Binding molecules for BCMA and CD3

Abstract

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule.

Claims

1. A nucleic acid encoding a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein (a) the first binding domain is capable of binding to epitope cluster 3 and to epitope cluster 4 of B cell maturation antigen (BCMA); and (b) the second binding domain is capable of binding to the T cell CD3 receptor complex; and wherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002, and epitope cluster 4 of BCMA corresponds to amino acid residues 42 to 54 of the sequence as depicted in SEQ ID NO: 1002, and wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of: (a) CDR-H1 as depicted in SEQ ID NO: 231, CDR-H2 as depicted in SEQ ID NO: 232, CDR-H3 as depicted in SEQ ID NO: 233, CDR-L1 as depicted in SEQ ID NO: 234, CDR-L2 as depicted in SEQ ID NO: 235 and CDR-L3 as depicted in SEQ ID NO: 236; (b) CDR-H1 as depicted in SEQ ID NO: 241, CDR-H2 as depicted in SEQ ID NO: 242, CDR-H3 as depicted in SEQ ID NO: 243, CDR-L1 as depicted in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245 and CDR-L3 as depicted in SEQ ID NO: 246; (c) CDR-H1 as depicted in SEQ ID NO: 251, CDR-H2 as depicted in SEQ ID NO: 252, CDR-H3 as depicted in SEQ ID NO: 253, CDR-L1 as depicted in SEQ ID NO: 254, CDR-L2 as depicted in SEQ ID NO: 255 and CDR-L3 as depicted in SEQ ID NO: 256; (d) CDR-H1 as depicted in SEQ ID NO: 261, CDR-H2 as depicted in SEQ ID NO: 262, CDR-H3 as depicted in SEQ ID NO: 263, CDR-L1 as depicted in SEQ ID NO: 264, CDR-L2 as depicted in SEQ ID NO: 265 and CDR-L3 as depicted in SEQ ID NO: 266; (e) CDR-H1 as depicted in SEQ ID NO: 271, CDR-H2 as depicted in SEQ ID NO: 272, CDR-H3 as depicted in SEQ ID NO: 273, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276; (f) CDR-H1 as depicted in SEQ ID NO: 281, CDR-H2 as depicted in SEQ ID NO: 282, CDR-H3 as depicted in SEQ ID NO: 283, CDR-L1 as depicted in SEQ ID NO: 284, CDR-L2 as depicted in SEQ ID NO: 285 and CDR-L3 as depicted in SEQ ID NO: 286; (g) CDR-H1 as depicted in SEQ ID NO: 291, CDR-H2 as depicted in SEQ ID NO: 292, CDR-H3 as depicted in SEQ ID NO: 293, CDR-L1 as depicted in SEQ ID NO: 294, CDR-L2 as depicted in SEQ ID NO: 295 and CDR-L3 as depicted in SEQ ID NO: 296; (h) CDR-H1 as depicted in SEQ ID NO: 301, CDR-H2 as depicted in SEQ ID NO: 302, CDR-H3 as depicted in SEQ ID NO: 303, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 306; (i) CDR-H1 as depicted in SEQ ID NO: 391, CDR-H2 as depicted in SEQ ID NO: 392, CDR-H3 as depicted in SEQ ID NO: 393, CDR-L1 as depicted in SEQ ID NO: 394, CDR-L2 as depicted in SEQ ID NO: 395 and CDR-L3 as depicted in SEQ ID NO: 396; (k) CDR-H1 as depicted in SEQ ID NO: 401, CDR-H2 as depicted in SEQ ID NO: 402, CDR-H3 as depicted in SEQ ID NO: 403, CDR-L1 as depicted in SEQ ID NO: 404, CDR-L2 as depicted in SEQ ID NO: 405 and CDR-L3 as depicted in SEQ ID NO: 406; (l) CDR-H1 as depicted in SEQ ID NO: 411, CDR-H2 as depicted in SEQ ID NO: 412, CDR-H3 as depicted in SEQ ID NO: 413, CDR-L1 as depicted in SEQ ID NO: 414, CDR-L2 as depicted in SEQ ID NO: 415 and CDR-L3 as depicted in SEQ ID NO: 416; (m) CDR-H1 as depicted in SEQ ID NO: 421, CDR-H2 as depicted in SEQ ID NO: 422, CDR-H3 as depicted in SEQ ID NO: 423, CDR-L1 as depicted in SEQ ID NO: 424, CDR-L2 as depicted in SEQ ID NO: 425 and CDR-L3 as depicted in SEQ ID NO: 426; (n) CDR-H1 as depicted in SEQ ID NO: 431, CDR-H2 as depicted in SEQ ID NO: 432, CDR-H3 as depicted in SEQ ID NO: 433, CDR-L1 as depicted in SEQ ID NO: 434, CDR-L2 as depicted in SEQ ID NO: 435 and CDR-L3 as depicted in SEQ ID NO: 436; (o) CDR-H1 as depicted in SEQ ID NO: 441, CDR-H2 as depicted in SEQ ID NO: 442, CDR-H3 as depicted in SEQ ID NO: 443, CDR-L1 as depicted in SEQ ID NO: 444, CDR-L2 as depicted in SEQ ID NO:445 and CDR-L3 as depicted in SEQ ID NO: 446; (p) CDR-H1 as depicted in SEQ ID NO: 451, CDR-H2 as depicted in SEQ ID NO: 452, CDR-H3 as depicted in SEQ ID NO: 453, CDR-L1 as depicted in SEQ ID NO: 454, CDR-L2 as depicted in SEQ ID NO: 455 and CDR-L3 as depicted in SEQ ID NO: 456; (q) CDR-H1 as depicted in SEQ ID NO: 461, CDR-H2 as depicted in SEQ ID NO: 462, CDR-H3 as depicted in SEQ ID NO: 463, CDR-L1 as depicted in SEQ ID NO: 464, CDR-L2 as depicted in SEQ ID NO: 465 and CDR-L3 as depicted in SEQ ID NO: 466; (r) CDR-H1 as depicted in SEQ ID NO: 471, CDR-H2 as depicted in SEQ ID NO: 472, CDR-H3 as depicted in SEQ ID NO: 473, CDR-L1 as depicted in SEQ ID NO: 474, CDR-L2 as depicted in SEQ ID NO: 475 and CDR-L3 as depicted in SEQ ID NO: 476; (s) CDR-H1 as depicted in SEQ ID NO: 481, CDR-H2 as depicted in SEQ ID NO: 482, CDR-H3 as depicted in SEQ ID NO: 483, CDR-L1 as depicted in SEQ ID NO: 484, CDR-L2 as depicted in SEQ ID NO: 485 and CDR-L3 as depicted in SEQ ID NO: 486; (t) CDR-H1 as depicted in SEQ ID NO: 491, CDR-H2 as depicted in SEQ ID NO: 492, CDR-H3 as depicted in SEQ ID NO: 493, CDR-L1 as depicted in SEQ ID NO: 494, CDR-L2 as depicted in SEQ ID NO: 495 and CDR-L3 as depicted in SEQ ID NO: 496; and (u) CDR-H1 as depicted in SEQ ID NO: 501, CDR-H2 as depicted in SEQ ID NO: 502, CDR-H3 as depicted in SEQ ID NO: 503, CDR-L1 as depicted in SEQ ID NO: 504, CDR-L2 as depicted in SEQ ID NO: 505 and CDR-L3 as depicted in SEQ ID NO: 506.

2. A vector comprising the nucleic acid as defined in claim 1.

3. A host cell transformed or transfected with the nucleic acid as defined in claim 1.

4. A process for the production of a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein (a) the first binding domain is capable of binding to epitope cluster 3 and to epitope cluster 4 of BCMA; and (b) the second binding domain is capable of binding to the T cell CD3 receptor complex; and wherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002, and epitope cluster 4 of BCMA corresponds to amino acid residues 42 to 54 of the sequence as depicted in SEQ ID NO: 1002, said process comprising culturing the host cell as defined in claim 3 under conditions allowing the expression of the binding molecule and recovering the produced binding molecule from the culture.

5. The nucleic acid of claim 1, wherein the first binding domain is not capable of binding to the chimeric extracellular domain of BCMA as depicted in SEQ ID NO: 1015.

6. The nucleic acid of claim 1, wherein the first binding domain is further capable of binding to macaque BCMA.

7. The nucleic acid of claim 1, wherein the second binding domain is capable of binding to CD3 epsilon.

8. The nucleic acid of claim 1, wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.

9. The nucleic acid of claim 1, wherein the first and/or the second binding domain are from an antibody.

10. The nucleic acid of claim 9, wherein the first and/or the second binding domain is selected from the group consisting of (scFv).sub.2, (single domain mAb).sub.2, scFv-single domain mAb, diabodies and oligomers thereof.

11. The nucleic acid of claim 1, wherein the first binding domain comprises a VH region selected from the group consisting of VH regions as depicted in SEQ ID NO: 237, SEQ ID NO: 247, SEQ ID NO: 257, SEQ ID NO: 267, SEQ ID NO: 277, SEQ ID NO: 287, SEQ ID NO: 297, SEQ ID NO: 307, SEQ ID NO: 397, SEQ ID NO: 407, SEQ ID NO: 417, SEQ ID NO: 427, SEQ ID NO: 437, SEQ ID NO: 447, SEQ ID NO: 457, SEQ ID NO: 467, SEQ ID NO: 477, SEQ ID NO: 487, SEQ ID NO: 497, and SEQ ID NO: 507.

12. The nucleic acid of claim 1, wherein the first binding domain comprises a VL region selected from the group consisting of VL regions as depicted in SEQ ID NO: 238, SEQ ID NO: 248, SEQ ID NO: 258, SEQ ID NO: 268, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 298, SEQ ID NO: 308, SEQ ID NO: 398, SEQ ID NO: 408, SEQ ID NO: 418, SEQ ID NO: 428, SEQ ID NO: 438, SEQ ID NO: 448, SEQ ID NO: 458, SEQ ID NO: 468, SEQ ID NO: 478, SEQ ID NO: 488, SEQ ID NO: 498, and SEQ ID NO: 508.

13. The nucleic acid of claim 1, wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of: (a) a VH region as depicted in SEQ ID NO: 237, and a VL region as depicted in SEQ ID NO: 238; (b) a VH region as depicted in SEQ ID NO: 247, and a VL region as depicted in SEQ ID NO: 248; (c) a VH region as depicted in SEQ ID NO: 257, and a VL region as depicted in SEQ ID NO: 258; (d) a VH region as depicted in SEQ ID NO: 267, and a VL region as depicted in SEQ ID NO: 268; (e) a VH region as depicted in SEQ ID NO: 277, and a VL region as depicted in SEQ ID NO: 278; (f) a VH region as depicted in SEQ ID NO: 287, and a VL region as depicted in SEQ ID NO: 288; (g) a VH region as depicted in SEQ ID NO: 297, and a VL region as depicted in SEQ ID NO: 298; (h) a VH region as depicted in SEQ ID NO: 307, and a VL region as depicted in SEQ ID NO: 308; (i) a VH region as depicted in SEQ ID NO: 397, and a VL region as depicted in SEQ ID NO: 398; (k) a VH region as depicted in SEQ ID NO: 407, and a VL region as depicted in SEQ ID NO: 408; (l) a VH region as depicted in SEQ ID NO: 417, and a VL region as depicted in SEQ ID NO: 418; (m) a VH region as depicted in SEQ ID NO: 427, and a VL region as depicted in SEQ ID NO: 428; (n) a VH region as depicted in SEQ ID NO: 437, and a VL region as depicted in SEQ ID NO: 438; (o) a VH region as depicted in SEQ ID NO: 447, and a VL region as depicted in SEQ ID NO: 448; (p) a VH region as depicted in SEQ ID NO: 457, and a VL region as depicted in SEQ ID NO: 458; (q) a VH region as depicted in SEQ ID NO: 467, and a VL region as depicted in SEQ ID NO: 468; (r) a VH region as depicted in SEQ ID NO: 477, and a VL region as depicted in SEQ ID NO: 478; (s) a VH region as depicted in SEQ ID NO: 487, and a VL region as depicted in SEQ ID NO: 488; (t) a VH region as depicted in SEQ ID NO: 497, and a VL region as depicted in SEQ ID NO: 498; and (u) a VH region as depicted in SEQ ID NO: 507, and a VL region as depicted in SEQ ID NO: 508.

14. The nucleic acid of claim 13, wherein the first binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 239, SEQ ID NO: 249, SEQ ID NO: 259, SEQ ID NO: 269, SEQ ID NO: 279, SEQ ID NO: 289, SEQ ID NO: 299, SEQ ID NO: 309, SEQ ID NO: 399, SEQ ID NO: 409, SEQ ID NO: 419, SEQ ID NO: 429, SEQ ID NO: 439, SEQ ID NO: 449, SEQ ID NO: 459, SEQ ID NO: 469, SEQ ID NO: 479, SEQ ID NO: 489, SEQ ID NO: 499, and SEQ ID NO: 509.

15. The nucleic acid of claim 1 wherein the encoded binding molecule has an amino acid sequence shown in SEQ ID NO:300 or SEQ ID NO: 500.

Description

THE FIGURES SHOW

(1) FIG. 1:

(2) Sequence alignment of the extracellular domain (ECD) of human BCMA (amino acid residues 1-54 of the full-length protein) and murine BCMA (amino acid residues 1-49 of the full-length protein). Highlighted are the regions (domains or amino acid residues) which were exchanged in the chimeric constructs, as designated for the epitope clustering. Cysteines are depicted by black boxes. Disulfide bonds are indicated.

(3) FIGS. 2A and 2B:

(4) Epitope mapping of the BCMA constructs. Human and murine BCMA FIG. 2A as well as seven chimeric human-murine BCMA constructs FIG. 2B expressed on the surface of CHO cells as shown by flow cytometry. The expression of human BCMA on CHO was detected with a monoclonal anti-human BCMA antibody. Murine BCMA expression was detected with a monoclonal anti-murine BCMA-antibody. Bound monoclonal antibody was detected with an anti-rat IgG-Fc-gamma-specific antibody conjugated to phycoerythrin.

(5) FIG. 3A:

(6) Examples of binding molecules specific for epitope clusters E3 and E4, as detected in the epitope mapping of the chimeric BCMA constructs (see example A3). Some binding molecules are additionally capable of binding to the amino acid residue arginine at position 39 (E7) of human BCMA

(7) FIG. 3B:

(8) Example of a binding molecule specific for human and murine BCMA (see example B3)

(9) FIG. 3C:

(10) Example of a binding molecule specific for epitope clusters E1 and E4, as detected in the epitope mapping of the chimeric BCMA constructs (see example C3).

(11) FIG. 3D:

(12) Example of a binding molecule which binds to human BCMA, is not cross-reactive with murine BCMA and which additionally binds to the different chimeric BCMA constructs, as detected in the epitope mapping (see example D3).

(13) FIG. 4A:

(14) Determination of binding constants of bispecific binding molecules (anti BCMAanti CD3) on human and macaque BCMA using the Biacore system. Antigen was immobilized in low to intermediate density (100 RU) on CM5 chip. Dilutions of binders were floated over the chip surface and binding determined using BiaEval Software. Respective off-rates and the binding constant (KD) of the respective binders are depicted below every graph.

(15) FIG. 4B:

(16) Functionality and binding strength of affinity matured scFv molecules were analyzed in FACS using human BCMA transfected CHO cells. The results are depicted as FACS histograms of serial 1:3 dilutions of periplasmatic E. coli cell extracts, plotting the log of fluorescence intensity versus relative cell number.

(17) FIG. 4C:

(18) Functionality and binding strength of affinity matured scFv molecules were analyzed in FACS using human BCMA and macaque BCMA transfected CHO cells. The results are depicted as FACS histograms of serial 1:3 dilutions of periplasmatic E. coli cell extracts, plotting the log of fluorescence intensity versus relative cell number.

(19) FIG. 4D:

(20) Determination of binding constants of bispecific binding molecules (anti BCMAanti CD3) on human and macaque BCMA using the Biacore system. Antigen was immobilized in low to intermediate density (100 RU) on CM5 chip. Dilutions of binders were floated over the chip surface and binding determined using BiaEval Software. Respective off-rates and the binding constant (KD) of the respective binders are depicted below every graph.

(21) FIG. 5A:

(22) Cytotoxic activity of BCMA bispecific antibodies as measured in an 18-hour .sup.51chromium release assay. Effector cells: stimulated enriched human CD8 T cells. Target cells: Human BCMA transfected CHO cells (left figure) and macaque BCMA transfected CHO cells (right figure). Effector to target cell (E:T) ratio: 10:1.

(23) FIG. 5B:

(24) Cytotoxic activity of BCMA bispecific antibodies as measured in an 18-hour .sup.51chromium release assay. Effector cells: stimulated enriched human CD8 T cells. Target cells: Human BCMA transfected CHO cells (left figure) and macaque BCMA transfected CHO cells (right figure). Effector to target cell (E:T) ratio: 10:1.

(25) FIG. 6

(26) Determination of binding constants of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 on human and macaque BCMA and on human and macaque CD3 using the Biacore system. Antigen was immobilized in low to intermediate density (100-200 RU) on CM5 chip. Dilutions of bispecific antibodies were floated over the chip surface and binding determined using BiaEval Software. Respective on- and off-rates and the resulting binding constant (KD) of the respective bispecific antibodies are depicted below every graph.

(27) FIG. 7

(28) FACS analysis of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 on indicated cell lines: 1) human BCMA transfected CHO cells, 2) human CD3 positive human T cell line HBP-ALL, 3) macaque BCMA transfected CHO cells, 4) macaque T cell line 4119 LnPx, 5) BCMA-positive human multiple myeloma cell line NCI-H929 and 6) untransfected CHO cells. Negative controls [1) to 6)]: detection antibodies without prior BCMA/CD3 bispecific antibody.

(29) FIG. 8

(30) Scatchard analysis of BCMA/CD3 bispecific antibodies on BCMA-expressing cells. Cells were incubated with increasing concentrations of monomeric antibody until saturation. Antibodies were detected by flow cytometry. Values of triplicate measurements were plotted as hyperbolic curves and as sigmoid curves to demonstrate a valid concentration range used. Maximal binding was determined using Scatchard evaluation, and the respective KD values were calculated.

(31) FIG. 9

(32) Cytotoxic activity of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7, as measured in an 18-hour 51-chromium release assay against CHO cells transfected with human BCMA. Effector cells: stimulated enriched human CD8 T cells. Effector to target cell (E:T) ratio: 10:1.

(33) FIG. 10

(34) Cytotoxic activity of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 as measured in a 48-hour FACS-based cytotoxicity assay. Effector cells: unstimulated human PBMC. Target cells: CHO cells transfected with human BCMA. Effector to target cell (E:T)-ratio: 10:1.

