtavtvsssqvqlvesgggvvqpgr slrlscaasgftftkawmhwvrqapgkqlewvaqikdksnsyatyyadsvkg rftisrddskntlylqmnslraedtavyycrgvyyalspfdywgqgtlvtvssrta stkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpa peflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgve vhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektis kakgqprepqvctlppsqeemtknqvslscavkgfypsdiavewesngqpe nnykttppvldsdgsfflvskltvdksrwqegnvfscsvmhealhnhytqksls lslgk LightchainB Divmtqtplslsvtpgqpasisckssqslvhnnantylswylqkpgspqsliykvsnr SEQID fsgvpdrfsgsgsgtdftikisrveaccivgvyycgqgtqypftfgsgtkveikgqpkaa NO:457 pdfvitqsphslsvtpaesasiscksshsiihgdrnnylawyvqkparspqiiiylassra sgvpdrfsgsgsdkdftikisrvetethigtyycniggrespvirtfmtkvdiktkgpsrt vaapsvfifppsdeciiksgtasvvcllnnfypreakvqwkvdnalcisgnsciesvteqd skdsiyslsstitlskadyekhkvyacehqgisspvtksfnrgec BindingProtein51NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagc NO:458 cacctggaaaaggcctggaatggctgggcgtgatctgggctggcggaggcaccaacta caaccccagcctaaaatccagaaagaccatcagcaaggacaccagcaagaaccaggtg tccctgaagctgagcagcgtgacagccgccgataccgccgtgtactactgcgccagaga caagggctacagctactactacagcatggactactggggccagggcaccaccgtgaccg tgtcatccgcgtcgaccaagggcccctcggtgttccctaggccccttgcagcagaagca ccagcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtga ccgtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctcca gagcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggca ccaagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcg ggtggaatctaagtacggccctccctgccaccttgcccagcccctgaatttctgggcgga ccctccgtgttcctgttccccccaaagcccaagaacaccctgatgatcagccggaccccc gaagtaacctgcgtaatggtggatgtatcccaggaagatcccaaggtgcagttcaattggt acgtggacggcgtgaaaatgcacaacgccaagaccaagcccagagaagaacagttca acagcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggc aaagagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccat cagcaaggccaagggccagccccgcgagcctcaagtgtataccctgcccccttgccag gaagagatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagc gacattgccgtgaaatgggagagcaacgaccagcccaagaacaactacaagaccaccc cccctgtactggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagag ccggtggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaacc actacacccagaagtccctgtctctgtccagggcaag LightchainA gacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggccac SEQID catcacctgtagagccagcgagagcgtggaatattacgtgaccagcctgatgcagtggta NO:459 tcagcagaagcccggccaaccccccaagctgctgattttcgccgccaacaacatggaaa gcggcgtgccagccagattttccgacagcggctctggcaccgacttcaccctgaccatca accccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggtacc ctacacctttggccagggcaccaagctggaaatcaagcgtacggtggccgctcccagcg tgttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcct gctgaacaacttctacccccgcgaggccaaggtgcagtggaaggtggacaatgccctgc agagcggcaacagccaggaaagcgtgaccgagcaggacagcaaggactccacctaca gcctgagcagcaccagaccctgagcaaggccaactacgagaaacacaaggtatacgc ctgcgaagtaacccaccaggacctgtctagccccgtgaccaagagcttcaaccgggacg agtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:460 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacaggacagcctgccag SEQID catcagctgcaaaagcagccagagcctggtgcacaacaacaccaacacctacctgagct NO:461 ggtatctgcagaagcccggccagaacccccagtccagatctacaagatgtccaacagat tcagcggcgtgcccaacagattaccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccataccgacttc gtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccagcatca gctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttggtac gtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagagcca gcggcgtgcccgatagattttaggcagcggcagcgacaaggacttcaccctgaagatca gccgggtggaaaccgaggacgtaagcacctactactgtatgcaggacaaagagagccc ctggacctttggccagggcaccaaggtggacatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatcacccacctagcgacgagcagagaagtccggcacagc ctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtagaaggtg gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacaacaa ggactccacctacagcctgaacaacaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaaaag cttcaaccggggcgagtgt BindingProtein52AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:462 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:463 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwyrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlykynnsiraedtavyycrgvyyals NO:464 pfdywgqgtlytysssqvhitqsgpevrkpgtsykysckapgntiktydlhwv rsvpg1glqwmgwishegdkkvivertkakvtidwdrstntayiqlsgitsgd tavyycakgskhrirdyalydddgainwaydvdylsniefwgqgtaytyssrt astkgpsvfplapcsrstsestaalgelykdyfpepmswnsgaitsgvhtfpay lgssglyslssyytypssslgtktytcnvdhkpsntkvdkrveskygppcppcp apeflggpsvfifppkpkdtimisapeytcyvydvsqedpevqfimyydgy evhnaktkpreeqfnstyrvvsvitvlhqdvvingkeykekvsnkgipssiekti skakgqprepqvcttppscieemtknqvstscavkgfypsdiavewesnme nnykttppvldsdgsfflvsldtvdksrwqegnvfscsvrnhealhnhytqksls lslgk LightchainB Dfvltqsphslsvtpgesasiscksshslihgdmnylawyvqkpgrspqllassras SEQID gvpdrfsgsgsdkdfilkisrvetedvgtyycatqgrespvirtfgqtttkvdikgqpkaap NO:465 divmtqtplsisvtpggpasisckssgslvlitmantylswykikpggspcisitykvsnrf sgvpdrfsgsgsgtdfilkisneacdvgvyycgqgttpftfgsgtkveiktkgpsrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalgsgnsqcsvtecids kdstystssthiskadyckhkvyaccvthqgisspvtksfargec BindingProtein52NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagcc NO:466 acctggaaaaggcctggaatggagggcgtgatctgggctggcggaggcaccaactaca accccagcctgaagtccagaaagaccatcagcaaggacaccagcaagaaccaggtgtc cctgaagctgagcagcgtgacagccaccgataccgccgtatactactacgccagagaca agggctacagctactactacagcatggactactggggccagggcaccaccgtgaccgtg tcatccgcgtcgaccaagggcccctcggtgttccctctggccccttgcagcagaagcacc agcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgacc gtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctccaga gcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggcacc aagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcggg tggaatctaagtacggccctccctgccctccttacccaacccctgaatttagggcggacc