(35) FIG. 11

(36) FACS analysis of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 on BAFF-R and TACI transfected CHO cells. Cell lines: 1) human BAFF-R transfected CHO cells, 2) human TACI transfected CHO cells 3) multiple myeloma cell line L363; negative controls: detection antibodies without prior BCMA/Cd3 bispecific antibody. Positive controls: BAFF-R detection: goat anti hu BAFF-R(R&D AF1162; 1:20) detected by anti-goat antibody-PE (Jackson 705-116-147; 1:50) TACI-detection: rabbit anti TACI antibody (abcam AB 79023; 1:100) detected by goat anti rabbit-antibody PE (Sigma P9757; 1:20).

(37) FIG. 12

(38) Cytotoxic activity of BCMA/CD3 bispecific antibodies as measured in an 18-hour 51-chromium release assay. Effector cells: stimulated enriched human CD8 T cells. Target cells: BCMA-positive human multiple myeloma cell line L363 (i.e. natural expresser). Effector to target cell (E:T) ratio: 10:1.

(39) FIG. 13

(40) Cytotoxic activity of BCMA/CD3 bispecific antibodies as measured in a 48-hour FACS-based cytotoxicity assay. Effector cells: unstimulated human PBMC. Target cells: human multiple myeloma cell line L363 (natural BCMA expresser). Effector to target cell (E:T)-ratio: 10:1.

(41) FIG. 14

(42) Cytotoxic activity of BCMA/CD3 bispecific antibodies as measured in a 48-hour FACS-based cytotoxicity assay. Effector cells: unstimulated human PBMC. Target cells: BCMA-positive human multiple myeloma cell line NCI-H929. Effector to target cell (E:T)-ratio: 10:1.

(43) FIG. 15

(44) Cytotoxic activity of BCMA/CD3 bispecific antibodies as measured in a 48-hour FACS-based cytotoxicity assay. Effector cells: macaque T cell line 4119LnPx. Target cells: CHO cells transfected with macaque BCMA. Effector to target cell (E:T) ratio: 10:1.

(45) FIG. 16:

(46) Anti-tumor activity of a BCMA/CD3 bispecific antibody of epitope cluster E3/E4E7 in an advanced-stage NCI-H929 xenograft model (see Example A16).

(47) FIG. 17:

(48) FACS-based cytotoxicity assay using human multiple myeloma cell lines NCI-H929, L-363 and OPM-2 as target cells and human PBMC as effector cells (48 h; E:T=10:1). The figure depicts the cytokine levels [pg/ml] which were determined for Il-2, IL-6, IL-10, TNF and IFN-gamma at increasing concentrations of a BCMA/CD3 bispecific antibody of epitope cluster E3/E4E7 (see Example A22).

EXAMPLES

(49) The following examples illustrate the invention. These examples should not be construed as to limit the scope of this invention. The examples are included for purposes of illustration, and the present invention is limited only by the claims.

Examples A

Example A1

Generation of CHO Cells Expressing Chimeric BCMA

(50) For the construction of the chimeric epitope mapping molecules, the amino acid sequence of the respective epitope domains or the single amino acid residue of human BCMA was changed to the murine sequence. The following molecules were constructed: Human BCMA ECD/E1 murine (SEQ ID NO: 1009)

(51) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 1 (amino acid residues 1-7 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 1-4 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 1-3 and G6Q mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E2 murine (SEQ ID NO: 1010)

(52) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 2 (amino acid residues 8-21 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 5-18 of SEQ ID NO: 1004 or 1008) S9F, Q10H, and N11S mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E3 murine (SEQ ID NO: 1011)

(53) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 3 (amino acid residues 24-41 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 21-36 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 31 and 32 and Q25H, S30N, L35A, and R39P mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E4 murine (SEQ ID NO: 1012)

(54) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 4 (amino acid residues 42-54 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 37-49 of SEQ ID NO: 1004 or 1008) N42D, A43P, N47S, N53Y and A54T mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E5 murine (SEQ ID NO: 1013)

(55) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 22 of SEQ ID NO: 1002 or 1007 (isoleucine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (lysine, position 19) I22K mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E6 murine (SEQ ID NO: 1014)

(56) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 25 of SEQ ID NO: 1002 or 1007 (glutamine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (histidine, position 22) Q25H mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E7 murine (SEQ ID NO: 1015)

(57) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 39 of SEQ ID NO: 1002 or 1007 (arginine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (proline, position 34) R39P mutation in SEQ ID NO: 1002 or 1007
A) The cDNA constructs were cloned into the mammalian expression vector pEF-DHFR and stably transfected into CHO cells. The expression of human BCMA on CHO cells was verified in a FACS assay using a monoclonal anti-human BCMA antibody. Murine BCMA expression was demonstrated with a monoclonal anti-mouse BCMA-antibody. The used concentration of the BCMA antibodies was 10 g/ml in PBS/2% FCS. Bound monoclonal antibodies were detected with an anti-rat-IgG-Fcy-PE (1:100 in PBS/2% FCS; Jackson-Immuno-Research #112-116-071). As negative control, cells were incubated with PBS/2% FCS instead of the first antibody. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6). The surface expression of human-murine BCMA chimeras, transfected CHO cells were analyzed and confirmed in a flow cytometry assay with different anti-BCMA antibodies (FIG. 2).
B) For the generation of CHO cells expressing human, macaque, mouse and human/mouse chimeric transmembrane BCMA, the coding sequences of human, macaque, mouse BCMA and the human-mouse BCMA chimeras (BCMA sequences as published in GenBank, accession numbers NM_001192 [human]; NM_011608 [mouse] and XM_001106892 [macaque]) were obtained by gene synthesis according to standard protocols. The gene synthesis fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs and the coding sequence of a 19 amino acid immunoglobulin leader peptide, followed in frame by the coding sequence of the BCMA proteins respectively in case of the chimeras with the respective epitope domains of the human sequence exchanged for the murine sequence.

(58) Except for the human BCMA ECD/E4 murine and human BCMA constructs the coding sequence of the extracellular domain of the BCMA proteins was followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker followed by the intracellular domain of human EpCAM (amino acids 226-314; sequence as published in GenBank accession number NM_002354).

(59) All coding sequences were followed by a stop codon. The gene synthesis fragments were also designed as to introduce suitable restriction sites. The gene synthesis fragments were cloned into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). All aforementioned procedures were carried out according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y. (2001)). For each antigen a clone with sequence-verified nucleotide sequence was transfected into DHFR deficient CHO cells for eukaryotic expression of the constructs. Eukaryotic protein expression in DHFR deficient CHO cells was performed as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566. Gene amplification of the constructs was induced by increasing concentrations of methotrexate (MTX) to a final concentration of up to 20 nM MTX.

Example A2

2.1 Transient Expression in HEK 293 Cells

(60) Clones of the expression plasmids with sequence-verified nucleotide sequences were used for transfection and protein expression in the FreeStyle 293 Expression System (Invitrogen GmbH, Karlsruhe, Germany) according to the manufacturer's protocol. Supernatants containing the expressed proteins were obtained, cells were removed by centrifugation and the supernatants were stored at 20 C.

2.2 Stable Expression in CHO Cells

(61) Clones of the expression plasmids with sequence-verified nucleotide sequences were transfected into DHFR deficient CHO cells for eukaryotic expression of the constructs. Eukaryotic protein expression in DHFR deficient CHO cells was performed as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566. Gene amplification of the constructs was induced by increasing concentrations of methotrexate (MTX) to a final concentration of 20 nM MTX. After two passages of stationary culture the cells were grown in roller bottles with nucleoside-free HyQ PF CHO liquid soy medium (with 4.0 mM L-Glutamine with 0.1% Pluronic F-68; HyClone) for 7 days before harvest. The cells were removed by centrifugation and the supernatant containing the expressed protein was stored at 20 C.

2.3 Protein Purification

(62) Purification of soluble BCMA proteins was performed as follows: kta Explorer System (GE Healthcare) and Unicorn Software were used for chromatography. Immobilized metal affinity chromatography (IMAC) was performed using a Fractogel EMD Chelate (Merck) which was loaded with ZnCl2 according to the protocol provided by the manufacturer. The column was equilibrated with buffer A (20 mM sodium phosphate buffer pH 7.2, 0.1 M NaCl) and the filtrated (0.2 m) cell culture supernatant was applied to the column (10 ml) at a flow rate of 3 ml/min. The column was washed with buffer A to remove unbound sample. Bound protein was eluted using a two-step gradient of buffer B (20 mM sodium phosphate buffer pH 7.2, 0.1 M NaCl, 0.5 M imidazole) according to the following procedure:

(63) Step 1: 10% buffer B in 6 column volumes

(64) Step 2: 100% buffer B in 6 column volumes

(65) Eluted protein fractions from step 2 were pooled for further purification. All chemicals were of research grade and purchased from Sigma (Deisenhofen) or Merck (Darmstadt).

(66) Gel filtration chromatography was performed on a HiLoad 16/60 Superdex 200 prep grade column (GE/Amersham) equilibrated with Equi-buffer (10 mM citrate, 25 mM lysine-HCl, pH 7.2 for proteins expressed in HEK cells and PBS pH 7.4 for proteins expressed in CHO cells). Eluted protein samples (flow rate 1 ml/min) were subjected to standard SDS-PAGE and Western Blot for detection. Protein concentrations were determined using OD280 nm.

(67) Proteins obtained via transient expression in HEK 293 cells were used for immunizations. Proteins obtained via stable expression in CHO cells were used for selection of binders and for measurement of binding.

Example A3

Epitope Clustering of Murine scFv-Fragments

(68) Cells transfected with human or murine BCMA, or with chimeric BCMA molecules were stained with crude, undiluted periplasmic extract containing scFv binding to human/macaque BCMA. Bound scFv were detected with 1 g/ml of an anti-FLAG antibody (Sigma F1804) and a R-PE-labeled anti-mouse Fc gamma-specific antibody (1:100; Dianova #115-116-071). All antibodies were diluted in PBS with 2% FCS. As negative control, cells were incubated with PBS/2% FCS instead of the periplasmic extract. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6).

Example A4

Procurement of Different Recombinant Forms of Soluble Human and Macaque BCMA

(69) A) The coding sequences of human and rhesus BCMA (as published in GenBank, accession numbers NM_001192 [human], XM_001106892 [rhesus]) coding sequences of human albumin, human Fc1 and murine albumin were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of human and macaque BCMA respectively and human albumin, human IgG1 Fc and murine albumin respectively as well as soluble proteins comprising only the extracellular domains of BCMA. To generate the constructs for expression of the soluble human and macaque BCMA proteins, cDNA fragments were obtained by PCR mutagenesis of the full-length BCMA cDNAs described above and molecular cloning according to standard protocols.

(70) For the fusions with human albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and rhesus BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of human serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(71) For the fusions with murine IgG1, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of the hinge and Fc gamma portion of human IgG1, followed in frame by the coding sequence of a hexahistidine tag and a stop codon.

(72) For the fusions with murine albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of murine serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(73) For the soluble extracellular domain constructs, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly1-linker, followed in frame by the coding sequence of a FLAG tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(74) The cDNA fragments were also designed to introduce restriction sites at the beginning and at the end of the fragments. The introduced restriction sites, EcoRI at the 5 end and SalI at the 3 end, were utilized in the following cloning procedures. The cDNA fragments were cloned via EcoRI and SalI into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). The aforementioned procedures were all carried out according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y. (2001)).

(75) B) The coding sequences of human and macaque BCMA as described above and coding sequences of human albumin, human Fc1, murine Fc1, murine Fc2a, murine albumin, rat albumin, rat Fc1 and rat Fc2b were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of human and macaque BCMA respectively and human albumin, human IgG1 Fc, murine IgG1 Fc, murine IgG2a Fc, murine albumin, rat IgG1 Fc, rat IgG2b and rat albumin respectively as well as soluble proteins comprising only the extracellular domains of BCMA. To generate the constructs for expression of the soluble human and macaque BCMA proteins cDNA fragments were obtained by PCR mutagenesis of the full-length BCMA cDNAs described above and molecular cloning according to standard protocols. For the fusions with albumins the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs and the coding sequence of a 19 amino acid immunoglobulin leader peptide, followed in frame by the coding sequence of the extracellular domain of the respective BCMA protein followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of the respective serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(76) For the fusions with IgG Fcs the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs and the coding sequence of a 19 amino acid immunoglobulin leader peptide, followed in frame by the coding sequence of the extracellular domain of the respective BCMA protein followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, except for human IgG1 Fc where an artificial Ser1-Gly1-linker was used, followed in frame by the coding sequence of the hinge and Fc gamma portion of the respective IgG, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon. For the soluble extracellular domain constructs the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs and the coding sequence of a 19 amino acid immunoglobulin leader peptide, followed in frame by the coding sequence of the extracellular domain of the respective BCMA protein followed in frame by the coding sequence of an artificial Ser1-Gly1-linker, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(77) For cloning of the constructs suitable restriction sites were introduced. The cDNA fragments were all cloned into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. 2001). The aforementioned procedures were all carried out according to standard protocols (Sambrook, 2001).

(78) The following constructs were designed to enable directed panning on distinct epitopes. The coding sequence of murine-human BCMA chimeras and murine-macaque BCMA chimeras (mouse, human and macaque BCMA sequences as described above) and coding sequences of murine albumin and murine Fc1 were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of murine-human and murine-macaque BCMA chimeras respectively and murine IgG1 Fc and murine albumin, respectively. To generate the constructs for expression of the soluble murine-human and murine-macaque BCMA chimeras cDNA fragments of murine BCMA (amino acid 1-49) with the respective epitope domains mutated to the human and macaque sequence respectively were obtained by gene synthesis according to standard protocols. Cloning of constructs was carried out as described above and according to standard protocols (Sambrook, 2001).

(79) The following molecules were constructed: amino acid 1-4 human, murine IgG1 Fc amino acid 1-4 human, murine albumin amino acid 1-4 rhesus, murine IgG1 Fc amino acid 1-4 rhesus, murine albumin amino acid 5-18 human, murine IgG1 Fc amino acid 5-18 human, murine albumin amino acid 5-18 rhesus, murine IgG1 Fc amino acid 5-18 rhesus, murine albumin amino acid 37-49 human, murine IgG1 Fc amino acid 37-49 human, murine albumin amino acid 37-49 rhesus, murine IgG1 Fc amino acid 37-49 rhesus, murine albumin

Example A5

5.1 Biacore-Based Determination of Bispecific Antibody Affinity to Human and Macaque BCMA and CD3

(80) Biacore analysis experiments were performed using recombinant BCMA fusion proteins with human serum albumin (ALB) to determine BCMA target binding. For CD3 affinity measurements, recombinant fusion proteins having the N-terminal 27 amino acids of the CD3 epsilon (CD3e) fused to human antibody Fc portion were used. This recombinant protein exists in a human CD3e1-27 version and in a cynomolgous CD3e version, both bearing the epitope of the CD3 binder in the bispecific antibodies.

(81) In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 100 to 150 RU of the respective recombinant antigen using acetate buffer pH4.5 according to the manufacturer's manual. The bispecific antibody samples were loaded in five concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP running buffer (GE Healthcare). Flow rate was 30 to 35 l/min for 3 min, then HBS-EP running buffer was applied for 8 min again at a flow rate of 30 to 35 l/ml. Regeneration of the chip was performed using 10 mM glycine 0.5 M NaCl pH 2.45. Data sets were analyzed using BiaEval Software (see FIG. A 4). In general two independent experiments were performed.

5.2 Binding Affinity to Human and Macaque BCMA

(82) Binding affinities of BCMA/CD3 bispecific antibodies to human and macaque BCMA were determined by Biacore analysis using recombinant BCMA fusion proteins with mouse albumin (ALB).

(83) In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 150 to 200 RU of the respective recombinant antigen using acetate buffer pH4.5 according to the manufacturer's manual. The bispecific antibody samples were loaded in five concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP running buffer (GE Healthcare). For BCMA affinity determinations the flow rate was 35 l/min for 3 min, then HBS-EP running buffer was applied for 10, 30 or 60 min again at a flow rate of 35 l/ml. Regeneration of the chip was performed using a buffer consisting of a 1:1 mixture of 10 mM glycine 0.5 M NaCl pH 1.5 and 6 M guanidine chloride solution. Data sets were analyzed using BiaEval Software (see FIG. A 6). In general two independent experiments were performed.

(84) Confirmative human and macaque CD3 epsilon binding was performed in single experiments using the same concentrations as applied for BCMA binding; off-rate determination was done for 10 min dissociation time.

(85) All BCMA/CD3 bispecific antibodies according to the invention, i.e. those of epitope cluster E3/E4E7, showed high affinities to human BCMA in the subnanomolar range. Binding to macaque BCMA was balanced, also showing affinities in the subnanomolar range. Affinities and affinity gaps of BCMA/CD3 bispecific antibodies are shown in Table 2.

(86) TABLE-US-00002 TABLE 2 Affinities of BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4 E7 to human and macaque BCMA as determined by Biacore analysis, and calculated affinity gaps (ma BCMA:hu BCMA). BCMA/CD3 hu ma bispecific BCMA BCMA Affinity gap antibody [nM] [nM] ma BCMA:hu BCMA BCMA-24 0.11 0.18 1.6 BCMA-30 0.21 0.20 1:1.1 BCMA-28 0.18 0.21 1.2 BCMA-25 0.29 0.30 1.0 BCMA-27 0.25 0.12 1:2.1 BCMA-31 0.24 0.35 1.5 BCMA-29 0.34 0.27 1:1.3 BCMA-43 0.50 0.29 1:1.7 BCMA-40 0.67 0.25 1:2.7 BCMA-49 0.37 0.29 1:1.3 BCMA-44 0.17 0.095 1:1.8 BCMA-41 0.32 0.15 1:2.1 BCMA-47 0.24 0.092 1:2.6 BCMA-50 0.35 0.15 1:2.3 BCMA-45 0.43 0.15 1:2.9 BCMA-42 0.37 0.11 1:3.4 BCMA-48 0.46 0.11 1:4.2 BCMA-51 0.41 0.20 1:2.1

5.3 Biacore-Based Determination of the Bispecific Antibody Affinity to Human and Macaque BCMA

(87) The affinities of BCMA/CD3 bispecific antibodies to recombinant soluble BCMA on CM5 chips in Biacore measurements were repeated to reconfirm KDs and especially off-rates using longer dissociation periods (60 min instead of 10 min as used in the previous experiment). All of the tested BCMA/CD3 bispecific antibodies underwent two independent affinity measurements with five different concentrations each.

(88) The affinities of the BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 were clearly subnanomolar, see examples in Table 3.