ctccgtgttcctgttccccccaaagcccaaggacaccagatgatcaaccggacccccga agtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtac gtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaaca gcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaa gagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcag caaggccaagggccaaccccacgagcctcaaatgtataccctaccccatgccaggaaa agatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagcgacat tgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctgggcaag LightchainA gacatcgtgctgacacagagccctgctagcctggccgtgtctcctggacagagggccac SEQID catcacctgtagagccagcgagagcgtgaatattacgtgaccagcctgatgcagtggtat NO:467 cagcagaagcccggccagccccccaagctgctgatatcgccgccaacaacgtggaaaa cggcgtgccagccagattttccggcagcggctctggcaccaacttcaccctgaccatcaa ccccgtggaagccaacgacgtggccaactactactgccagcagagccggaaggtgccc tacacctttggccagggcaccaagaggaaatcaagcgtacggtggccgctcccagcgt gttcatcttcccacctagcgacgagcagctgaagtccggcacagcctctgtcgtgtgcctg ctgaacaacttctacccccgcgaggccaaggtgcagtggaaggtggacaatgccctgca gagcggcaacagccaggaaaacgtgaccgagcaggacagcaaggactccacctacag cctgagcagcaccctgaccctgagcaaggccgactacgagaagcacaaggtgtacgcct gcgaagtgacccaccagggcctgtctagccccgtgaccaagagcttcaaccggggcga gtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:468 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacatcgtgatgacccagacccccctgagcctgagcgtgacacaggacagcctgccag SEQID catcagctgcaaaagcagccagagcctggtgcacaacaacaccaacacctacctgagct NO:469 ggtatctgcagaagcccggccagaacccccagtccagatctacaagatgtccaacagat tcagcggcgtgcccaacagattaccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccataccgacttc gtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccagcatca gctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttggtac gtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagagcca gcggcgtgcccgatagattttaggcagcggcagcgacaaggacttcaccctgaagatca gccgggtggaaaccgaggacgtaagcacctactactgtatgcaggacaaagagagccc ctggacctttggccagggcaccaaggtggacatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatcacccacctagcgacgagcagagaagtccggcacagc ctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtagaaggtg gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacaacaa ggactccacctacagcctgaacaacaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaaaag cttcaaccggggcgagtgt BindingProtein53AminoAcidSequences HeavychainA Qvqlqesgpglvkpsqtlsltctvsgfslsdygvhwvrqppgkglewlgviwagggt SEQID nynpslksrktiskdtsknqvslklssvtaadtavyycardkgysyyysmdywgqgtt NO:470 vtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpav lqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapefl ggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkp reeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvyt lppcqeemtknqvslwclvkgfypsdiavewesngqpennykttppvldsdgsffly skltvdksrwqegnvfscsvmhealhnhytqkslslslgk LightchainA Divltqspaslavspgqratitcrasesveyyvtslmqwyqqkpgqppkllifaasnve SEQID sgvparfsgsgsgtdftltinpveandvanyycqqsrkvpytfgqgtkleikrtvaapsv