(89) TABLE-US-00003 TABLE 3 Affinities (KD) of BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4 E7 from Biacore experiments using extended dissociation times (two independent experiments each). BCMA/CD3 KD [nM] KD [nM] bispecific antibody human BCMA macaque BCMA BCMA-30 0.302 0.074 0.284 0.047 BCMA-50 0.514 0.005 0.196 0.012

Example A6

Bispecific Binding and Interspecies Cross-Reactivity

(90) For confirmation of binding to human and macaque BCMA and CD3, bispecific antibodies were tested by flow cytometry using CHO cells transfected with human and macaque BCMA, respectively, the human multiple myeloma cell line NCI-H929 expressing native human BCMA, CD3-expressing human T cell leukemia cell line HPB-ALL (DSMZ, Braunschweig, ACC483) and the CD3-expressing macaque T cell line 4119LnPx (Knappe A, et al., Blood, 2000, 95, 3256-3261). Moreover, untransfected CHO cells were used as negative control.

(91) For flow cytometry 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific antibody at a concentration of 5 g/ml. The cells were washed twice in PBS/2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS/2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS/2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(92) The BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 stained CHO cells transfected with human and macaque BCMA, the human BCMA-expressing multiple myeloma cell line NCI-H929 as well as human and macaque T cells. Moreover, there was no staining of untransfected CHO cells (see FIG. A 7).

Example A7

Scatchard-Based Determination of Bispecific-Antibody Affinity to Human and Macaque BCMA

(93) For Scatchard analysis, saturation binding experiments are performed using a monovalent detection system developed at Micromet (anti-His Fab/Alexa 488) to precisely determine monovalent binding of the bispecific antibodies to the respective cell line.

(94) 210.sup.4 cells of the respective cell line (recombinantly human BCMA-expressing CHO cell line, recombinantly macaque BCMA-expressing CHO cell line) are incubated with each 50 l of a triplet dilution series (eight dilutions at 1:2) of the respective BCMA bispecific antibody starting at 100 nM followed by 16 h incubation at 4 C. under agitation and one residual washing step. Then, the cells are incubated for further 30 min with 30 l of an anti-His Fab/Alexa488 solution (Micromet; 30 g/ml). After one washing step, the cells are resuspended in 150 l FACS buffer containing 3.5% formaldehyde, incubated for further 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS Cantoll machine and FACS Diva software. Data are generated from two independent sets of experiments. Values are plotted as hyperbole binding curves. Respective Scatchard analysis is calculated to extrapolate maximal binding (Bmax). The concentrations of bispecific antibodies at half-maximal binding are determined reflecting the respective KDs. Values of triplicate measurements are plotted as hyperbolic curves. Maximal binding is determined using Scatchard evaluation and the respective KDs are calculated.

(95) The affinities of BCMA/CD3 bispecific antibodies to CHO cells transfected with human or macaque BCMA were determined by Scatchard analysis as the most reliable method for measuring potential affinity gaps between human and macaque BCMA.

(96) Cells expressing the BCMA antigen were incubated with increasing concentrations of the respective monomeric BCMA/CD3 bispecific antibody until saturation was reached (16 h). Bound bispecific antibody was detected by flow cytometry. The concentrations of BCMA/CD3 bispecific antibodies at half-maximal binding were determined reflecting the respective KDs.

(97) Values of triplicate measurements were plotted as hyperbolic curves and as S-shaped curves to demonstrate proper concentration ranges from minimal to optimal binding. Maximal binding (Bmax) was determined (FIG. A 8) using Scatchard evaluation and the respective KDs were calculated. Values depicted in Table 4 were derived from two independent experiments per BCMA/CD3 bispecific antibody.

(98) Cell based Scatchard analysis confirmed that the BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 are subnanomolar in affinity to human BCMA and present with a small interspecies BCMA affinity gap of 1.9-2.9.

(99) Another group of antibodies was identified during epitope clustering (see Examples A1 and A2), which is capable of binding to epitope clusters 1 and 4 of BCMA (E1/E4). Epitope cluster 1 is MLQMAGQ (SEQ ID NO: 1018) and epitope cluster 4 is NASVTNSVKGTNA (SEQ ID NO: 1019). In contrast to the BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7, antibodies of the epitope cluster E1/E4 show a higher affinity gap between human and macaque BCMA of 3.9-4.5.

(100) TABLE-US-00004 TABLE 4 Affinities (KD) of BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4 E7 from cell based Scatchard analysis (two independent experiments each) with the calculated affinity gap KD macaque BCMA/KD human BCMA. BCMA/CD3 KD [nM] KD [nM] x-fold KD difference bispecific human macaque KD ma vs. antibody BCMA BCMA KD hu BCMA BCMA-30 0.85 0.07 2.50 1.12 2.9 BCMA-50 0.93 0.08 1.75 0.62 1.9

Example A8

Cytotoxic Activity

8.1 Chromium Release Assay with Stimulated Human T Cells

(101) Stimulated T cells enriched for CD8+ T cells were obtained as follows: A petri dish (145 mm diameter, Greiner bio-one GmbH, Kremsmunster) was coated with a commercially available anti-CD3 specific antibody (OKT3, Orthoclone) in a final concentration of 1 g/ml for 1 hour at 37 C. Unbound protein was removed by one washing step with PBS. 3-510.sup.7 human PBMC were added to the precoated petri dish in 120 ml of RPMI 1640 with stabilized glutamine/10% FCS/IL-2 20 U/ml (Proleukin, Chiron) and stimulated for 2 days. On the third day, the cells were collected and washed once with RPMI 1640. IL-2 was added to a final concentration of 20 U/ml and the cells were cultured again for one day in the same cell culture medium as above. CD8+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4+ T cells and CD56+ NK cells using Dynal-Beads according to the manufacturer's protocol.

(102) Macaque or human BCMA-transfected CHO target cells (BCMA-positive target cells) were washed twice with PBS and labeled with 11.1 MBq .sup.51Cr in a final volume of 100 l RPMI with 50% FCS for 60 minutes at 37 C. Subsequently, the labeled target cells were washed 3 times with 5 ml RPMI and then used in the cytotoxicity assay. The assay was performed in a 96-well plate in a total volume of 200 l supplemented RPMI with an E:T ratio of 10:1. A starting concentration of 0.01-1 g/ml of purified bispecific antibody and threefold dilutions thereof were used. Incubation time for the assay was 18 hours. Cytotoxicity was determined as relative values of released chromium in the supernatant relative to the difference of maximum lysis (addition of Triton-X) and spontaneous lysis (without effector cells). All measurements were carried out in quadruplicates. Measurement of chromium activity in the supernatants was performed in a Wizard 3 gamma counter (Perkin Elmer Life Sciences GmbH, Kln, Germany). Analysis of the experimental data was carried out with Prism 5 for Windows (version 5.0, GraphPad Software Inc., San Diego, Calif., USA). EC50 values calculated by the analysis program from the sigmoidal dose response curves were used for comparison of cytotoxic activity (see FIG. A 5).

8.2 Potency of Redirecting Stimulated Human Effector T Cells Against Human BCMA-Transfected CHO Cells

(103) The cytotoxic activity of BCMA/CD3 bispecific antibodies was analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using CHO cells transfected with human BCMA as target cells, and stimulated enriched human CD8 T cells as effector cells. The experiment was carried out as described in Example A8.1.

(104) All BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 showed potent cytotoxic activity against human BCMA transfected CHO cells with EC50-values in a range between 1-digit pg/ml and low 2-digit pg/ml (FIG. A9 and Table 5). So the epitope cluster E3/E4E7 presents with a very favorable epitope-activity relationship supporting very potent bispecific antibody mediated cytotoxic activity.

(105) TABLE-US-00005 TABLE 5 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies antibodies of the epitope cluster E3/E4 E7 analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using CHO cells transfected with human BCMA as target cells, and stimulated enriched human CD8 T cells as effector cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value BCMA-24 4.6 0.91 BCMA-30 6 0.83 BCMA-28 5.7 0.90 BCMA-25 9.7 0.87 BCMA-27 5.4 0.90 BCMA-31 11 0.89 BCMA-29 9 0.89 BCMA-43 12 0.74 BCMA-40 15 0.77 BCMA-49 22 0.76 BCMA-44 13 0.78 BCMA-41 9.9 0.76 BCMA-47 8.0 0.80 BCMA-50 18 0.77 BCMA-45 14 0.81 BCMA-42 22 0.83 BCMA-48 31 0.76 BCMA-51 30 0.83

8.3 FACS-Based Cytotoxicity Assay with Unstimulated Human PBMC

(106) Isolation of Effector Cells

(107) Human peripheral blood mononuclear cells (PBMC) were prepared by Ficoll density gradient centrifugation from enriched lymphocyte preparations (buffy coats), a side product of blood banks collecting blood for transfusions. Buffy coats were supplied by a local blood bank and PBMC were prepared on the same day of blood collection. After Ficoll density centrifugation and extensive washes with Dulbecco's PBS (Gibco), remaining erythrocytes were removed from PBMC via incubation with erythrocyte lysis buffer (155 mM NH.sub.4Cl, 10 mM KHCO.sub.3, 100 M EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100g. Remaining lymphocytes mainly encompass B and T lymphocytes, NK cells and monocytes. PBMC were kept in culture at 37 C./5% CO.sub.2 in RPMI medium (Gibco) with 10% FCS (Gibco).

(108) Depletion of CD14.sup.+ and CD56.sup.+ Cells

(109) For depletion of CD14.sup.+ cells, human CD14 MicroBeads (Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted and centrifuged for 10 min at room temperature with 300g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 l/10.sup.7 cells; PBS (Invitrogen, #20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA (Sigma-Aldrich, #E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20 l/10.sup.7 cells) were added and incubated for 15 min at 4-8 C. The cells were washed with MACS isolation buffer (1-2 ml/10.sup.7 cells). After centrifugation (see above), supernatant was discarded and cells resuspended in MACS isolation buffer (500 l/10.sup.8 cells). CD14/CD56 negative cells were then isolated using LS Columns (Miltenyi Biotec, #130-042-401). PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium i.e. RPMI1640 (Biochrom AG, #FG1215) supplemented with 10% FBS (Biochrom AG, #S0115), 1 non-essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, #L1613), 1 mM sodium pyruvate (Biochrom AG, #L0473) and 100 U/ml penicillin/streptomycin (Biochrom AG, #A2213) at 37 C. in an incubator until needed.

(110) Target Cell Labeling

(111) For the analysis of cell lysis in flow cytometry assays, the fluorescent membrane dye DiOC.sub.18 (DiO) (Molecular Probes, #V22886) was used to label human BCMA- or macaque BCMA-transfected CHO cells as target cells (human/macaque BCMA-positive target cells) and distinguish them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10.sup.6 cells/ml in PBS containing 2% (v/v) FBS and the membrane dye DiO (5 l/10.sup.6 cells). After incubation for 3 min at 37 C., cells were washed twice in complete RPMI medium and the cell number adjusted to 1.2510.sup.5 cells/ml. The vitality of cells was determined using 0.5% (v/v) isotonic EosinG solution (Roth, #45380).

(112) Flow Cytometry Based Analysis

(113) This assay was designed to quantify the lysis of macaque or human BCMA-transfected CHO cells (or BCMA positive target cells) in the presence of serial dilutions of BCMA/CD3 bispecific antibodies. Equal volumes of DiO-labeled target cells and effector cells (i.e., PBMC w/o CD14.sup.+ cells) were mixed, resulting in an E:T cell ratio of 10:1. 160 l of this suspension were transferred to each well of a 96-well plate. 40 l of serial dilutions of the BCMA/CD3 bispecific antibodies and a negative control bispecific antibody (a CD3 based bispecific antibody recognizing an irrelevant target antigen) or RPMI complete medium as an additional negative control were added. The cytotoxic reaction mediated by the BCMA/CD3 bispecific antibodies proceeded for 48 hours in a 7% CO.sub.2 humidified incubator. Then cells were transferred to a new 96-well plate, and loss of target cell membrane integrity was monitored by adding propidium iodide (PI) at a final concentration of 1 g/ml. PI is a membrane impermeable dye that normally is excluded from viable cells, whereas dead cells take it up and become identifiable by fluorescent emission. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson). Target cells were identified as DiO-positive cells. PI-negative target cells were classified as living target cells. Percentage of cytotoxicity was calculated according to the following formula:
Cytotoxicity [%]=n(dead target cells)100/n(target cells)
n=number of events

(114) Using GraphPad Prism 5 software (Graph Pad Software, San Diego), the percentage of cytotoxicity was plotted against the corresponding bispecific antibody concentrations. Dose response curves were analyzed with the four parametric logistic regression models for evaluation of sigmoid dose response curves with fixed hill slope and EC50 values were calculated.

8.4 Unstimulated Human PBMC Against Human BCMA-Transfected Target Cells

(115) The cytotoxic activity of BCMA/CD3 bispecific antibodies was analyzed in a FACS-based cytotoxicity assay using CHO cells transfected with human BCMA as target cells, and unstimulated human PBMC as effector cells. The assay was carried out as described above (Example A8.3).

(116) The results of the FACS-based cytotoxicity assays with unstimulated human PBMC as effector cells and human BCMA-transfected CHO cells as targets are shown in FIG. A10 and Table 6.

(117) TABLE-US-00006 TABLE 6 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies of epitope cluster E3/E4 E7 as measured in a 48-hour FACS-based cytotoxicity assay with unstimulated human PBMC as effector cells and CHO cells transfected with human BCMA as target cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value BCMA-30 314 0.98 BCMA-50 264 0.97

Example A9

9.1 Exclusion of Cross-Reactivity with BAFF-Receptor

(118) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(119) The bispecific binders were shown to not be cross-reactive with BAFF receptor.

9.2 Exclusion of BCMA/CD3 Bispecific Antibody Cross-Reactivity with Human BAFF-Receptor (BAFF-R) and TACI

(120) For exclusion of binding to human BAFF-R and TACI, BCMA/CD3 bispecific antibodies were tested by flow cytometry using CHO cells transfected with human BAFF-R and TACI, respectively. Moreover, L363 multiple myeloma cells were used as positive control for binding to human BCMA. Expression of BAFF-R and TACI antigen on CHO cells was confirmed by two positive control antibodies. Flow cytometry was performed as described in the previous example.

(121) Flow cytometric analysis confirmed that none of the BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 cross-reacts with human BAFF-R or human TACI (see FIG. A11).

Example A10

Cytotoxic Activity

(122) The potency of human-like BCMA bispecific antibodies in redirecting effector T cells against BCMA-expressing target cells is analyzed in five additional in vitro cytotoxicity assays:

(123) 1. The potency of BCMA bispecific antibodies in redirecting stimulated human effector T cells against a BCMA-positive (human) tumor cell line is measured in a 51-chromium release assay.

(124) 2. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against human BCMA-transfected CHO cells is measured in a FACS-based cytotoxicity assay.

(125) 3. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against a BCMA-positive (human) tumor cell line is measured in a FACS-based cytotoxicity assay.

(126) 4. For confirmation that the cross-reactive BCMA bispecific antibodies are capable of redirecting macaque T cells against macaque BCMA-transfected CHO cells, a FACS-based cytotoxicity assay is performed with a macaque T cell line as effector T cells.

(127) 5. The potency gap between monomeric and dimeric forms of BCMA bispecific antibodies is determined in a 51-chromium release assay using human BCMA-transfected CHO cells as target cells and stimulated human T cells as effector cells.

Example A11

Stimulated Human T Cells Against the BCMA-Positive Human Multiple Myeloma Cell Line L363

(128) The cytotoxic activity of BCMA/CD3 bispecific antibodies was analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using the BCMA-positive human multiple myeloma cell line L363 (DSMZ No. ACC49) as source of target cells, and stimulated enriched human CD8 T cells as effector cells. The assay was carried out as described in Example A8.1.

(129) In accordance with the results of the 51-chromium release assays with stimulated enriched human CD8 T lymphocytes as effector cells and human BCMA-transfected CHO cells as targets, BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7 are potent in cytotoxic activity (FIG. A12 and Table 7).

(130) Unexpectedly, however, BCMA/CD3 bispecific antibodies of epitope cluster E1/E4although potent in cytotoxic activity against CHO cell transfected with human BCMAproved to be rather weakly cytotoxic against the human multiple myeloma cell line L363 expressing native BCMA at low density on the cell surface (FIG. A12 and Table 7). Without wishing to be bound by theory, the inventors believe that the E1/E4 epitope of human BCMA might be less well accessible on natural BCMA expressers than on BCMA-transfected cells.

(131) TABLE-US-00007 TABLE 7 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies of epitope clusters E1/E4 (rows 1 and 2) and E3/E4 E7 (rows 3 and 4) analyzed in an 18-hour 51-chromium (.sup.51Cr) release cytotoxicity assay with the BCMA-positive human multiple myeloma cell line L363 as source of target cells, and stimulated enriched human CD8 T cells as effector cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value 1 BCMA-54 685 0.84 2 BCMA-53 1107 0.82 3 BCMA-30 182 0.83 4 BCMA-50 148 0.83

Example A12

Unstimulated Human PBMC Against the BCMA-Positive Human Multiple Myeloma Cell Line L363

(132) The cytotoxic activity of BCMA/CD3 bispecific antibodies was furthermore analyzed in a FACS-based cytotoxicity assay using the BCMA-positive human multiple myeloma cell line L363 (DSMZ, ACC49)showing the weakest surface expression of native BCMA of all tested target T cell linesas source of target cells and unstimulated human PBMC as effector cells. The assay was carried out as described above (Example A8.3).

(133) As observed in the 51-chromium release assay with stimulated enriched human CD8 T lymphocytes against the human multiple myeloma cell line L363, the BCMA/CD3 bispecific antibodies of epitope cluster E1/E4in contrast to their potent cytotoxic activity against CHO cell transfected with human BCMAproved to be again less potent in redirecting the cytotoxic activity of unstimulated PBMC against the human multiple myeloma cell line L363 expressing native BCMA at low density on the cell surface. This is in line with the theory provided hereinabove, i.e., the E1/E4 epitope of human BCMA may be less well accessible on natural BCMA expressers than on BCMA-transfected cells. BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 presented with 3-digit pg/ml EC50-values in this assay (see FIG. A13 and Table 8).

(134) TABLE-US-00008 TABLE 8 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies of epitope clusters E1/E4 (rows 1 and 2) and E3/E4 E7 (rows 3 and 4) as measured in a 48-hour FACS-based cytotoxicity assay with unstimulated human PBMC as effector cells and the human multiple myeloma cell line L363 as source of target cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value 1 BCMA-54 3162 0.99 2 BCMA-53 2284 0.98 3 BCMA-30 589 0.99 4 BCMA-50 305 0.99

(135) Expectedly, EC50-values were higher in cytotoxicity assays with unstimulated PBMC as effector cells than in cytotoxicity assays using enriched stimulated human CD8 T cells.