NO:471 fifppsdeqlksgtasvvcllnnfypreakvqwkydnalqsgnsqesvteqdskdstys lsstltskadyekhkvyacevthqglsspvtksfnrgec HeavychainB Qvqlvesgggvvqpgrslrlscaasgftftkawmhwyrqapgkqlewvaqi SEQID kdksnsyatyyadsvkgrftisrddskntlykynnsiraedtavyycrgvyyals NO:472 pfdywgqgtlytysssqvhitqsgpevrkpgtsykysckapgntiktydlhwv rsvpg1glqwmgwishegdkkvivertkakvtidwdrstntayiqlsgitsgd tavyycakgskhrirdyalydddgainwaydvdylsniefwgqgtaytyssrt astkgpsvfplapcsrstsestaalgelykdyfpepmswnsgaitsgvhtfpay lgssglyslssyytypssslgtktytcnvdhkpsntkvdkrveskygppcppcp apeflggpsvfifppkpkdtimisapeytcyvydvsqedpevqfimyydgy evhnaktkpreeqfnstyrvvsvitvlhqdvvingkeykekvsnkgipssiekti skakgqprepqvcttppscieemtknqvstscavkgfypsdiavewesnme nnykttppvldsdgsfflvsldtvdksrwqegnvfscsvrnhealhnhytqksls lslgk LightchainB Dfvltqsphslsvtpgesasiscksshslihgdmnylawyvqkpgrspqllassras SEQID gvpdrfsgsgsdkdfilkisrvetedvgtyycatqgrespvirtfgqtttkvdikgqpkaap NO:473 divmtqtplsisvtpggpasisckssgslvlitmantylswykikpggspcisitykvsnrf sgvpdrfsgsgsgtdfilkisneacdvgvyycgqgttpftfgsgtkveiktkgpsrtv aapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalgsgnsqcsvtecids kdstystssthiskadyckhkvyaccvthqgisspvtksfnrgec BindingProtein53NucleotideSequences HeavychainA caggtgcagctgcaggaatctggccctggcctcgtgaagcctagccagaccctgagcct SEQID gacctgtaccgtgtccggcttcagcctgagcgactacggcgtgcactgggtgcgccagcc NO:474 acctggaaaaggcctggaatggagggcgtgatctgggctggcggaggcaccaactaca accccagcctgaagtccagaaagaccatcagcaaggacaccagcaagaaccaggtgtc cctgaagctgagcagcgtgacagccaccgataccgccgtatactactacgccagagaca agggctacagctactactacagcatggactactggggccagggcaccaccgtgaccgtg tcatccgcgtcgaccaagggcccctcggtgttccctctggccccttgcagcagaagcacc agcgaatctacagccgccctgggctgcctcgtgaaggactactttcccgagcccgtgacc gtgtcctggaactctggcgctctgacaagcggcgtgcacacctttccagccgtgctccaga gcagcggcctgtactctctgagcagcgtcgtgacagtgcccagcagcagcctgggcacc aagacctacacctgtaacgtggaccacaagcccagcaacaccaaggtggacaagcggg tggaatctaagtacggccctccctgccctccttacccaacccctgaatttagggcggacc ctccgtgttcctgttccccccaaagcccaaggacaccagatgatcaaccggacccccga agtgacctgcgtggtggtggatgtgtcccaggaagatcccgaggtgcagttcaattggtac gtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaaca gcacctaccgggtggtgtccgtgctgaccgtgctgcaccaggactggctgaacggcaaa gagtacaagtgcaaggtgtccaacaagggcctgcccagctccatcgagaaaaccatcag caaggccaagggccaaccccacgagcctcaaatgtataccctaccccatgccaggaaa agatgaccaagaaccaggtgtccctgtggtgtctcgtgaaaggcttctaccccagcgacat tgccgtggaatgggagagcaacggccagcccgagaacaactacaagaccaccccccct gtgctggacagcgacggctcattcttcctgtactccaagctgaccgtggacaagagccggt ggcaggaaggcaacgtgttcagctgctccgtgatgcacgaggccctgcacaaccactac acccagaagtccctgtctctgtccctgggcaag LightchainA gacatcgtgatgacccagacccccctgagcctgagcgtgacacaggacagcctgccag SEQID catcagctgcaaaagcagccagagcctggtgcacaacaacaccaacacctacctgagct NO:475 ggtatctgcagaagcccggccagaacccccagtccagatctacaagatgtccaacagat tcagcggcgtgcccaacagattaccggcagcggctaggcaccgacttcaccctaaaaa tcagccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtac cccttcacctttggcagcggcaccaaggtggaaatcaaggacaaaacccataccgacttc gtgctgacccagagccctcacagcctgagcgtgacacctggcgagagcgccagcatca gctgcaagagcagccactccctgatccacggcgaccggaacaactacctggcttggtac gtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagagcca gcggcgtgcccgatagattttaggcagcggcagcgacaaggacttcaccctgaagatca gccgggtggaaaccgaggacgtaagcacctactactgtatgcaggacaaagagagccc ctggacctttggccagggcaccaaggtggacatcaaggataagacccatacccgtacggt ggccgctcccagcgtgttcatcacccacctagcgacgagcagagaagtccggcacagc ctctgtcgtgtgcctgctgaacaacttctacccccgcgaggccaaagtgcagtagaaggtg gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacaacaa ggactccacctacagcctgaacaacaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaaaag cttcaaccggggcgagtgt HeavychainB caggtgcagctggtgcagtctggcgccgaggtcgtgaaacctggcgcctctgtgaaggt SEQID gtcctgcaaggccagcggctacacctttaccagctactacatccactgggtgcgccaggc NO:476 ccctggacagggactggaatggatcggcagcatctaccccggcaacgtgaacaccaact acgcccagaagttccagggcagagccaccctgaccgtggacaccagcatcagcaccgc ctacatggaactgagccggctgagaagcgacgacaccgccgtgtactactgcacccggt cccactacggcctggattggaacttcgacgtgtggggcaagggcaccaccgtgacagtg tctagcagccaggtgcagctggtggaatctggcggcggagtggtgcagcctggcagaa gcctgagactgagctgtgccgccagcggcttcaccttcaccaaggcctggatgcactggg tgcgccaggcccctggaaagcagctggaatgggtggcccagatcaaggacaagagcaa cagctacgccacctactacgccgacagcgtgaagggccggttcaccatcagccgggac gacagcaagaacaccctgtacctgcagatgaacagcctgcgggccgaggacaccgccg tgtactactgtcggggcgtgtactatgccctgagccccttcgattactggggccagggaac cctcgtgaccgtgtctagtcggaccgccagcacaaagggcccatcggtgttccctctggc cccttgcagcagaagcaccagcgaatctacagccgccctgggctgcctcgtgaaggact actttcccgagcccgtgaccgtgtcctggaactctggcgctctgacaagcggcgtgcaca cctttccagccgtgctccagagcagcggcctgtactctctgagcagcgtcgtgacagtgcc cagcagcagcctgggcaccaagacctacacctgtaacgtggaccacaagcccagcaac accaaggtggacaagcgggtggaatctaagtacggccctccctgccctccttgcccagcc cctgaatttctgggcggaccctccgtgttcctgttccccccaaagcccaaggacaccctga tgatcaaccggacccccgaagtgacctgcgtggtggtggatgtgtcccaggaagatccc gaggtgcagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcc cagagaggaacagttcaacagcacctaccgggtggtgtccgtgctgaccgtgctgcacc aggactggctgaacggcaaagagtacaagtgcaaggtgtccaacaagggcctgcccag ctccatcgagaaaaccatcagcaaggccaagggccagccccgcgagcctcaagtgtgta ccctgccccctagccaggaagagatgaccaagaaccaagtgtccctgagctgtgccgtg aaaggcttctaccccagcgacattgccgtggaatgggagagcaacggccagcccgaga acaactacaagaccaccccccctgtgctggacaacgacggctcattcttcctggtatccaa gctgaccgtggacaagagccggtggcaggaaggcaacgtgttcagctgctccgtgatgc acgaggccctgcacaaccactacacccagaagtccctgtctctgtccctgggcaag LightchainB gacttcgtgagacccaaagccctcacagcctgagcatgacacctggcgagagcgccag SEQID catcagctgcaaaagcagccactccctgatccacggcgaccgaaacaactacctagcttg NO:477 gtacgtgcagaagcccggcagatccccccagctgctgatctacctggccagcagcagag ccagcggcgtgcccgatagattttctggcagcggcagcgacaaggacttcaccctgaag atcagccgggtggaaaccgaggacgtgggcacctactactgtatgcagggcagagaga gcccctggacctttagccagggcaccaagatggacatcaagaacaaaacccataccgac