Example A13

Unstimulated Human PBMC Against the BCMA-Positive Human Multiple Myeloma Cell Line NCI-H929

(136) The cytotoxic activity of BCMA/CD3 bispecific antibodies was analyzed in a FACS-based cytotoxicity assay using the BCMA-positive human multiple myeloma cell line NCI-H929 (ATCC CRL-9068) as source of target cells and unstimulated human PBMC as effector cells. The assay was carried out as described above (Example A8.3).

(137) The results of this assay with another human multiple myeloma cell line (i.e. NCI-H929) expressing native BCMA on the cell surface confirm those obtained with human multiple myeloma cell line L363. Again, BCMA/CD3 bispecific antibodies of epitope cluster E1/E4in contrast to their potent cytotoxic activity against CHO cell transfected with human BCMAproved to be less potent in redirecting the cytotoxic activity of unstimulated PBMC against human multiple myeloma cells confirming the theory that the E1/E4 epitope of human BCMA may be less well accessible on natural BCMA expressers than on BCMA-transfected cells. Such an activity gap between BCMA-transfected target cells and natural expressers as seen for the E1/E4 binders was not found for the E3/E4E7 binders. BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 presented with 2-digit pg/ml EC50-values and hence redirected unstimulated PBMC against NCI-H929 target cells with surprisingly good EC50-values (see FIG. A14 and Table 9).

(138) TABLE-US-00009 TABLE 9 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies of epitope clusters E1/E4 (rows 1 and 2) and E3/E4 E7 (rows 3 and 4) as measured in a 48-hour FACS-based cytotoxicity assay with unstimulated human PBMC as effector cells and the human multiple myeloma cell line NCI-H929 as source of target cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value 1 BCMA-54 2604 0.99 2 BCMA-53 2474 0.99 3 BCMA-30 38.0 0.95 4 BCMA-50 40.4 0.97

(139) As expected, EC50-values were lower with the human multiple myeloma cell line NCI-H929, which expresses higher levels of BCMA on the cell surface compared to L363.

Example A14

Macaque T Cells Against Macaque BCMA-Expressing Target Cells

(140) Finally, the cytotoxic activity of BCMA/CD3 bispecific antibodies was analyzed in a FACS-based cytotoxicity assay using CHO cells transfected with macaque BCMA as target cells, and a macaque T cell line as source of effector cells.

(141) The macaque T cell line 4119LnPx (Knappe et al. Blood 95:3256-61 (2000)) was used as source of effector cells. Target cell labeling of macaque BCMA-transfected CHO cells and flow cytometry based analysis of cytotoxic activity was performed as described above.

(142) Macaque T cells from cell line 4119LnPx were induced to efficiently kill macaque BCMA-transfected CHO cells by BCMA/CD3 bispecific antibodies of epitope cluster E3/E4E7. The antibodies presented very potently with 1-digit pg/ml EC50-values in this assay, confirming that these antibodies are very active in the macaque system. On the other hand, BCMA/CD3 bispecific antibodies of the epitope cluster E1/E4 showed a significantly weaker potency with EC50-values in the 2-digit to 3-digit pg/ml range (see FIG. A15 and Table 10). The E3/E4E7 specific antibodies are hence about 20 to over 100 times more potent in the macaque system.

(143) TABLE-US-00010 TABLE 10 EC50 values [pg/ml] of BCMA/CD3 bispecific antibodies of epitope clusters E1/E4 (rows 1 and 2) and E3/E4 E7 (rows 3 and 4) as measured in a 48-hour FACS-based cytotoxicity assay with macaque T cell line 4119LnPx as effector cells and CHO cells transfected with macaque BCMA as target cells. BCMA/CD3 R bispecific EC50 square antibody [pg/ml] value 1 BCMA-54 78.5 0.98 2 BCMA-53 183 0.96 3 BCMA-30 1.7 0.97 4 BCMA-50 3.7 0.96

Example A15

Potency Gap Between BCMA/CD3 Bispecific Antibody Monomer and Dimer

(144) In order to determine the difference in cytotoxic activity between the monomeric and the dimeric isoform of individual BCMA/CD3 bispecific antibodies (referred to as potency gap), a 51-chromium release cytotoxicity assay as described hereinabove (Example A8.1) was carried out with purified BCMA/CD3 bispecific antibody monomer and dimer. The potency gap was calculated as ratio between EC50 values of the bispecific antibody's monomer and dimer. Potency gaps of the tested BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 were between 0.2 and 1.2. There is hence no substantially more active dimer compared to its respective monomer.

Example A16

Monomer to Dimer Conversion after Three Freeze/Thaw Cycles

(145) Bispecific BCMA/CD3 antibody monomer were subjected to three freeze/thaw cycles followed by high performance SEC to determine the percentage of initially monomeric antibody, which had been converted into antibody dimer.

(146) 15 g of monomeric antibody were adjusted to a concentration of 250 g/ml with generic buffer and then frozen at 80 C. for 30 min followed by thawing for 30 min at room temperature. After three freeze/thaw cycles the dimer content was determined by HP-SEC. To this end, 15 g aliquots of the monomeric isoforms of the antibodies were thawed and equalized to a concentration of 250 g/ml in the original SEC buffer (10 mM citric acid75 mM lysine HCl4% trehalosepH 7.2) followed by incubation at 37 C. for 7 days. A high resolution SEC Column TSK Gel G3000 SVVXL (Tosoh, Tokyo-Japan) was connected to an kta Purifier 10 FPLC (GE Lifesciences) equipped with an A905 Autosampler. Column equilibration and running buffer consisted of 100 mM KH2PO4200 mM Na2SO4 adjusted to pH 6.6. After 7 days of incubation, the antibody solution (15 g protein) was applied to the equilibrated column and elution was carried out at a flow rate of 0.75 ml/min at a maximum pressure of 7 MPa. The whole run was monitored at 280, 254 and 210 nm optical absorbance. Analysis was done by peak integration of the 210 nm signal recorded in the kta Unicorn software run evaluation sheet. Dimer content was calculated by dividing the area of the dimer peak by the total area of monomer plus dimer peak.

(147) The BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 presented with dimer percentages of 0.8 to 1.5% after three freeze/thaw cycles, which is considered good. However, the dimer conversion rates of BCMA/CD3 bispecific antibodies of the epitope cluster E1/E4 reached unfavorably high values, exceeding the threshold to disadvantageous dimer values of 2.5% (4.7% and 3.8%, respectively), see Table 11.

(148) TABLE-US-00011 TABLE 11 Percentage of monomeric versus dimeric BCMA/CD3 bispecific antibodies of epitope clusters E1/E4 (rows 1 and 2) and E3/E4 E7 (rows 3 and 4) after three freeze/thaw cycles as determined by High Performance Size Exclusion Chromatography (HP-SEC). BCMA/CD3 bispecific antibody Monomer [%] Dimer [%] 1 BCMA-54 95.3 4.7 2 BCMA-53 96.2 3.8 3 BCMA-30 98.5 1.5 4 BCMA-50 99.2 0.8

Example A17

Thermostability

(149) Temperature melting curves were determined by Differential Scanning calorimetry (DSC) to determine intrinsic biophysical protein stabilities of the BCMA/CD3 bispecific antibodies. These experiments were performed using a MicroCal LLC (Northampton, Mass., U.S.A) VP-DSC device. The energy uptake of a sample containing BCMA/CD3 bispecific antibody was recorded from 20 to 90 C. compared to a sample which just contained the antibody's formulation buffer.

(150) In detail, BCMA/CD3 bispecific antibodies were adjusted to a final concentration of 250 g/ml in storage buffer. 300 l of the prepared protein solutions were transferred into a deep well plate and placed into the cooled autosampler rack position of the DSC device. Additional wells were filled with the SEC running buffer as reference material for the measurement. For the measurement process the protein solution was transferred by the autosampler into a capillary. An additional capillary was filled with the SEC running buffer as reference. Heating and recording of required heating energy to heat up both capillaries at equal temperature ranging from 20 to 90 C. was done for all samples.

(151) For recording of the respective melting curve, the overall sample temperature was increased stepwise. At each temperature T energy uptake of the sample and the formulation buffer reference was recorded. The difference in energy uptake Cp (kcal/mole/ C.) of the sample minus the reference was plotted against the respective temperature. The melting temperature is defined as the temperature at the first maximum of energy uptake.

(152) All tested BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 showed favorable thermostability with melting temperatures above 60 C., more precisely between 62 C. and 63 C.

Example A18

Exclusion of Plasma Interference by Flow Cytometry

(153) To determine potential interaction of BCMA/CD3 bispecific antibodies with human plasma proteins, a plasma interference test was established. To this end, 10 g/ml of the respective BCMA/CD3 bispecific antibodies were incubated for one hour at 37 C. in 90% human plasma. Subsequently, the binding to human BCMA expressing CHO cells was determined by flow cytometry.

(154) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified antibody at a concentration of 5 g/ml. The cells were washed twice in PBS/2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS/2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS/2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(155) The obtained data were compared with a control assay using PBS instead of human plasma. Relative binding was calculated as follows:
(signal PBS sample/signal w/o detection agent)/(signal plasma sample/signal w/o detection agent).

(156) In this experiment it became obvious that there was no significant reduction of target binding of the respective BCMA/CD3 bispecific antibodies of the epitope cluster E3/E4E7 mediated by plasma proteins. The relative plasma interference value was between 1.280.38 and 1.290.31 (with a value of 2 being considered as lower threshold for interference signals).

Example A19

Therapeutic Efficacy of BCMA/CD3 Bispecific Antibodies in Human Tumor Xenograft Models

(157) On day 1 of the study, 510.sup.6 cells of the human cancer cell line NCI-H929 were subcutaneously injected in the right dorsal flank of female NOD/SCID mice.

(158) On day 9, when the mean tumor volume had reached about 100 mm.sup.3, in vitro expanded human CD3.sup.+ T cells were transplanted into the mice by injection of about 210.sup.7 cells into the peritoneal cavity of the animals. Mice of vehicle control group 1 (n=5) did not receive effector cells and were used as an untransplanted control for comparison with vehicle control group 2 (n=10, receiving effector cells) to monitor the impact of T cells alone on tumor growth.

(159) The antibody treatment started on day 13, when the mean tumor volume had reached about 200 mm.sup.3. The mean tumor size of each treatment group on the day of treatment start was not statistically different from any other group (analysis of variance). Mice were treated with 0.5 mg/kg/day of the BCMA/CD3 bispecific antibody BCMA-50CD3 (group 3, n=8) by intravenous bolus injection for 17 days.

(160) Tumors were measured by caliper during the study and progress evaluated by intergroup comparison of tumor volumes (TV). The tumor growth inhibition T/C [%] was determined by calculating TV as T/C %=100(median TV of analyzed group)/(median TV of control group 2). The results are shown in Table 12 and FIG. 16.

(161) TABLE-US-00012 TABLE 12 Median tumor volume (TV) and tumor growth inhibition (T/C) at days 13 to 30. Dose group Data d13 d14 d15 d16 d18 d19 d21 d23 d26 d28 d30 1 Vehi. med.TV 238 288 395 425 543 632 863 1067 1116 1396 2023 control [mm.sup.3] w/o T/C [%] 120 123 127 118 104 114 122 113 87 85 110 T cells 2 med.TV 198 235 310 361 525 553 706 942 1290 1636 1839 Vehicle [mm.sup.3] control T/C [%] 100 100 100 100 100 100 100 100 100 100 100 3 med.TV 215 260 306 309 192 131 64.1 0.0 0.0 0.0 0.0 BCMA- [mm.sup.3] 50 T/C [%] 108 111 98.6 85.7 36.5 23.7 9.1 0.0 0.0 0.0 0.0

Example A20

Exclusion of Lysis of Target Negative Cells

(162) An in vitro lysis assay was carried out using the BCMA-positive human multiple myeloma cell line NCI-H929 and purified T cells at an effector to target cell ratio of 5:1 and with an incubation time of 24 hours. The BCMA/CD3 bispecific antibody of epitope cluster E3/E4E7 (BCMA-50) showed high potency and efficacy in the lysis of NCI-H929. However, no lysis was detected in the BCMA negative cell lines HL60 (AML/myeloblast morphology), MES-SA (uterus sarcoma, fibroblast morphology), and SNU-16 (stomach carcinoma, epithelial morphology) for up to 500 nM of the antibody.

Example A21

Induction of T Cell Activation of Different PBMC Subsets

(163) A FACS-based cytotoxicity assay (48 h; E:T=10:1) was carried out using human multiple myeloma cell lines NCI-H929, L-363 and OPM-2 as target cells and different subsets of human PBMC (CD4.sup.+/CD8.sup.+/CD25.sup.+/CD69.sup.+) as effector cells. The results (see Table 13) show that the degree of activation, as measured by the EC.sub.50 value, is essentially in the same range for the different analyzed PBMC subsets.

(164) TABLE-US-00013 TABLE 13 EC50 values [ng/ml] of the BCMA/CD3 bispecific antibody BCMA-50 of epitope cluster E3/E4 E7 as measured in a 48-hour FACS-based cytotoxicity assay with different subsets of human PBMC as effector cells and different human multiple myeloma cell lines as target cells. EC.sub.50 [ng/ml] Cell line PBMC BCMA-50 CD3 NCI-H929 CD4.sup.+/CD25.sup.+ 0.88 CD8.sup.+/CD25.sup.+ 0.38 CD4.sup.+/CD69.sup.+ 0.41 CD8.sup.+/CD69.sup.+ 0.15 OPM-2 CD4.sup.+/CD25.sup.+ 5.06 CD8.sup.+/CD25.sup.+ 1.51 CD4.sup.+/CD69.sup.+ 3.52 CD8.sup.+/CD69.sup.+ 0.68 L-363 CD4.sup.+/CD25.sup.+ 0.72 CD8.sup.+/CD25.sup.+ 0.38 CD4.sup.+/CD69.sup.+ 0.53 CD8.sup.+/CD69.sup.+ 0.12

Example A22

Induction of Cytokine Release

(165) A FACS-based cytotoxicity assay (48 h; E:T=10:1) was carried out using human multiple myeloma cell lines NCI-H929, L-363 and OPM-2 as target cells and human PBMC as effector cells. The levels of cytokine release [pg/ml] were determined at increasing concentrations of a BCMA/CD3 bispecific antibody of epitope cluster E3/E4E7. The following cytokines were analyzed: Il-2, IL-6, IL-10, TNF and IFN-gamma. The results are shown in Table 14 and FIG. 17.

(166) TABLE-US-00014 TABLE 14 Release of IL-2, IL-6, IL-10, TNF and IFN-gamma [pg/ml] induced by 2.5 g/ml of a BCMA/CD3 bispecific antibody of epitope cluster E3/E4 E7 (BCMA-50) in a 48-hour FACS-based cytotoxicity assay with human PBMC as effector cells and different human multiple myeloma cell lines as target cells (E:T = 10:1). Cytokine levels [pg/ml] Cell line IL-2 IL-6 IL-10 TNF IFN-gamma NCI-H929 1865 664 3439 9878 79372 OPM-2 23 99 942 6276 23568 L-363 336 406 3328 4867 69687

Examples B

Example B1

Generation of CHO Cells Expressing Chimeric BCMA

(167) For the construction of the chimeric epitope mapping molecules, the amino acid sequence of the respective epitope domains or the single amino acid residue of human BCMA was changed to the murine sequence. The following molecules were constructed: Human BCMA ECD/E1 murine (SEQ ID NO: 1009)

(168) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 1 (amino acid residues 1-7 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 1-4 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 1-3 and G6Q mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E2 murine (SEQ ID NO: 1010)

(169) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 2 (amino acid residues 8-21 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 5-18 of SEQ ID NO: 1004 or 1008) S9F, Q10H, and N11S mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E3 murine (SEQ ID NO: 1011)

(170) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 3 (amino acid residues 24-41 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 21-36 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 31 and 32 and Q25H, S30N, L35A, and R39P mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E4 murine (SEQ ID NO: 1012)

(171) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 4 (amino acid residues 42-54 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 37-49 of SEQ ID NO: 1004 or 1008) N42D, A43P, N47S, N53Y and A54T mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E5 murine (SEQ ID NO: 1013)

(172) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 22 of SEQ ID NO: 1002 or 1007 (isoleucine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (lysine, position 19) I22K mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E6 murine (SEQ ID NO: 1014)

(173) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 25 of SEQ ID NO: 1002 or 1007 (glutamine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (histidine, position 22) Q25H mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E7 murine (SEQ ID NO: 1015)

(174) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 39 of SEQ ID NO: 1002 or 1007 (arginine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (proline, position 34) R39P mutation in SEQ ID NO: 1002 or 1007

(175) The cDNA constructs were cloned into the mammalian expression vector pEF-DHFR and stably transfected into CHO cells. The expression of human BCMA on CHO cells was verified in a FACS assay using a monoclonal anti-human BCMA antibody. Murine BCMA expression was demonstrated with a monoclonal anti-mouse BCMA-antibody. The used concentration of the BCMA antibodies was 10 g/ml in PBS/2% FCS. Bound monoclonal antibodies were detected with an anti-rat-IgG-Fcy-PE (1:100 in PBS/2% FCS; Jackson-Immuno-Research #112-116-071). As negative control, cells were incubated with PBS/2% FCS instead of the first antibody. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6). The surface expression of human-murine BCMA chimeras, transfected CHO cells were analyzed and confirmed in a flow cytometry assay with different anti-BCMA antibodies (FIG. 2).

Example B2

2.1 Transient Expression in HEK 293 Cells

(176) Clones of the expression plasmids with sequence-verified nucleotide sequences were used for transfection and protein expression in the FreeStyle 293 Expression System (Invitrogen GmbH, Karlsruhe, Germany) according to the manufacturer's protocol. Supernatants containing the expressed proteins were obtained, cells were removed by centrifugation and the supernatants were stored at 20 C.

2.2 Stable Expression in CHO Cells

(177) Clones of the expression plasmids with sequence-verified nucleotide sequences were transfected into DHFR deficient CHO cells for eukaryotic expression of the constructs. Eukaryotic protein expression in DHFR deficient CHO cells was performed as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566. Gene amplification of the constructs was induced by increasing concentrations of methotrexate (MTX) to a final concentration of 20 nM MTX. After two passages of stationary culture the cells were grown in roller bottles with nucleoside-free HyQ PF CHO liquid soy medium (with 4.0 mM L-Glutamine with 0.1% Pluronic F-68; HyClone) for 7 days before harvest. The cells were removed by centrifugation and the supernatant containing the expressed protein was stored at 20 C.

Example B3

Epitope Clustering of Murine scFv-Fragments

(178) Cells transfected with human or murine BCMA, or with chimeric BCMA molecules were stained with crude, undiluted periplasmic extract containing scFv binding to human/macaque BCMA. Bound scFv were detected with 1 g/ml of an anti-FLAG antibody (Sigma F1804) and a R-PE-labeled anti-mouse Fc gamma-specific antibody (1:100; Dianova #115-116-071). All antibodies were diluted in PBS with 2% FCS. As negative control, cells were incubated with PBS/2% FCS instead of the periplasmic extract. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6).