atcgtgatgacccagacccccagagcctgaacgtgacacctgaacagcctaccagcat cagctgcaagagcagccagagcctggtacacaacaacgccaacacctacctgagctggt atctgcagaagcccggccagagcccccagtccctgatctacaaggtgtccaacagattca gcggcgtgcccgacagattctccggcagcggctctggcaccgacttcaccctgaagatca gccgggtggaagccgaggacgtgggcgtgtactattgtggccagggcacccagtaccc cttcacctttggcagcggcaccaaggtggaaatcaaggataagacccatacccgtacggt ggccactcccagcgtgttcatcttcccacctaacgacgagcagctgaagtccgacacagc ctctgtcgtgtgcctgctgaacaacttctacccccgcgagaccaaagtacagtggaagatg gacaacgccctgcagagcggcaacagccaggaaagcgtgaccgagcaggacagcaa ggactccacctacagcctgagcagcaccctgacactgagcaaggccgactacgagaag cacaaggtgtacgcctgcgaagtgacccaccagggcctgtctagccccgtgaccaagag cttcaaccggggcgagtgt

TABLE-US-00012 TABLEA CDRsequencesofbindingproteins Ab CDRH1 CDRH2 CDRH3 CDRL1 CDRL2 CDRL3 CD4BSa dctln wikprggavnyarplqg gkncdynwdfeh rtsqyglsa sgstraa qqyef (SEQIDNO:248) (SEQIDNO:249) (SEQIDNO:250) (SEQIDNO:266) (SEQIDNO:267) (SEQIDNO:268) CD4BSb GYTFTAHI IKPQYGAV drsygdsswalda QGVGSD HTS qvlqf (SEQIDNO:251) (SEQIDNO:252) (SEQIDNO:253) (SEQIDNO:269) (SEQIDNO:270) (SEQIDNO:271) MPER gfdfdnaw itgpggwssv tgkyydfwsgyppgeeyfqd rgdslrshyas gknnrps ssrdksgsrlsv (SEQIDNO:254) (SEQIDNO:255) (SEQIDNO:256) (SEQIDNO:272) (SEQIDNO:273) (SEQIDNO:274) V1/V2dir. GNTLKTYD ISHEGDKK cakgskhrlrdyalyddd hslihgdrnny las cmqgrespwtf a (SEQIDNO:257) (SEQIDNO:258) galnwavdvdylsnlefw (SEQIDNO:275) (SEQIDNO:276) (SEQIDNO:277) (SEQIDNO:259) V3dir. SGASISDSY VHKSGDT ARTLHGRRIYGIVAFNEWF SLGSRA NNQ HIWDSRVPTKWV (SEQIDNO:260) (SEQIDNO:261) TYFYMDV (SEQIDNO:278) (SEQIDNO:279) (SEQIDNO:280) (SEQIDNO:262) V1/Vdir. QFRFDGYG ISHDGIKK CAKDLREDECEEWWSDYY TSNIGNNF ETD atwaaslssarv b (SEQIDNO:263) (SEQIDNO:264) DFGKQLPCAKSRGGLVGIA (SEQIDNO:281) (SEQIDNO:282) (SEQIDNO:283) DNW (SEQIDNO:265) Ab CDRH1 CDRH2 CDRH3 CDRL1 CDRL2 CDRL3 Anti-CD28 GYTFTSYY IYPGNVNT trshygldwnfdv QNIYVW KAS qqgqtypyt (SEQIDNO:479) (SEQIDNO:480) (SEQIDNO:481) (SEQIDNO:488) (SEQIDNO:489) (SEQIDNO:490) Anti-CD28 GFSLSDYG IWAGGGT ardkgysyyysmd ESVEYYVTSL AAS qqsrkvpyt (SEQIDNO:482) (SEQIDNO:483) (SEQIDNO:484) (SEQIDNO:491) (SEQIDNO:492) (SEQIDNO:493) Anti-CD3 GFTFTKAW IKDKSNS rgvyyalspfdy QSLVHNNANTY KVS gqgtqyp (SEQIDNO:485) (SEQIDNO:486) (SEQIDNO:487) (SEQIDNO:494) (SEQIDNO:495) (SEQIDNO:496)

TABLE-US-00013 TABLEB CDR sequences of parental antibodies Ab CDR_H1 CDR_H2 CDR_H3 CDR_L1 CDR_L2 CDR_L3 CD4BSa DCTLN LKPRGGAVNYARP GKNCDYNWDFEH RTSQYGLSA SGSTRAA QQYEF (SEQIDNO:248) LQ (SEQIDNO:250) (SEQIDNO:266) (SEQIDNO:267) (SEQIDNO:268) (SEQIDNO:497) CD4BSb GYTFTAHI IKPQYGAV DRSYGDSSWALDA QGVGSD HTS QVLQF (SEQIDNO:251) (SEQIDNO:252) (SEQIDNO:253) (SEQIDNO:269) (SEQIDNO:270) (SEQIDNO:271) MPER GFDFDNAW ITGPGGWSSV TGKYYDFWSGYPPGEEYFQ SLRSHY GKN SSRDKSGSRLSV (SEQIDNO:254) (SEQIDNO:255) D (SEQIDNO:500) (SEQIDNO:501) (SEQIDNO:274) (SEQIDNO:256) MPER_100W GFDFDNAW ITGPGGWSSV TGKYYDFWWGYPPGEEYF SLRSHY GKN SSRDKSGSRLSV (SEQIDNO:254) (SEQIDNO:255) QD (SEQIDNO:500) (SEQIDNO:501) (SEQIDNO:274) (SEQIDNO:259) V1/V2 GNTLKTYD ISHEGDKK CAKGSKHRLRDYALYDDD HSLIHGDRNNY LAS CMQGRESPWTF directeda (SEQIDNO:257) (SEQIDNO:258) GALNWAVDVDYLSNLEFW (SEQIDNO:275) (SEQIDNO:276) (SEQIDNO:277) (SEQIDNO:259) V1/V2 QFRFDGYG ISHDGIKK CAKDLREDECEEWWSDYY TSNIGNNF ETD ATWAASLSSAR directedb (SEQIDNO:263) (SEQIDNO:264) DFGKQLPCAKSRGGLVGIA (SEQIDNO:281) (SEQIDNO:282) V DNW (SEQIDNO:283) (SEQIDNO:265) V3 GASISDSY VHKSGDT ARTLHGRRIYGIVAFNEWF SLGSRA NNQ HIWDSRVPTKW directed (SEQIDNO:499) (SEQIDNO:261) TYFYMDV (SEQIDNO:278) (SEQIDNO:279) V (SEQIDNO:262) (SEQIDNO:280) CD28 GYTFTSYY IYPGNVNT TRSHYGLDWNFDV QNIYVW KAS QQGQTYPYT (SEQIDNO:479) (SEQIDNO:480) (SEQIDNO:481) (SEQIDNO:488) (SEQIDNO:489) (SEQIDNO:490) CD28_2 GFSLSDYG IWAGGGT ARDKGYSYYYSMD ESVEYYVTSL AAS QQSRKVPYT (SEQIDNO:482) (SEQIDNO:483) (SEQIDNO:484) (SEQIDNO:491) (SEQIDNO:492) (SEQIDNO:493) CD3 GFTFTKAW IKDKSNS RGVYYALSPFDY QSLVHNNANTY KVS GQGTQYP (SEQIDNO:485) (SEQIDNO:486) (SEQIDNO:487) (SEQIDNO:494) (SEQIDNO:495) (SEQIDNO:496)

TABLE-US-00014 TABLEC Variabledomainsequencesofparentalantibodies AbName V.sub.H V.sub.L CD4BSa QVQLVQSGGQMKKPGESMRISCRASGYEFIDCTLNWIRLAP EIVLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQ GKRPEWMGWLKPRGGAVNYARPLQGRVTMTRDVYSDTAF RPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNL LELRSLTVDDTAVYFCTRGKNCDYNWDFEHWGRGTPVIV TISNLESGDFGVYYCQQYEFFGQGTKVQVDIK S (SEQIDNO:512) (SEQIDNO:502) CD4BSb RAHLVQSGTAMKKPGASVRVSCQTGYTFTAHILFWFRQAP YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHW GRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAY YQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTS MDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVV FNLTISDLQADDIATYYCQVLQFFGRGSRLHIK VSA (SEQIDNO:513) (SEQIDNO:503) CD4BSb RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAP YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHW (?glycan) GRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAY YQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTS MDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVV F LTISDLQADDIATYYCQVLQFFGRGSRLHIK VSA (SEQIDNO:514) (SEQIDNO:503) CD4BSb RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAP YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHW (?isomerization GRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAY YQHKPGRAPKLLIHHTSSVE GVPSRFSGSGFHTS D55E) MDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVV FNLTISDLQADDIATYYCQVLQFFGRGSRLHIK VSA (SEQIDNO:515) (SEQIDNO:503) CD4BSb RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAP YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLWH (?isomerization GRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAY YQHKPGRAPKLLIHHTSSVED VPSRFSGSGFHTS G56A) MDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVV FNLTISDLQADDIATYYCQVLQFFGRGSRLHIK VSA (SEQIDNO:516) (SEQIDNO:503) CD4BSb RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAP YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHW (?glycan/ GRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAY YQHKPGRAPKLLIHHTSSVE GVPSRFSGSGFHTS ?isomerization MDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVV F LTISDLQADDIATYYCQVLQFFGRGSRLHIK D55E) VSA (SEQIDNO:517) (SEQIDNO:503) MPER EVRLVESGGGLVKPGGSLRLSCSASGFDFDNAWMTWVRQP ASELTQDPAVSVALKQTVTITCRGDSLRSHYASW PGKGLEWVGRITGPGEGWSVDYAESVKGRFTISRDNTKNTL YQKKPGQAPVLLFYGKNNRPSGIPDRFSGSASGN YLEMNNVRTEDTGYYFCARTGKYYDFWSGYPPGEEYFQD RASLTITGAQAEDEADYYCSSRDKSGSRLSVFGG WGQGTLVIVSS GTKLTVL (SEQIDNO:504) (SEQIDNO:518) MPER_100W EVRLVESGGGLVKPGGSLRLSCSASGFDFDNAWMTWVRQP ASELTQDPAVSVALKQTVTITCRGDSLRSHYASW PGKGLEWVGRITGPGEGWSVDYAESVKGRFTISRDNTKNTL YQKKPGQAPVLLFYGKNNRPSGIPDRFSGSASGN YLEMNNVRTEDTGYYFCARTGKYYDFW GYPPGEEYFQD RASLTITGAQAEDEADYYCSSRDKSGSRLSVFGG WGQGTLVIVSS GTKLTVL (SEQIDNO:505) (SEQIDNO:518) V1/V2 QVHLTQSGPEVRKPGTSVKVSCKAPGNTLKTYDLHWVRSV DFVLTQSPHSLSVTPGESASISCKSSHSLIHGDRNN directeda PGQGLQWMGWISHEGDKKVIVERFKAKVTIDWDRSTNTAY YLAWYVQKPGRSPQLLIYLASSRASGVPDRFSGS LQLSGLTSGDTAVYYCAKGSKHRLRDYALYDDDGALNWA GSDKDFTLKISRVETEDVGTYYCMQGRESPWTFG VDVDYLSNLEFWGQGTAVTVSS QGTKVDIK (SEQIDNO:506) (SEQIDNO:519) V1/V2 QVQLVESGGGVVQPGTSLRLSCAASQFRFGDYGMHWVRQ QSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVS directedb APGKGLEWVASISHDGIKKYHAEKVWGRFTISRDNSKNTLY WYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGT LQMNSLRPEDTALYYCAKDLREDECEEWWSDYYDFGKQLP SGTLAITGLQTGDEADYYCATWAASLSSARVFGT CAKSRGGLVGIADNWGQGTMVTVSS GTKVIVL (SEQIDNO:507) (SEQIDNO:520) V3 QMQLQESGPGLVKPSETLSLTCSVSGASISDSYWSWIRRSPG SDISVAPGETARISCGEKSLGSRAVQWYQHRAGQ directed KGLEWIGYVHKSGDTNYSPSLKSRVNLSLDTSKNQVSLSLV APSLIIYNNQDRPSGIPERFSGSPDSPFGTTATLTIT AATAADSGKYYCARTLHGRRIYGIVAFNEWFTYFYMDVW SVEAGDEADYYCHIWDSRVPTKWVFGGGTTLTV GNGTQVTVSS G (SEQIDNO:508) (SEQIDNO:521) CD28 QVQLVQSGAEVVKPGASVKVSCKASGYTFTSYYIHWVRQA DIQMTQSPSSLSASVGDRVTITCQASQNIYVWLN PGQGLEWIGSIYPGNVNTNYAQKRQGRATLTVDTSISTAYM WYQQKPGKAPKLLIYKASNLHTGVPSRFSGSGSG ELSRLRSDDTAVYYCTRSHYGLDWNFDVWGKGTTVTVSS TDFTLTISSLQPEIATYYCCQQGQTYPYTFGQGTK (SEQIDNO:509) LEIK (SEQIDNO:522) CD28_2 QVQLQESGPGLVKPSQTLSLTCTVSGFSLSDYGVHWVRQPP DIVLTTQSPASLAVSPGQRATITCRASESVEYYVTS GKGLEWLGVIWAGGGTNYNPSLKSRKTISKDTSKNQVSLKL LMQWYQQKPGQPPKLLIFAASNVESGVPARFSGS SSVTAADTAVYYCARDKGYSYYYSMDYWGQGTTVTVSS GSGTDFTLTINPVEANDVANYYCQQSRKVPYTFG (SEQIDNO:510) QGTKLEIK (SEQIDNO:523) CD3 QVQLVESGGGVVQPGRSLRLSCAASGFTFTKAWMHWVRQ DIVMTQTPLSLSVTPGQPASISCKSSQSLVHNNAN APGKQLEWVAQIKDKSNSYATYYADSVKGRFTISRDDSKNT TYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGS LYLQMNSLRAEDTAVYYCRGVYYALSPFDYWGQGTLVTV GSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFG SS SGTKVEIK (SEQIDNO:511) (SEQIDNO:524) CDR sequences are underlined. Variable domain modifications are shown in bold and italicized.