Example B4

Procurement of Different Recombinant Forms of Soluble Human and Macaque BCMA

(179) The coding sequences of human and rhesus BCMA (as published in GenBank, accession numbers NM_001192 [human], XM_001106892 [rhesus]) coding sequences of human albumin, human Fc1 and murine albumin were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of human and macaque BCMA respectively and human albumin, human IgG1 Fc and murine albumin respectively as well as soluble proteins comprising only the extracellular domains of BCMA. To generate the constructs for expression of the soluble human and macaque BCMA proteins, cDNA fragments were obtained by PCR mutagenesis of the full-length BCMA cDNAs described above and molecular cloning according to standard protocols.

(180) For the fusions with human albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and rhesus BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of human serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(181) For the fusions with murine IgG1, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of the hinge and Fc gamma portion of human IgG1, followed in frame by the coding sequence of a hexahistidine tag and a stop codon.

(182) For the fusions with murine albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of murine serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(183) For the soluble extracellular domain constructs, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly1-linker, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(184) The cDNA fragments were also designed to introduce restriction sites at the beginning and at the end of the fragments. The introduced restriction sites, EcoRI at the 5 end and SalI at the 3 end, were utilized in the following cloning procedures. The cDNA fragments were cloned via EcoRI and SalI into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). The aforementioned procedures were all carried out according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y. (2001)).

Example B5

Biacore-Based Determination of Bispecific Antibody Affinity to Human and Macaque BCMA and CD3

(185) Biacore analysis experiments were performed using recombinant BCMA fusion proteins with human serum albumin (ALB) to determine BCMA target binding. For CD3 affinity measurements, recombinant fusion proteins having the N-terminal 27 amino acids of the CD3 epsilon (CD3e) fused to human antibody Fc portion were used. This recombinant protein exists in a human CD3e1-27 version and in a cynomolgous CD3e version, both bearing the epitope of the CD3 binder in the bispecific antibodies.

(186) In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 100 to 150 RU of the respective recombinant antigen using acetate buffer pH4.5 according to the manufacturer's manual. The bispecific antibody samples were loaded in five concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP running buffer (GE Healthcare). Flow rate was 30 to 35 l/min for 3 min, then HBS-EP running buffer was applied for 8 min again at a flow rate of 30 to 35 l/ml. Regeneration of the chip was performed using 10 mM glycine 0.5 M NaCl pH 2.45. Data sets were analyzed using BiaEval Software. In general two independent experiments were performed.

Example B6

Flow Cytometry Analysis

(187) Functionality and binding strength of affinity matured scFv molecules were analyzed in FACS using human and macaque BCMA transfected CHO cells. In brief, approximately 10.sup.5 cells were incubated with 50 l of serial 1:3 dilutions of periplasmatic E. coli cell extracts for 50 min on ice. After washing with PBS/10% FCS/0.05% sodium azide, the cells were incubated with 30 l of Flag-M2 IgG (Sigma, 1:900 in PBS/10% FCS/0.05% sodium azide) for 40 min on ice. After a second wash, the cells were incubated with 30 l of a R-Phycoerythrin (PE)-labeled goat anti-mouse IgG (Jackson ImmunoResearch, 1:100 in PBS/10% FCS/0.05% sodium azide) for 40 min on ice. The cells were then washed again and resuspended in 200 l PBS/10% FCS/0.05% sodium azide. The relative fluorescence of stained cells was measured using a FACSCanto flow cytometer (BD). The results are depicted as FACS histograms, plotting the log of fluorescence intensity versus relative cell number (see FIG. B4).

Example B7

Bispecific Binding and Interspecies Cross-Reactivity

(188) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS.

Example B8

Scatchard-Based Determination of Bispecific-Antibody Affinity to Human and Macaque BCMA

(189) For Scatchard analysis, saturation binding experiments are performed using a monovalent detection system developed at Micromet (anti-His Fab/Alexa 488) to precisely determine monovalent binding of the bispecific antibodies to the respective cell line.

(190) 210.sup.4 cells of the respective cell line (recombinantly human BCMA-expressing CHO cell line, recombinantly macaque BCMA-expressing CHO cell line) are incubated with each 50 l of a triplet dilution series (eight dilutions at 1:2) of the respective BCMA bispecific antibody starting at 100 nM followed by 16 h incubation at 4 C. under agitation and one residual washing step. Then, the cells are incubated for further 30 min with 30 l of an anti-His Fab/Alexa488 solution (Micromet; 30 g/ml). After one washing step, the cells are resuspended in 150 l FACS buffer containing 3.5% formaldehyde, incubated for further 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS Cantoll machine and FACS Diva software. Data are generated from two independent sets of experiments. Values are plotted as hyperbole binding curves. Respective Scatchard analysis is calculated to extrapolate maximal binding (Bmax). The concentrations of bispecific antibodies at half-maximal binding are determined reflecting the respective KDs. Values of triplicate measurements are plotted as hyperbolic curves. Maximal binding is determined using Scatchard evaluation and the respective KDs are calculated.

Example B9

Cytotoxic Activity

9.1 Chromium Release Assay with Stimulated Human T Cells

(191) Stimulated T cells enriched for CD8.sup.+ T cells were obtained as described below.

(192) A petri dish (145 mm diameter, Greiner bio-one GmbH, Kremsmunster) was coated with a commercially available anti-CD3 specific antibody (OKT3, Orthoclone) in a final concentration of 1 g/ml for 1 hour at 37 C. Unbound protein was removed by one washing step with PBS. 3-510.sup.7 human PBMC were added to the precoated petri dish in 120 ml of RPMI 1640 with stabilized glutamine/10% FCS/IL-2 20 U/ml (Proleukin, Chiron) and stimulated for 2 days. On the third day, the cells were collected and washed once with RPMI 1640. IL-2 was added to a final concentration of 20 U/ml and the cells were cultured again for one day in the same cell culture medium as above.

(193) CD8.sup.+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4.sup.+ T cells and CD56.sup.+ NK cells using Dynal-Beads according to the manufacturer's protocol.

(194) Macaque or human BCMA-transfected CHO target cells were washed twice with PBS and labeled with 11.1 MBq .sup.51Cr in a final volume of 100 l RPMI with 50% FCS for 60 minutes at 37 C. Subsequently, the labeled target cells were washed 3 times with 5 ml RPMI and then used in the cytotoxicity assay. The assay was performed in a 96-well plate in a total volume of 200 l supplemented RPMI with an E:T ratio of 10:1. A starting concentration of 0.01-1 g/ml of purified bispecific antibody and threefold dilutions thereof were used. Incubation time for the assay was 18 hours. Cytotoxicity was determined as relative values of released chromium in the supernatant relative to the difference of maximum lysis (addition of Triton-X) and spontaneous lysis (without effector cells). All measurements were carried out in quadruplicates. Measurement of chromium activity in the supernatants was performed in a Wizard 3 gamma counter (Perkin Elmer Life Sciences GmbH, Kln, Germany). Analysis of the results was carried out with Prism 5 for Windows (version 5.0, GraphPad Software Inc., San Diego, Calif., USA). EC50 values calculated by the analysis program from the sigmoidal dose response curves were used for comparison of cytotoxic activity.

9.2 FACS-Based Cytotoxicity Assay with Unstimulated Human PBMC

(195) Isolation of Effector Cells

(196) Human peripheral blood mononuclear cells (PBMC) were prepared by Ficoll density gradient centrifugation from enriched lymphocyte preparations (buffy coats), a side product of blood banks collecting blood for transfusions. Buffy coats were supplied by a local blood bank and PBMC were prepared on the same day of blood collection. After Ficoll density centrifugation and extensive washes with Dulbecco's PBS (Gibco), remaining erythrocytes were removed from PBMC via incubation with erythrocyte lysis buffer (155 mM NH.sub.4Cl, 10 mM KHCO.sub.3, 100 M EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100g. Remaining lymphocytes mainly encompass B and T lymphocytes, NK cells and monocytes. PBMC were kept in culture at 37 C./5% CO.sub.2 in RPMI medium (Gibco) with 10% FCS (Gibco).

(197) Depletion of CD14.sup.+ and CD56.sup.+ Cells

(198) For depletion of CD14.sup.+ cells, human CD14 MicroBeads (Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted and centrifuged for 10 min at room temperature with 300g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 L/10.sup.7 cells; PBS (Invitrogen, #20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA (Sigma-Aldrich, #E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20 L/10.sup.7 cells) were added and incubated for 15 min at 4-8 C. The cells were washed with MACS isolation buffer (1-2 mL/10.sup.7 cells). After centrifugation (see above), supernatant was discarded and cells resuspended in MACS isolation buffer (500 L/10.sup.8 cells). CD14/CD56 negative cells were then isolated using LS Columns (Miltenyi Biotec, #130-042-401). PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium i.e. RPMI1640 (Biochrom AG, #FG1215) supplemented with 10% FBS (Biochrom AG, #S0115), 1 non-essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, #L1613), 1 mM sodium pyruvate (Biochrom AG, #L0473) and 100 U/mL penicillin/streptomycin (Biochrom AG, #A2213) at 37 C. in an incubator until needed.

(199) Target Cell Labeling

(200) For the analysis of cell lysis in flow cytometry assays, the fluorescent membrane dye DiOC.sub.13 (DiO) (Molecular Probes, #V22886) was used to label human BCMA- or macaque BCMA-transfected CHO cells as target cells and distinguish them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10.sup.6 cell/mL in PBS containing 2% (v/v) FBS and the membrane dye DiO (5 L/10.sup.6 cells). After incubation for 3 min at 37 C., cells were washed twice in complete RPMI medium and the cell number adjusted to 1.2510.sup.5 cells/mL. The vitality of cells was determined using 0.5% (v/v) isotonic EosinG solution (Roth, #45380).

(201) Flow Cytometry Based Analysis

(202) This assay was designed to quantify the lysis of macaque or human BCMA-transfected CHO cells in the presence of serial dilutions of BCMA bispecific antibodies.

(203) Equal volumes of DiO-labeled target cells and effector cells (i.e., PBMC w/o CD14.sup.+ cells) were mixed, resulting in an E:T cell ratio of 10:1. 160 L of this suspension were transferred to each well of a 96-well plate. 40 L of serial dilutions of the BCMA bispecific antibodies and a negative control bispecific (an CD3-based bispecific antibody recognizing an irrelevant target antigen) or RPMI complete medium as an additional negative control were added. The bispecific antibody-mediated cytotoxic reaction proceeded for 48 hours in a 7% CO.sub.2 humidified incubator. Then cells were transferred to a new 96-well plate and loss of target cell membrane integrity was monitored by adding propidium iodide (PI) at a final concentration of 1 g/mL. PI is a membrane impermeable dye that normally is excluded from viable cells, whereas dead cells take it up and become identifiable by fluorescent emission.

(204) Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(205) Target cells were identified as DiO-positive cells. PI-negative target cells were classified as living target cells. Percentage of cytotoxicity was calculated according to the following formula:

(206) $\mathrm{Cytotoxicity}\left[\%\right]=\frac{n_{\mathrm{dead}\mathrm{target}\mathrm{cells}}}{n_{\mathrm{target}\mathrm{cells}}}100$$n=\mathrm{number}\mathrm{of}\mathrm{events}$

(207) Using GraphPad Prism 5 software (Graph Pad Software, San Diego), the percentage of cytotoxicity was plotted against the corresponding bispecific antibody concentrations. Dose response curves were analyzed with the four parametric logistic regression models for evaluation of sigmoid dose response curves with fixed hill slope and EC50 values were calculated.

Example B10

Exclusion of Cross-Reactivity with BAFF-Receptor

(208) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson). The bispecific binders were shown to not be cross-reactive with BAFF receptor.

Example B11

Cytotoxic Activity

(209) The potency of human-like BCMA bispecific antibodies in redirecting effector T cells against BCMA-expressing target cells is analyzed in five additional in vitro cytotoxicity assays:

(210) 1. The potency of BCMA bispecific antibodies in redirecting stimulated human effector T cells against a BCMA-positive (human) tumor cell line is measured in a 51-chromium release assay.

(211) 2. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against human BCMA-transfected CHO cells is measured in a FACS-based cytotoxicity assay.

(212) 3. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against a BCMA-positive (human) tumor cell line is measured in a FACS-based cytotoxicity assay.

(213) 4. For confirmation that the cross-reactive BCMA bispecific antibodies are capable of redirecting macaque T cells against macaque BCMA-transfected CHO cells, a FACS-based cytotoxicity assay is performed with a macaque T cell line as effector T cells.

(214) 5. The potency gap between monomeric and dimeric forms of BCMA bispecific antibodies is determined in a 51-chromium release assay using human BCMA-transfected CHO cells as target cells and stimulated human T cells as effector cells.

Examples C

Example C1

Generation of CHO Cells Expressing Chimeric BCMA

(215) For the construction of the chimeric epitope mapping molecules, the amino acid sequence of the respective epitope domains or the single amino acid residue of human BCMA was changed to the murine sequence. The following molecules were constructed: Human BCMA ECD/E1 murine (SEQ ID NO: 1009)

(216) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 1 (amino acid residues 1-7 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 1-4 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 1-3 and G6Q mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E2 murine (SEQ ID NO: 1010)

(217) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 2 (amino acid residues 8-21 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 5-18 of SEQ ID NO: 1004 or 1008) S9F, Q10H, and N11S mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E3 murine (SEQ ID NO: 1011)

(218) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 3 (amino acid residues 24-41 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 21-36 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 31 and 32 and Q25H, S30N, L35A, and R39P mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E4 murine (SEQ ID NO: 1012)

(219) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 4 (amino acid residues 42-54 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 37-49 of SEQ ID NO: 1004 or 1008) N42D, A43P, N47S, N53Y and A54T mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E5 murine (SEQ ID NO: 1013)

(220) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 22 of SEQ ID NO: 1002 or 1007 (isoleucine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (lysine, position 19) I22K mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E6 murine (SEQ ID NO: 1014)

(221) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 25 of SEQ ID NO: 1002 or 1007 (glutamine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (histidine, position 22) Q25H mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E7 murine (SEQ ID NO: 1015)

(222) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 39 of SEQ ID NO: 1002 or 1007 (arginine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (proline, position 34) R39P mutation in SEQ ID NO: 1002 or 1007

(223) The cDNA constructs were cloned into the mammalian expression vector pEF-DHFR and stably transfected into CHO cells. The expression of human BCMA on CHO cells was verified in a FACS assay using a monoclonal anti-human BCMA antibody. Murine BCMA expression was demonstrated with a monoclonal anti-mouse BCMA-antibody. The used concentration of the BCMA antibodies was 10 g/ml in PBS/2% FCS. Bound monoclonal antibodies were detected with an anti-rat-IgG-Fcy-PE (1:100 in PBS/2% FCS; Jackson-Immuno-Research #112-116-071). As negative control, cells were incubated with PBS/2% FCS instead of the first antibody. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6). The surface expression of human-murine BCMA chimeras, transfected CHO cells were analyzed and confirmed in a flow cytometry assay with different anti-BCMA antibodies (FIG. 2).

Example C2

2.1 Transient Expression in HEK 293 Cells

(224) Clones of the expression plasmids with sequence-verified nucleotide sequences were used for transfection and protein expression in the FreeStyle 293 Expression System (Invitrogen GmbH, Karlsruhe, Germany) according to the manufacturer's protocol. Supernatants containing the expressed proteins were obtained, cells were removed by centrifugation and the supernatants were stored at 20 C.

2.2 Stable Expression in CHO Cells

(225) Clones of the expression plasmids with sequence-verified nucleotide sequences were transfected into DHFR deficient CHO cells for eukaryotic expression of the constructs. Eukaryotic protein expression in DHFR deficient CHO cells was performed as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566. Gene amplification of the constructs was induced by increasing concentrations of methotrexate (MTX) to a final concentration of 20 nM MTX. After two passages of stationary culture the cells were grown in roller bottles with nucleoside-free HyQ PF CHO liquid soy medium (with 4.0 mM L-Glutamine with 0.1% Pluronic F-68; HyClone) for 7 days before harvest. The cells were removed by centrifugation and the supernatant containing the expressed protein was stored at 20 C.

Example C3

Epitope Clustering of Murine scFv-Fragments

(226) Cells transfected with human or murine BCMA, or with chimeric BCMA molecules were stained with crude, undiluted periplasmic extract containing scFv binding to human/macaque BCMA. Bound scFv were detected with 1 g/ml of an anti-FLAG antibody (Sigma F1804) and a R-PE-labeled anti-mouse Fc gamma-specific antibody (1:100; Dianova #115-116-071). All antibodies were diluted in PBS with 2% FCS. As negative control, cells were incubated with PBS/2% FCS instead of the periplasmic extract. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6).

Example C4

Procurement of Different Recombinant Forms of Soluble Human and Macaque BCMA

(227) The coding sequences of human and rhesus BCMA (as published in GenBank, accession numbers NM_001192 [human], XM_001106892 [rhesus]) coding sequences of human albumin, human Fc1 and murine albumin were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of human and macaque BCMA respectively and human albumin, human IgG1 Fc and murine albumin respectively as well as soluble proteins comprising only the extracellular domains of BCMA. To generate the constructs for expression of the soluble human and macaque BCMA proteins, cDNA fragments were obtained by PCR mutagenesis of the full-length BCMA cDNAs described above and molecular cloning according to standard protocols.

(228) For the fusions with human albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and rhesus BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of human serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(229) For the fusions with murine IgG1, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of the hinge and Fc gamma portion of human IgG1, followed in frame by the coding sequence of a hexahistidine tag and a stop codon.

(230) For the fusions with murine albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of murine serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(231) For the soluble extracellular domain constructs, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly1-linker, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(232) The cDNA fragments were also designed to introduce restriction sites at the beginning and at the end of the fragments. The introduced restriction sites, EcoRI at the 5 end and SalI at the 3 end, were utilized in the following cloning procedures. The cDNA fragments were cloned via EcoRI and SalI into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). The aforementioned procedures were all carried out according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y. (2001)).

Example C5

Biacore-Based Determination of Bispecific Antibody Affinity to Human and Macaque BCMA and CD3

(233) Biacore analysis experiments are performed using recombinant BCMA fusion proteins with human serum albumin (ALB) to determine BCMA target binding. For CD3 affinity measurements, recombinant fusion proteins having the N-terminal 27 amino acids of the CD3 epsilon (CD3e) fused to human antibody Fc portion are used. This recombinant protein exists in a human CD3e1-27 version and in a cynomolgous CD3e version, both bearing the epitope of the CD3 binder in the bispecific antibodies.

(234) In detail, CM5 Sensor Chips (GE Healthcare) are immobilized with approximately 100 to 150 RU of the respective recombinant antigen using acetate buffer pH4.5 according to the manufacturer's manual. The bispecific antibody samples are loaded in five concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP running buffer (GE Healthcare). Flow rate is 30 to 35 l/min for 3 min, then HBS-EP running buffer is applied for 8 min again at a flow rate of 30 to 35 l/ml. Regeneration of the chip is performed using 10 mM glycine 0.5 M NaCl pH 2.45. Data sets are analyzed using BiaEval Software. In general two independent experiments were performed.

Example C6

Flow Cytometry Analysis

(235) Functionality and binding strength of affinity matured scFv molecules were analyzed in FACS using human and macaque BCMA transfected CHO cells. In brief, approximately 10.sup.5 cells were incubated with 50 l of serial 1:3 dilutions of periplasmatic E. coli cell extracts for 50 min on ice. After washing with PBS/10% FCS/0.05% sodium azide, the cells were incubated with 30 l of Flag-M2 IgG (Sigma, 1:900 in PBS/10% FCS/0.05% sodium azide) for 40 min on ice. After a second wash, the cells were incubated with 30 l of a R-Phycoerythrin (PE)-labeled goat anti-mouse IgG (Jackson ImmunoResearch, 1:100 in PBS/10% FCS/0.05% sodium azide) for 40 min on ice. The cells were then washed again and resuspended in 200 l PBS/10% FCS/0.05% sodium azide. The relative fluorescence of stained cells was measured using a FACSCanto flow cytometer (BD). The results are depicted as FACS histograms, plotting the log of fluorescence intensity versus relative cell number (see FIG. C4).

Example C7

Bispecific Binding and Interspecies Cross-Reactivity

(236) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS.

Example C8

Scatchard-Based Determination of Bispecific-Antibody Affinity to Human and Macaque BCMA

(237) For Scatchard analysis, saturation binding experiments are performed using a monovalent detection system developed at Micromet (anti-His Fab/Alexa 488) to precisely determine monovalent binding of the bispecific antibodies to the respective cell line.

(238) 210.sup.4 cells of the respective cell line (recombinantly human BCMA-expressing CHO cell line, recombinantly macaque BCMA-expressing CHO cell line) are incubated with each 50 l of a triplet dilution series (eight dilutions at 1:2) of the respective BCMA bispecific antibody starting at 100 nM followed by 16 h incubation at 4 C. under agitation and one residual washing step. Then, the cells are incubated for further 30 min with 30 l of an anti-His Fab/Alexa488 solution (Micromet; 30 g/ml). After one washing step, the cells are resuspended in 150 l FACS buffer containing 3.5% formaldehyde, incubated for further 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS Cantoll machine and FACS Diva software. Data are generated from two independent sets of experiments. Values are plotted as hyperbole binding curves. Respective Scatchard analysis is calculated to extrapolate maximal binding (Bmax). The concentrations of bispecific antibodies at half-maximal binding are determined reflecting the respective KDs. Values of triplicate measurements are plotted as hyperbolic curves. Maximal binding is determined using Scatchard evaluation and the respective KDs are calculated.

Example C9

Cytotoxic Activity

9.1 Chromium Release Assay with Stimulated Human T Cells

(239) Stimulated T cells enriched for CD8.sup.+ T cells were obtained as described below.

(240) A petri dish (145 mm diameter, Greiner bio-one GmbH, Kremsmunster) was coated with a commercially available anti-CD3 specific antibody (OKT3, Orthoclone) in a final concentration of 1 g/ml for 1 hour at 37 C. Unbound protein was removed by one washing step with PBS. 3-510.sup.7 human PBMC were added to the precoated petri dish in 120 ml of RPMI 1640 with stabilized glutamine/10% FCS/IL-2 20 U/ml (Proleukin, Chiron) and stimulated for 2 days. On the third day, the cells were collected and washed once with RPMI 1640. IL-2 was added to a final concentration of 20 U/ml and the cells were cultured again for one day in the same cell culture medium as above.

(241) CD8.sup.+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4.sup.+ T cells and CD56.sup.+ NK cells using Dynal-Beads according to the manufacturer's protocol.

(242) Macaque or human BCMA-transfected CHO target cells were washed twice with PBS and labeled with 11.1 MBq .sup.51Cr in a final volume of 100 l RPMI with 50% FCS for 60 minutes at 37 C. Subsequently, the labeled target cells were washed 3 times with 5 ml RPMI and then used in the cytotoxicity assay. The assay was performed in a 96-well plate in a total volume of 200 l supplemented RPMI with an E:T ratio of 10:1. A starting concentration of 0.01-1 g/ml of purified bispecific antibody and threefold dilutions thereof were used. Incubation time for the assay was 18 hours. Cytotoxicity was determined as relative values of released chromium in the supernatant relative to the difference of maximum lysis (addition of Triton-X) and spontaneous lysis (without effector cells). All measurements were carried out in quadruplicates. Measurement of chromium activity in the supernatants was performed in a Wizard 3 gamma counter (Perkin Elmer Life Sciences GmbH, Kln, Germany). Analysis of the results was carried out with Prism 5 for Windows (version 5.0, GraphPad Software Inc., San Diego, Calif., USA). EC50 values calculated by the analysis program from the sigmoidal dose response curves were used for comparison of cytotoxic activity.

9.2 FACS-Based Cytotoxicity Assay with Unstimulated Human PBMC

(243) Isolation of Effector Cells

(244) Human peripheral blood mononuclear cells (PBMC) were prepared by Ficoll density gradient centrifugation from enriched lymphocyte preparations (buffy coats), a side product of blood banks collecting blood for transfusions. Buffy coats were supplied by a local blood bank and PBMC were prepared on the same day of blood collection. After Ficoll density centrifugation and extensive washes with Dulbecco's PBS (Gibco), remaining erythrocytes were removed from PBMC via incubation with erythrocyte lysis buffer (155 mM NH.sub.4Cl, 10 mM KHCO.sub.3, 100 M EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100g. Remaining lymphocytes mainly encompass B and T lymphocytes, NK cells and monocytes. PBMC were kept in culture at 37 C./5% CO.sub.2 in RPMI medium (Gibco) with 10% FCS (Gibco).

(245) Depletion of CD14.sup.+ and CD56.sup.+ Cells

(246) For depletion of CD14.sup.+ cells, human CD14 MicroBeads (Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted and centrifuged for 10 min at room temperature with 300g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 L/10.sup.7 cells; PBS (Invitrogen, #20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA (Sigma-Aldrich, #E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20 L/10.sup.7 cells) were added and incubated for 15 min at 4-8 C. The cells were washed with MACS isolation buffer (1-2 mL/10.sup.7 cells). After centrifugation (see above), supernatant was discarded and cells resuspended in MACS isolation buffer (500 L/10.sup.8 cells). CD14/CD56 negative cells were then isolated using LS Columns (Miltenyi Biotec, #130-042-401). PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium i.e. RPMI1640 (Biochrom AG, #FG1215) supplemented with 10% FBS (Biochrom AG, #S0115), 1 non-essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, #L1613), 1 mM sodium pyruvate (Biochrom AG, #L0473) and 100 U/mL penicillin/streptomycin (Biochrom AG, #A2213) at 37 C. in an incubator until needed.

(247) Target Cell Labeling

(248) For the analysis of cell lysis in flow cytometry assays, the fluorescent membrane dye DiOC.sub.13 (DiO) (Molecular Probes, #V22886) was used to label human BCMA- or macaque BCMA-transfected CHO cells as target cells and distinguish them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10.sup.6 cell/mL in PBS containing 2% (v/v) FBS and the membrane dye DiO (5 L/10.sup.6 cells). After incubation for 3 min at 37 C., cells were washed twice in complete RPMI medium and the cell number adjusted to 1.2510.sup.5 cells/mL. The vitality of cells was determined using 0.5% (v/v) isotonic EosinG solution (Roth, #45380).

(249) Flow Cytometry Based Analysis

(250) This assay was designed to quantify the lysis of macaque or human BCMA-transfected CHO cells in the presence of serial dilutions of BCMA bispecific antibodies.

(251) Equal volumes of DiO-labeled target cells and effector cells (i.e., PBMC w/o CD14.sup.+ cells) were mixed, resulting in an E:T cell ratio of 10:1. 160 L of this suspension were transferred to each well of a 96-well plate. 40 L of serial dilutions of the BCMA bispecific antibodies and a negative control bispecific (an CD3-based bispecific antibody recognizing an irrelevant target antigen) or RPMI complete medium as an additional negative control were added. The bispecific antibody-mediated cytotoxic reaction proceeded for 48 hours in a 7% CO.sub.2 humidified incubator. Then cells were transferred to a new 96-well plate and loss of target cell membrane integrity was monitored by adding propidium iodide (PI) at a final concentration of 1 g/mL. PI is a membrane impermeable dye that normally is excluded from viable cells, whereas dead cells take it up and become identifiable by fluorescent emission.

(252) Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(253) Target cells were identified as DiO-positive cells. PI-negative target cells were classified as living target cells. Percentage of cytotoxicity was calculated according to the following formula:

(254) $\mathrm{Cytotoxicity}\left[\%\right]=\frac{n_{\mathrm{dead}\mathrm{target}\mathrm{cells}}}{n_{\mathrm{target}\mathrm{cells}}}100$$n=\mathrm{number}\mathrm{of}\mathrm{events}$

(255) Using GraphPad Prism 5 software (Graph Pad Software, San Diego), the percentage of cytotoxicity was plotted against the corresponding bispecific antibody concentrations. Dose response curves were analyzed with the four parametric logistic regression models for evaluation of sigmoid dose response curves with fixed hill slope and EC50 values were calculated.

Example C10

Exclusion of Cross-Reactivity with BAFF-Receptor

(256) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson). The bispecific binders were shown to not be cross-reactive with BAFF receptor.

Example C11

Cytotoxic Activity

(257) The potency of human-like BCMA bispecific antibodies in redirecting effector T cells against BCMA-expressing target cells is analyzed in five additional in vitro cytotoxicity assays:

(258) 1. The potency of BCMA bispecific antibodies in redirecting stimulated human effector T cells against a BCMA-positive (human) tumor cell line is measured in a 51-chromium release assay.

(259) 2. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against human BCMA-transfected CHO cells is measured in a FACS-based cytotoxicity assay.

(260) 3. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against a BCMA-positive (human) tumor cell line is measured in a FACS-based cytotoxicity assay.

(261) 4. For confirmation that the cross-reactive BCMA bispecific antibodies are capable of redirecting macaque T cells against macaque BCMA-transfected CHO cells, a FACS-based cytotoxicity assay is performed with a macaque T cell line as effector T cells.

(262) 5. The potency gap between monomeric and dimeric forms of BCMA bispecific antibodies is determined in a 51-chromium release assay using human BCMA-transfected CHO cells as target cells and stimulated human T cells as effector cells.

Examples D

Example D1

Generation of CHO Cells Expressing Chimeric BCMA

(263) For the construction of the chimeric epitope mapping molecules, the amino acid sequence of the respective epitope domains or the single amino acid residue of human BCMA was changed to the murine sequence. The following molecules were constructed: Human BCMA ECD/E1 murine (SEQ ID NO: 1009)

(264) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 1 (amino acid residues 1-7 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 1-4 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 1-3 and G6Q mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E2 murine (SEQ ID NO: 1010)

(265) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 2 (amino acid residues 8-21 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 5-18 of SEQ ID NO: 1004 or 1008) S9F, Q10H, and N11S mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E3 murine (SEQ ID NO: 1011)

(266) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 3 (amino acid residues 24-41 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 21-36 of SEQ ID NO: 1004 or 1008) deletion of amino acid residues 31 and 32 and Q25H, S30N, L35A, and R39P mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E4 murine (SEQ ID NO: 1012)

(267) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein epitope cluster 4 (amino acid residues 42-54 of SEQ ID NO: 1002 or 1007) is replaced by the respective murine cluster (amino acid residues 37-49 of SEQ ID NO: 1004 or 1008) N42D, A43P, N47S, N53Y and A54T mutations in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E5 murine (SEQ ID NO: 1013)

(268) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 22 of SEQ ID NO: 1002 or 1007 (isoleucine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (lysine, position 19) I22K mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E6 murine (SEQ ID NO: 1014)

(269) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 25 of SEQ ID NO: 1002 or 1007 (glutamine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (histidine, position 22) Q25H mutation in SEQ ID NO: 1002 or 1007 Human BCMA ECD/E7 murine (SEQ ID NO: 1015)

(270) Chimeric extracellular BCMA domain: Human extracellular BCMA domain wherein the amino acid residue at position 39 of SEQ ID NO: 1002 or 1007 (arginine) is replaced by its respective murine amino acid residue of SEQ ID NO: 1004 or 1008 (proline, position 34) R39P mutation in SEQ ID NO: 1002 or 1007

(271) The cDNA constructs were cloned into the mammalian expression vector pEF-DHFR and stably transfected into CHO cells. The expression of human BCMA on CHO cells was verified in a FACS assay using a monoclonal anti-human BCMA antibody. Murine BCMA expression was demonstrated with a monoclonal anti-mouse BCMA-antibody. The used concentration of the BCMA antibodies was 10 g/ml in PBS/2% FCS. Bound monoclonal antibodies were detected with an anti-rat-IgG-Fcy-PE (1:100 in PBS/2% FCS; Jackson-Immuno-Research #112-116-071). As negative control, cells were incubated with PBS/2% FCS instead of the first antibody. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6). The surface expression of human-murine BCMA chimeras, transfected CHO cells were analyzed and confirmed in a flow cytometry assay with different anti-BCMA antibodies (FIG. 2).

Example D2

2.1 Transient Expression in HEK 293 Cells

(272) Clones of the expression plasmids with sequence-verified nucleotide sequences were used for transfection and protein expression in the FreeStyle 293 Expression System (Invitrogen GmbH, Karlsruhe, Germany) according to the manufacturer's protocol. Supernatants containing the expressed proteins were obtained, cells were removed by centrifugation and the supernatants were stored at 20 C.

2.2 Stable Expression in CHO Cells

(273) Clones of the expression plasmids with sequence-verified nucleotide sequences were transfected into DHFR deficient CHO cells for eukaryotic expression of the constructs. Eukaryotic protein expression in DHFR deficient CHO cells was performed as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566. Gene amplification of the constructs was induced by increasing concentrations of methotrexate (MTX) to a final concentration of 20 nM MTX. After two passages of stationary culture the cells were grown in roller bottles with nucleoside-free HyQ PF CHO liquid soy medium (with 4.0 mM L-Glutamine with 0.1% Pluronic F-68; HyClone) for 7 days before harvest. The cells were removed by centrifugation and the supernatant containing the expressed protein was stored at 20 C.

Example D3

Epitope Clustering of Murine scFv-Fragments

(274) Cells transfected with human or murine BCMA, or with chimeric BCMA molecules were stained with crude, undiluted periplasmic extract containing scFv binding to human/macaque BCMA. Bound scFv were detected with 1 g/ml of an anti-FLAG antibody (Sigma F1804) and a R-PE-labeled anti-mouse Fc gamma-specific antibody (1:100; Dianova #115-116-071). All antibodies were diluted in PBS with 2% FCS. As negative control, cells were incubated with PBS/2% FCS instead of the periplasmic extract. The samples were measured by flow cytometry on a FACSCanto II instrument (Becton Dickinson) and analyzed by FlowJo software (Version 7.6).

Example D4

Procurement of Different Recombinant Forms of Soluble Human and Macaque BCMA

(275) The coding sequences of human and rhesus BCMA (as published in GenBank, accession numbers NM_001192 [human], XM_001106892 [rhesus]) coding sequences of human albumin, human Fc1 and murine albumin were used for the construction of artificial cDNA sequences encoding soluble fusion proteins of human and macaque BCMA respectively and human albumin, human IgG1 Fc and murine albumin respectively as well as soluble proteins comprising only the extracellular domains of BCMA. To generate the constructs for expression of the soluble human and macaque BCMA proteins, cDNA fragments were obtained by PCR mutagenesis of the full-length BCMA cDNAs described above and molecular cloning according to standard protocols.

(276) For the fusions with human albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and rhesus BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of human serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(277) For the fusions with murine IgG1, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of the hinge and Fc gamma portion of human IgG1, followed in frame by the coding sequence of a hexahistidine tag and a stop codon.

(278) For the fusions with murine albumin, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly4-Ser1-linker, followed in frame by the coding sequence of murine serum albumin, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(279) For the soluble extracellular domain constructs, the modified cDNA fragments were designed as to contain first a Kozak site for eukaryotic expression of the constructs followed by the coding sequence of the human and macaque BCMA proteins respectively, comprising amino acids 1 to 54 and 1 to 53 corresponding to the extracellular domain of human and rhesus BCMA, respectively, followed in frame by the coding sequence of an artificial Ser1-Gly1-linker, followed in frame by the coding sequence of a Flag tag, followed in frame by the coding sequence of a modified histidine tag (SGHHGGHHGGHH) and a stop codon.

(280) The cDNA fragments were also designed to introduce restriction sites at the beginning and at the end of the fragments. The introduced restriction sites, EcoRI at the 5 end and SalI at the 3 end, were utilized in the following cloning procedures. The cDNA fragments were cloned via EcoRI and SalI into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). The aforementioned procedures were all carried out according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y. (2001)).

Example D5

Biacore-Based Determination of Bispecific Antibody Affinity to Human and Macaque BCMA and CD3

(281) Biacore analysis experiments were performed using recombinant BCMA fusion proteins with human serum albumin (ALB) to determine BCMA target binding. For CD3 affinity measurements, recombinant fusion proteins having the N-terminal 27 amino acids of the CD3 epsilon (CD3e) fused to human antibody Fc portion were used. This recombinant protein exists in a human CD3e1-27 version and in a cynomolgous CD3e version, both bearing the epitope of the CD3 binder in the bispecific antibodies.

(282) In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 100 to 150 RU of the respective recombinant antigen using acetate buffer pH4.5 according to the manufacturer's manual. The bispecific antibody samples were loaded in five concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP running buffer (GE Healthcare). Flow rate was 30 to 35 l/min for 3 min, then HBS-EP running buffer was applied for 8 min again at a flow rate of 30 to 35 l/ml. Regeneration of the chip was performed using 10 mM glycine 0.5 M NaCl pH 2.45. Data sets were analyzed using BiaEval Software (see FIG. D4). In general two independent experiments were performed.

Example D6

Bispecific Binding and Interspecies Cross-Reactivity

(283) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS.

Example D7

Scatchard-Based Determination of Bispecific-Antibody Affinity to Human and Macaque BCMA

(284) For Scatchard analysis, saturation binding experiments are performed using a monovalent detection system developed at Micromet (anti-His Fab/Alexa 488) to precisely determine monovalent binding of the bispecific antibodies to the respective cell line.

(285) 210.sup.4 cells of the respective cell line (recombinantly human BCMA-expressing CHO cell line, recombinantly macaque BCMA-expressing CHO cell line) are incubated with each 50 l of a triplet dilution series (eight dilutions at 1:2) of the respective BCMA bispecific antibody starting at 100 nM followed by 16 h incubation at 4 C. under agitation and one residual washing step. Then, the cells are incubated for further 30 min with 30 l of an anti-His Fab/Alexa488 solution (Micromet; 30 g/ml). After one washing step, the cells are resuspended in 150 l FACS buffer containing 3.5% formaldehyde, incubated for further 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS Cantoll machine and FACS Diva software. Data are generated from two independent sets of experiments. Values are plotted as hyperbole binding curves. Respective Scatchard analysis is calculated to extrapolate maximal binding (Bmax). The concentrations of bispecific antibodies at half-maximal binding are determined reflecting the respective KDs. Values of triplicate measurements are plotted as hyperbolic curves. Maximal binding is determined using Scatchard evaluation and the respective KDs are calculated.

Example D8

Cytotoxic Activity

8.1 Chromium Release Assay with Stimulated Human T Cells

(286) Stimulated T cells enriched for CD8.sup.+ T cells were obtained as described below.

(287) A petri dish (145 mm diameter, Greiner bio-one GmbH, Kremsmunster) was coated with a commercially available anti-CD3 specific antibody (OKT3, Orthoclone) in a final concentration of 1 g/ml for 1 hour at 37 C. Unbound protein was removed by one washing step with PBS. 3-510.sup.7 human PBMC were added to the precoated petri dish in 120 ml of RPMI 1640 with stabilized glutamine/10% FCS/IL-2 20 U/ml (Proleukin, Chiron) and stimulated for 2 days. On the third day, the cells were collected and washed once with RPMI 1640. IL-2 was added to a final concentration of 20 U/ml and the cells were cultured again for one day in the same cell culture medium as above.

(288) CD8.sup.+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4.sup.+ T cells and CD56.sup.+ NK cells using Dynal-Beads according to the manufacturer's protocol.

(289) Macaque or human BCMA-transfected CHO target cells were washed twice with PBS and labeled with 11.1 MBq .sup.51Cr in a final volume of 100 l RPMI with 50% FCS for 60 minutes at 37 C. Subsequently, the labeled target cells were washed 3 times with 5 ml RPMI and then used in the cytotoxicity assay. The assay was performed in a 96-well plate in a total volume of 200 l supplemented RPMI with an E:T ratio of 10:1. A starting concentration of 0.01-1 g/ml of purified bispecific antibody and threefold dilutions thereof were used. Incubation time for the assay was 18 hours. Cytotoxicity was determined as relative values of released chromium in the supernatant relative to the difference of maximum lysis (addition of Triton-X) and spontaneous lysis (without effector cells). All measurements were carried out in quadruplicates. Measurement of chromium activity in the supernatants was performed in a Wizard 3 gamma counter (Perkin Elmer Life Sciences GmbH, Kln, Germany). Analysis of the results was carried out with Prism 5 for Windows (version 5.0, GraphPad Software Inc., San Diego, Calif., USA). EC50 values calculated by the analysis program from the sigmoidal dose response curves were used for comparison of cytotoxic activity (see FIG. D5).

8.2 FACS-Based Cytotoxicity Assay with Unstimulated Human PBMC

(290) Isolation of Effector Cells

(291) Human peripheral blood mononuclear cells (PBMC) were prepared by Ficoll density gradient centrifugation from enriched lymphocyte preparations (buffy coats), a side product of blood banks collecting blood for transfusions. Buffy coats were supplied by a local blood bank and PBMC were prepared on the same day of blood collection. After Ficoll density centrifugation and extensive washes with Dulbecco's PBS (Gibco), remaining erythrocytes were removed from PBMC via incubation with erythrocyte lysis buffer (155 mM NH.sub.4Cl, 10 mM KHCO.sub.3, 100 M EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100g. Remaining lymphocytes mainly encompass B and T lymphocytes, NK cells and monocytes. PBMC were kept in culture at 37 C./5% CO.sub.2 in RPMI medium (Gibco) with 10% FCS (Gibco).

(292) Depletion of CD14.sup.+ and CD56.sup.+ Cells

(293) For depletion of CD14.sup.+ cells, human CD14 MicroBeads (Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted and centrifuged for 10 min at room temperature with 300g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 L/10.sup.7 cells; PBS (Invitrogen, #20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA (Sigma-Aldrich, #E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20 L/10.sup.7 cells) were added and incubated for 15 min at 4-8 C. The cells were washed with MACS isolation buffer (1-2 mL/10.sup.7 cells). After centrifugation (see above), supernatant was discarded and cells resuspended in MACS isolation buffer (500 L/10.sup.8 cells). CD14/CD56 negative cells were then isolated using LS Columns (Miltenyi Biotec, #130-042-401). PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium i.e. RPMI1640 (Biochrom AG, #FG1215) supplemented with 10% FBS (Biochrom AG, #S0115), 1 non-essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, #L1613), 1 mM sodium pyruvate (Biochrom AG, #L0473) and 100 U/mL penicillin/streptomycin (Biochrom AG, #A2213) at 37 C. in an incubator until needed.

(294) Target Cell Labeling

(295) For the analysis of cell lysis in flow cytometry assays, the fluorescent membrane dye DiOC.sub.13 (DiO) (Molecular Probes, #V22886) was used to label human BCMA- or macaque BCMA-transfected CHO cells as target cells and distinguish them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10.sup.6 cell/mL in PBS containing 2% (v/v) FBS and the membrane dye DiO (5 L/10.sup.6 cells). After incubation for 3 min at 37 C., cells were washed twice in complete RPMI medium and the cell number adjusted to 1.2510.sup.5 cells/mL. The vitality of cells was determined using 0.5% (v/v) isotonic EosinG solution (Roth, #45380).

(296) Flow Cytometry Based Analysis

(297) This assay was designed to quantify the lysis of macaque or human BCMA-transfected CHO cells in the presence of serial dilutions of BCMA bispecific antibodies.

(298) Equal volumes of DiO-labeled target cells and effector cells (i.e., PBMC w/o CD14.sup.+ cells) were mixed, resulting in an E:T cell ratio of 10:1. 160 L of this suspension were transferred to each well of a 96-well plate. 40 L of serial dilutions of the BCMA bispecific antibodies and a negative control bispecific (an CD3-based bispecific antibody recognizing an irrelevant target antigen) or RPMI complete medium as an additional negative control were added. The bispecific antibody-mediated cytotoxic reaction proceeded for 48 hours in a 7% CO.sub.2 humidified incubator. Then cells were transferred to a new 96-well plate and loss of target cell membrane integrity was monitored by adding propidium iodide (PI) at a final concentration of 1 g/mL. PI is a membrane impermeable dye that normally is excluded from viable cells, whereas dead cells take it up and become identifiable by fluorescent emission.

(299) Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson).

(300) Target cells were identified as DiO-positive cells. PI-negative target cells were classified as living target cells. Percentage of cytotoxicity was calculated according to the following formula:

(301) $\mathrm{Cytotoxicity}\left[\%\right]=\frac{n_{\mathrm{dead}\mathrm{target}\mathrm{cells}}}{n_{\mathrm{target}\mathrm{cells}}}100$$n=\mathrm{number}\mathrm{of}\mathrm{events}$

(302) Using GraphPad Prism 5 software (Graph Pad Software, San Diego), the percentage of cytotoxicity was plotted against the corresponding bispecific antibody concentrations. Dose response curves were analyzed with the four parametric logistic regression models for evaluation of sigmoid dose response curves with fixed hill slope and EC50 values were calculated.

Example D9

Exclusion of Cross-Reactivity with BAFF-Receptor

(303) For flow cytometry, 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 l of purified bispecific molecules at a concentration of 5 g/ml. The cells were washed twice in PBS with 2% FCS and binding of the constructs was detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in 50 l PBS with 2% FCS). After washing, bound PentaHis antibodies were detected with an Fc gamma-specific antibody (Dianova) conjugated to phycoerythrin, diluted 1:100 in PBS with 2% FCS. Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed by FACSDiva software (both from Becton Dickinson). The bispecific binders were shown to not be cross-reactive with BAFF receptor.

Example D10

Cytotoxic Activity

(304) The potency of human-like BCMA bispecific antibodies in redirecting effector T cells against BCMA-expressing target cells is analyzed in five additional in vitro cytotoxicity assays:

(305) 1. The potency of BCMA bispecific antibodies in redirecting stimulated human effector T cells against a BCMA-positive (human) tumor cell line is measured in a 51-chromium release assay.

(306) 2. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against human BCMA-transfected CHO cells is measured in a FACS-based cytotoxicity assay.

(307) 3. The potency of BCMA bispecific antibodies in redirecting the T cells in unstimulated human PBMC against a BCMA-positive (human) tumor cell line is measured in a FACS-based cytotoxicity assay.

(308) 4. For confirmation that the cross-reactive BCMA bispecific antibodies are capable of redirecting macaque T cells against macaque BCMA-transfected CHO cells, a FACS-based cytotoxicity assay is performed with a macaque T cell line as effector T cells.

(309) 5. The potency gap between monomeric and dimeric forms of BCMA bispecific antibodies is determined in a 51-chromium release assay using human BCMA-transfected CHO cells as target cells and stimulated human T cells as effector cells.

(310) TABLE-US-00015 SEQ ID Desig- Desig- Format/ NO nation nation source Type Sequence 1 BCMA-1 BC5G9 VHCDR1 aa NYDMA 91-C7- B10 2 BCMA-1 BC5G9 VHCDR2 aa SIITSGDATYYRDSVKG 91-C7- B10 3 BCMA-1 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-C7- B10 4 BCMA-1 BC5G9 VLCDR1 aa KASQSVGINVD 91-C7- B10 5 BCMA-1 BC5G9 VLCDR2 aa GASNRHT 91-C7- B10 6 BCMA-1 BC5G9 VLCDR3 aa LQYGSIPFT 91-C7- B10 7 BCMA-1 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-C7- FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS B10 8 BCMA-1 BC5G9 VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-C7- GREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK B10 9 BCMA-1 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-C7- FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG B10 GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 10 BCMA-1 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR HLx 91-C7- specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL B10 molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 11 BCMA-2 BC5G9 VHCDR1 aa NYDMA 91-C7- D8 12 BCMA-2 BC5G9 VHCDR2 aa SIITSGDMTYYRDSVKG 91-C7- D8 13 BCMA-2 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-C7- D8 14 BCMA-2 BC5G9 VLCDR1 aa KASQSVGINVD 91-C7- D8 15 BCMA-2 BC5G9 VLCDR2 aa GASNRHT 91-C7- D8 16 BCMA-2 BC5G9 VLCDR3 aa LQYGSIPFT 91-C7- D8 17 BCMA-2 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-C7- FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS D8 18 BCMA-2 BC5G9 VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-C7- GREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK D8 19 BCMA-2 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-C7- FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG D8 GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 20 BCMA-2 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR HLx 91-C7- specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL D8 molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 21 BCMA-3 BC5G9 VHCDR1 aa NYDMA 91-E4- B10 22 BCMA-3 BC5G9 VHCDR2 aa SIITSGDATYYRDSVKG 91-E4- B10 23 BCMA-3 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-E4- B10 24 BCMA-3 BC5G9 VLCDR1 aa KASQSVGINVD 91-E4- B10 25 BCMA-3 BC5G9 VLCDR2 aa GASNRHT 91-E4- B10 26 BCMA-3 BC5G9 VLCDR3 aa LQYGSIPFT 91-E4- B10 27 BCMA-3 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-E4- FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS B10 28 BCMA-3 BC5G9 VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-E4- GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK B10 29 BCMA-3 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-E4- FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG B10 GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 30 BCMA-3 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR HLx 91-E4- specific FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL B10 molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 31 BCMA-4 BC5G9 VHCDR1 aa NYDMA 91-E4- D8 32 BCMA-4 BC5G9 VHCDR2 aa SIITSGDMTYYRDSVKG 91-E4- D8 33 BCMA-4 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-E4- D8 34 BCMA-4 BC5G9 VLCDR1 aa KASQSVGINVD 91-E4- D8 35 BCMA-4 BC5G9 VLCDR2 aa GASNRHT 91-E4- D8 36 BCMA-4 BC5G9 VLCDR3 aa LQYGSIPFT 91-E4- D8 37 BCMA-4 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-E4- FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS D8 38 BCMA-4 BC5G9 VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-E4- GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK D8 39 BCMA-4 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-E4- FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG D8 GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 40 BCMA-4 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR HLx 91-E4- specific FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL D8 molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 41 BCMA-5 BC5G9 VHCDR1 aa NYDMA 91-D2- B10 42 BCMA-5 BC5G9 VHCDR2 aa SIITSGDATYYRDSVKG 91-D2- B10 43 BCMA-5 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-D2- B10 44 BCMA-5 BC5G9 VLCDR1 aa KASQSVGINVD 91-D2- B10 45 BCMA-5 BC5G9 VLCDR2 aa GASNRHT 91-D2- B10 46 BCMA-5 BC5G9 VLCDR3 aa LQYGSIPFT 91-D2- B10 47 BCMA-5 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-D2- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS B10 48 BCMA-5 BC5G9 VL aa EIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-D2- GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK B10 49 BCMA-5 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 91-D2- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG B10 GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 50 BCMA-5 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR HLx 91-D2- specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL B10 molecule GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 51 BCMA-6 BC5G9 VHCDR1 aa NYDMA 91-D2- D8 52 BCMA-6 BC5G9 VHCDR2 aa SIITSGDMTYYRDSVKG 91-D2- D8 53 BCMA-6 BC5G9 VHCDR3 aa HDYYDGSYGFAY 91-D2- D8 54 BCMA-6 BC5G9 VLCDR1 aa KASQSVGINVD 91-D2- D8 55 BCMA-6 BC5G9 VLCDR2 aa GASNRHT 91-D2- D8 56 BCMA-6 BC5G9 VLCDR3 aa LQYGSIPFT 91-D2- D8 57 BCMA-6 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-D2- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS D8 58 BCMA-6 BC5G9 VL aa EIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-D2- GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK D8 59 BCMA-6 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 91-D2- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG D8 GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 60 BCMA-6 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR HLx 91-D2- specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL D8 molecule GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 61 BCMA-7 BC5G9 VHCDR1 aa NYDMA 92-E10- B10 62 BCMA-7 BC5G9 VHCDR2 aa SIITSGDATYYRDSVKG 92-E10- B10 63 BCMA-7 BC5G9 VHCDR3 aa HDYYDGSYGFAY 92-E10- B10 64 BCMA-7 BC5G9 VLCDR1 aa KASQSVGINVD 92-E10- B10 65 BCMA-7 BC5G9 VLCDR2 aa GASNRHT 92-E10- B10 66 BCMA-7 BC5G9 VLCDR3 aa LQYGSIPFT 92-E10- B10 67 BCMA-7 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 92-E10- FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS B10 68 BCMA-7 BC5G9 VL aa EIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 92-E10- GTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK B10 69 BCMA-7 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR 92-E10- FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG B10 GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK 70 BCMA-7 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDATYYRDSVKGR HLx 92- specific FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E10B10 molecule GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 71 BCMA-8 BC5G9 VHCDR1 aa NYDMA 92-E10- D8 72 BCMA-8 BC5G9 VHCDR2 aa SIITSGDMTYYRDSVKG 92-E10- D8 73 BCMA-8 BC5G9 VHCDR3 aa HDYYDGSYGFAY 92-E10- D8 74 BCMA-8 BC5G9 VLCDR1 aa KASQSVGINVD 92-E10- D8 75 BCMA-8 BC5G9 VLCDR2 aa GASNRHT 92-E10- D8 76 BCMA-8 BC5G9 VLCDR3 aa LQYGSIPFT 92-E10- D8 77 BCMA-8 BC5G9 VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 92-E10- FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS D8 78 BCMA-8 BC5G9 VL aa EIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 92-E10- GTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK D8 79 BCMA-8 BC5G9 scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR 92-E10- FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG D8 GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK 80 BCMA-8 BC5G9 bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGDMTYYRDSVKGR HLx 92-E10- specific FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL D8 molecule GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS HLx GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 81 BCMA-9 BCH1 VHCDR1 aa NYWIH 38-D2- A4 82 BCMA-9 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 38-D2- A4 83 BCMA-9 BCH1 VHCDR3 aa SSYYYDGSLFAS 38-D2- A4 84 BCMA-9 BCH1 VLCDR1 aa RSSQSIVHSNGNTYLY 38-D2- A4 85 BCMA-9 BCH1 VLCDR2 aa RVSNRFS 38-D2- A4 86 BCMA-9 BCH1 VLCDR3 aa FQGSTLPFT 38-D2- A4 87 BCMA-9 BCH1 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-D2- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS A4 88 BCMA-9 BCH1 VL aa DIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 38-D2- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK A4 89 BCMA-9 BCH1 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-D2- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG A4 GSDIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK 90 BCMA-9 BCH1 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK HLx 38-D2- specific VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL A4 molecule GSDIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 91 BCMA-10 BCH1 VHCDR1 aa NYWIH 38-D2- F12 92 BCMA-10 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 38-D2- F12 93 BCMA-10 BCH1 VHCDR3 aa SSYYYDGSLFAS 38-D2- F12 94 BCMA-10 BCH1 VLCDR1 aa RSSQSIVHSNGNTYLY 38-D2- F12 95 BCMA-10 BCH1 VLCDR2 aa RVSNRFS 38-D2- F12 96 BCMA-10 BCH1 VLCDR3 aa FQGSHLPFT 38-D2- F12 97 BCMA-10 BCH1 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-D2- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS F12 98 BCMA-10 BCH1 VL aa DIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 38-D2- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK F12 99 BCMA-10 BCH1 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-D2- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG F12 GSDIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK 100 BCMA-10 BCH1 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK HLx 38-D2- specific VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL F12 molecule GSDIVMTQTPLSLSVSPGQPASISCRSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 101 BCMA-11 BCH1 VHCDR1 aa NYWIH 38-C1- A4 102 BCMA-11 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 38-C1- A4 103 BCMA-11 BCH1 VHCDR3 aa SSYYYDGSLFAS 38-C1- A4 104 BCMA-11 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 38-C1- A4 105 BCMA-11 BCH1 VLCDR2 aa RVSNRFS 38-C1- A4 106 BCMA-11 BCH1 VLCDR3 aa FQGSTLPFT 38-C1- A4 107 BCMA-11 BCH1 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-C1- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS A4 108 BCMA-11 BCH1 VL aa DIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 38-C1- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK A4 109 BCMA-11 BCH1 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-C1- A4 VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK 110 BCMA-11 BCH1 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK HLx 38-C1- specific VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL A4 molecule GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 111 BCMA-12 BCH1 VHCDR1 aa NYWIH 38-C1- F12 112 BCMA-12 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 38-C1- F12 113 BCMA-12 BCH1 VHCDR3 aa SSYYYDGSLFAS 38-C1- F12 114 BCMA-12 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 38-C1- F12 115 BCMA-12 BCH1 VLCDR2 aa RVSNRFS 38-C1- F12 116 BCMA-12 BCH1 VLCDR3 aa FQGSHLPFT 38-C1- F12 117 BCMA-12 BCH1 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-C1- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS F12 118 BCMA-12 BCH1 VL aa DIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 38-C1- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK F12 119 BCMA-12 BCH1 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK 38-C1- VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG F12 GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK 120 BCMA-12 BCH1 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGK HLx 38-C1- specific VTITRDTSASTAYMELSSLTSEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL F12 molecule GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 121 BCMA-13 BCH1 VHCDR1 aa NYWIH 39-B2- A4 122 BCMA-13 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 39-B2- A4 123 BCMA-13 BCH1 VHCDR3 aa SSYYYDGSLFAS 39-B2- A4 124 BCMA-13 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 39-B2- A4 125 BCMA-13 BCH1 VLCDR2 aa RVSNRFS 39-B2- A4 126 BCMA-13 BCH1 VLCDR3 aa FQGSTLPFT 39-B2- A4 127 BCMA-13 BCH1 VH aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR 39-B2- VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS A4 128 BCMA-13 BCH1 VL aa DIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 39-B2- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK A4 129 BCMA-13 BCH1 scFv aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR 39-B2- VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG A4 GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK 130 BCMA-13 BCH1 bi- aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR HLx 39-B2- specific VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL A4 molecule GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 131 BCMA-14 BCH1 VHCDR1 aa NYWIH 39-B2- F12 132 BCMA-14 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 39-B2- F12 133 BCMA-14 BCH1 VHCDR3 aa SSYYYDGSLFAS 39-B2- F12 134 BCMA-14 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 39-B2- F12 135 BCMA-14 BCH1 VLCDR2 aa RVSNRFS 39-B2- F12 136 BCMA-14 BCH1 VLCDR3 aa FQGSHLPFT 39-B2- F12 137 BCMA-14 BCH1 VH aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR 39-B2- VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSS F12 138 BCMA-14 BCH1 VL aa DIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 39-B2- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK F12 139 BCMA-14 BCH1 scFv aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR 39-B2- VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG F12 GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK 140 BCMA-14 BCH1 bi- aa QVQLVQSGAVVAKPGASVKVSCKASGYTFTNYWIHWVKQAPGQRLEWMGAIYPGNSDTHYNQKFQGR HLx 39-B2- specific VTLTTDTSASTAYMELSSLRNEDTAVYYCTRSSYYYDGSLFASWGQGTLVTVSSGGGGSGGGGSGGG CD3HL F12 molecule GSDIVMTQTPLSLSVTPGQQASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 141 BCMA-15 BCH1 VHCDR1 aa SYWIH 39-C9- A4 142 BCMA-15 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 39-C9- A4 143 BCMA-15 BCH1 VHCDR3 aa SSYYYDGSLFAD 39-C9- A4 144 BCMA-15 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 39-C9- A4 145 BCMA-15 BCH1 VLCDR2 aa RVSNRFS 39-C9- A4 146 BCMA-15 BCH1 VLCDR3 aa FQGSTLPFT 39-C9- A4 147 BCMA-15 BCH1 VH aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR 39-C9- VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSS A4 148 BCMA-15 BCH1 VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 39-C9- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK A4 149 BCMA-15 BCH1 scFv aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR 39-C9- VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSSGGGGSGGGGSGGG A4 GSDIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIK 150 BCMA-15 BCH1 bi- aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR HLx 39-C9- specific VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSSGGGGSGGGGSGGG CD3HL A4 molecule GSDIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSTLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 151 BCMA-16 BCH1 VHCDR1 aa SYWIH 39-C9- F12 152 BCMA-16 BCH1 VHCDR2 aa AIYPGNSDTHYNQKFQG 39-C9- F12 153 BCMA-16 BCH1 VHCDR3 aa SSYYYDGSLFAD 39-C9- F12 154 BCMA-16 BCH1 VLCDR1 aa KSSQSIVHSNGNTYLY 39-C9- F12 155 BCMA-16 BCH1 VLCDR2 aa RVSNRFS 39-C9- F12 156 BCMA-16 BCH1 VLCDR3 aa FQGSHLPFT 39-C9- F12 157 BCMA-16 BCH1 VH aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR 39-C9- VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSS F12 158 BCMA-16 BCH1 VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPDRF 39-C9- SGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK F12 159 BCMA-16 BCH1 scFv aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR 39-C9- VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSSGGGGSGGGGSGGG F12 GSDIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIK 160 BCMA-16 BCH1 bi- aa QVQLVQSGAEVKKPGTSVKVSCKASGYTFTSYWIHWVKQAPGQRLEWIGAIYPGNSDTHYNQKFQGR HLx 39-C9- specific VTLTRDTSASTAYMELSSLRSEDSAVYYCTRSSYYYDGSLFADWGQGTLVTVSSGGGGSGGGGSGGG CD3HL F12 molecule GSDIVMTQTPLSLSVTPGQPASISCKSSQSIVHSNGNTYLYWYLQKPGQPPQLLIYRVSNRFSGVPD HLx RFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHLPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQP CD3 GGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA HL YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 161 BCMA-17 BCC3 VHCDR1 aa NFDMA 33-D7- E6 162 BCMA-17 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-D7- E6 163 BCMA-17 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-D7- E6 164 BCMA-17 BCC3 VLCDR1 aa RASQGISNYLN 33-D7- E6 165 BCMA-17 BCC3 VLCDR2 aa YTSNLQS 33-D7- E6 166 BCMA-17 BCC3 VLCDR3 aa QQYDISSYT 33-D7- E6 167 BCMA-17 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-D7- FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6 168 BCMA-17 BCC3 VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-D7- GTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK E6 169 BCMA-17 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-D7- FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6 GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK 170 BCMA-17 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR HLx 33-D7- specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 171 BCMA-18 BCC3 VHCDR1 aa NFDMA 33-D7- E6B1 172 BCMA-18 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-D7- E6B1 173 BCMA-18 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-D7- E6B1 174 BCMA-18 BCC3 VLCDR1 aa RASQGISNYLN 33-D7- E6B1 175 BCMA-18 BCC3 VLCDR2 aa YTSNLQS 33-D7- E6B1 176 BCMA-18 BCC3 VLCDR3 aa MGQTISSYT 33-D7- E6B1 177 BCMA-18 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-D7- FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6B1 178 BCMA-18 BCC3 VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-D7- GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK E6B1 179 BCMA-18 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-D7- FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6B1 GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 180 BCMA-18 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR HLx 33-D7- specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6B1 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 181 BCMA-19 BCC3 VHCDR1 aa NFDMA 33-F8- E6 182 BCMA-19 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-F8- E6 183 BCMA-19 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-F8- E6 184 BCMA-19 BCC3 VLCDR1 aa RASQGISNYLN 33-F8- E6 185 BCMA-19 BCC3 VLCDR2 aa YTSNLQS 33-F8- E6 186 BCMA-19 BCC3 VLCDR3 aa QQYDISSYT 33-F8- E6 187 BCMA-19 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F8- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6 188 BCMA-19 BCC3 VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-F8- GTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK E6 189 BCMA-19 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F8- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6 GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK 190 BCMA-19 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR HLx 33-F8- specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 191 BCMA-20 BCC3 VHCDR1 aa NFDMA 33-F8- E6B1 192 BCMA-20 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-F8- E6B1 193 BCMA-20 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-F8- E6B1 194 BCMA-20 BCC3 VLCDR1 aa RASQGISNYLN 33-F8- E6B1 195 BCMA-20 BCC3 VLCDR2 aa YTSNLQS 33-F8- E6B1 196 BCMA-20 BCC3 VLCDR3 aa MGQTISSYT 33-F8- E6B1 197 BCMA-20 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F8- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6B1 198 BCMA-20 BCC3 VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-F8- GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK E6B1 199 BCMA-20 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F8- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6B1 GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 200 BCMA-20 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR HLx 33-F8- specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6B1 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 201 BCMA-21 BCC3 VHCDR1 aa NFDMA 33-F9- E6 202 BCMA-21 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-F9- E6 203 BCMA-21 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-F9- E6 204 BCMA-21 BCC3 VLCDR1 aa RASQGISNYLN 33-F9- E6 205 BCMA-21 BCC3 VLCDR2 aa YTSNLQS 33-F9- E6 206 BCMA-21 BCC3 VLCDR3 aa QQYDISSYT 33-F9- E6 207 BCMA-21 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F9- FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6 208 BCMA-21 BCC3 VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-F9- GTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK E6 209 BCMA-21 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR 33-F9- FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6 GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIK 210 BCMA-21 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYADSVKGR HLx 33-F9- specific FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6 molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCQQYDISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 211 BCMA-22 BCC3 VHCDR1 aa NFDMA 33-F9- E6B1-E 212 BCMA-22 BCC3 VHCDR2 aa SITTGADHAIYAESVKG 33-F9- E6B1-E 213 BCMA-22 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-F9- E6B1-E 214 BCMA-22 BCC3 VLCDR1 aa RASQGISNYLN 33-F9- E6B1-E 215 BCMA-22 BCC3 VLCDR2 aa YTSNLQS 33-F9- E6B1-E 216 BCMA-22 BCC3 VLCDR3 aa MGQTISSYT 33-F9- E6B1-E 217 BCMA-22 BCC3 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYAESVKGR 33-F9- FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6B1-E 218 BCMA-22 BCC3 VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-F9- GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK E6B1-E 219 BCMA-22 BCC3 scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYAESVKGR 33-F9- FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6B1-E GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 220 BCMA-22 BCC3 bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGADHAIYAESVKGR HLx 33-F9- specific FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6B1-E molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 221 BCMA-23 BCC3 VHCDR1 aa NFDMA 33-F10- E6B1 222 BCMA-23 BCC3 VHCDR2 aa SITTGADHAIYADSVKG 33-F10- E6B1 223 BCMA-23 BCC3 VHCDR3 aa HGYYDGYHLFDY 33-F10- E6B1 224 BCMA-23 BCC3 VLCDR1 aa RASQGISNYLN 33-F10- E6B1 225 BCMA-23 BCC3 VLCDR2 aa YTSNLQS 33-F10- E6B1 226 BCMA-23 BCC3 VLCDR3 aa MGQTISSYT 33-F10- E6B1 227 BCMA-23 BCC3 VH aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGADHAIYADSVKGR 33-F10- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS E6B1 228 BCMA-23 BCC3 VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-F10- GTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK E6B1 229 BCMA-23 BCC3 scFv aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGADHAIYADSVKGR 33-F10- FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG E6B1 GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 230 BCMA-23 BCC3 bi- aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGADHAIYADSVKGR HLx 33-F10- specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL E6B1 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HLx GSGTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 231 BCMA-24 BCB6 VHCDR1 aa DYYIN 64-H5- A4 232 BCMA-24 BCB6 VHCDR2 aa WIYFASGNSEYNQKFTG 64-H5- A4 233 BCMA-24 BCB6 VHCDR3 aa LYDYDWYFDV 64-H5- A4 234 BCMA-24 BCB6 VLCDR1 aa KSSQSLVHSNGNTYLH 64-H5- A4 235 BCMA-24 BCB6 VLCDR2 aa KVSNRFS 64-H5- A4 236 BCMA-24 BCB6 VLCDR3 aa AETSHVPWT 64-H5- A4 237 BCMA-24 BCB6 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 64-H5- VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS A4 238 BCMA-24 BCB6 VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF 64-H5- SGSGSGTDFTLKINRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK A4 239 BCMA-24 BCB6 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 64-H5- VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS A4 DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKINRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 240 BCMA-24 BCB6 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx 64-H5- specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL A4 molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF HLx SGSGSGTDFTLKINRVEAEDVGVYYCAETSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG CD3 SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL HL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 241 BCMA-25 BCB6 VHCDR1 aa DYYIN 64-H5- H9 242 BCMA-25 BCB6 VHCDR2 aa WIYFASGNSEYNQKFTG 64-H5- H9 243 BCMA-25 BCB6 VHCDR3 aa LYDYDWYFDV 64-H5- H9 244 BCMA-25 BCB6 VLCDR1 aa KSSQSLVHSNGNTYLH 64-H5- H9 245 BCMA-25 BCB6 VLCDR2 aa KVSNRFS 64-H5- H9 246 BCMA-25 BCB6 VLCDR3 aa LTTSHVPWT 64-H5- H9 247 BCMA-25 BCB6 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 64-H5- VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS H9 248 BCMA-25 BCB6 VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF 64-H5- SGSGSGTDFTLKINRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK H9 249 BCMA-25 BCB6 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 64-H5- VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS H9 DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKINRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 250 BCMA-25 BCB6 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx 64-H5- specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL H9 molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF HLx SGSGSGTDFTLKINRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG CD3 SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL HL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 251 BCMA-26 BCB6 VHCDR1 aa DYYIN 65-B5-A4 252 BCMA-26 BCB6 VHCDR2 aa WIYFASGNSEYNQKFTG 65-B5-A4 253 BCMA-26 BCB6 VHCDR3 aa LYDYDWYFDV 65-B5-A4 254 BCMA-26 BCB6 VLCDR1 aa KSSQSLVHSNGNTYLH 65-B5-A4 255 BCMA-26 BCB6 VLCDR2 aa KVSNRFS 65-B5-A4 256 BCMA-26 BCB6 VLCDR3 aa AETSHVPWT 65-B5-A4 257 BCMA-26 BCB6 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 65-B5-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 258 BCMA-26 BCB6 VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF 65-B5-A4 SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 259 BCMA-26 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR B5-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 260 BCMA-26 BCB665- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx B5-A4HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 261 BCMA-27 BCB665- VHCDR1 aa DYYIN B5-H9 262 BCMA-27 BCB665- VHCDR2 aa WIYFASGNSEYNQKFTG B5-H9 263 BCMA-27 BCB665- VHCDR3 aa LYDYDWYFDV B5-H9 264 BCMA-27 BCB665- VLCDR1 aa KSSQSLVHSNGNTYLH B5-H9 265 BCMA-27 BCB665- VLCDR2 aa KVSNRFS B5-H9 266 BCMA-27 BCB665- VLCDR3 aa LTTSHVPWT B5-H9 267 BCMA-27 BCB665- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR B5-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 268 BCMA-27 BCB665- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF B5-H9 SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 269 BCMA-27 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR B5-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 270 BCMA-27 BCB665- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx B5-H9HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 271 BCMA-28 BCB665- VHCDR1 aa DYYIN H7-A4 272 BCMA-28 BCB665- VHCDR2 aa WIYFASGNSEYNQKFTG H7-A4 273 BCMA-28 BCB665- VHCDR3 aa LYDYDWYFDV H7-A4 274 BCMA-28 BCB665- VLCDR1 aa KSSQSLVHSNGNTYLH H7-A4 275 BCMA-28 BCB665- VLCDR2 aa KVSNRFS H7-A4 276 BCMA-28 BCB665- VLCDR3 aa AETSHVPWT H7-A4 277 BCMA-28 BCB665- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H7-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 278 BCMA-28 BCB665- VL aa DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF H7-A4 SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 279 BCMA-28 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H7-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 280 BCMA-28 BCB665- bi aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx H7-A4HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 281 BCMA-29 BCB665- VHCDR1 aa DYYIN H7-H9 282 BCMA-29 BCB665- VHCDR2 aa WIYFASGNSEYNQKFTG H7-H9 283 BCMA-29 BCB665- VHCDR3 aa LYDYDWYFDV H7-H9 284 BCMA-29 BCB665- VLCDR1 aa KSSQSLVHSNGNTYLH H7-H9 285 BCMA-29 BCB665- VLCDR2 aa KVSNRFS H7-H9 286 BCMA-29 BCB665- VLCDR3 aa LTTSHVPWT H7-H9 287 BCMA-29 BCB665- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H7-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 288 BCMA-29 BCB665- VL aa DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF H7-H9 SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 289 BCMA-29 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H7-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 290 BCMA-29 BCB665- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx H7-H9HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVSPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 291 BCMA-30 BCB665- VHCDR1 aa DYYIN H8-A4 292 BCMA-30 BCB665- VHCDR2 aa WIYFASGNSEYNQKFTG H8-A4 293 BCMA-30 BCB665- VHCDR3 aa LYDYDWYFDV H8-A4 294 BCMA-30 BCB665- VLCDR1 aa KSSQSLVHSNGNTYLH H8-A4 295 BCMA-30 BCB665- VLCDR2 aa KVSNRFS H8-A4 296 BCMA-30 BCB665- VLCDR3 aa AETSHVPWT H8-A4 297 BCMA-30 BCB665- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H8-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 298 BCMA-30 BCB665- VL aa DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF H8-A4 SGSGSGADFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 299 BCMA-30 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H8-A4 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGADFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIK 300 BCMA-30 BCB665- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx H8-A4HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGADFTLKISRVEAEDVGVYYCAETSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 301 BCMA-31 BCB665- VHCDR1 aa DYYIN H8-H9 302 BCMA-31 BCB665- VHCDR2 aa WIYFASGNSEYNQKFTG H8-H9 303 BCMA-31 BCB665- VHCDR3 aa LYDYDWYFDV H8-H9 304 BCMA-31 BCB665- VLCDR1 aa KSSQSLVHSNGNTYLH H8-H9 305 BCMA-31 BCB665- VLCDR2 aa KVSNRFS H8-H9 306 BCMA-31 BCB665- VLCDR3 aa LTTSHVPWT H8-H9 307 BCMA-31 BCB665- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H8-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 308 BCMA-31 BCB665- VL aa DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF H8-H9 SGSGSGADFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 309 BCMA-31 BCB665- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR H8-H9 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGADFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIK 310 BCMA-31 BCB665- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx H8-H9HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGEPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGADFTLKISRVEAEDVGVYYCLTTSHVPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 311 BCMA-32 BCA727- VHCDR1 aa NHIIH A6-G7 312 BCMA-32 BCA727- VHCDR2 aa YINPYPGYHAYNEKFQG A6-G7 313 BCMA-32 BCA727- VHCDR3 aa DGYYRDTDVLDY A6-G7 314 BCMA-32 BCA727- VLCDR1 aa QASQDISNYLN A6-G7 315 BCMA-32 BCA727- VLCDR2 aa YTSRLHT A6-G7 316 BCMA-32 BCA727- VLCDR3 aa QQGNTLPWT A6-G7 317 BCMA-32 BCA727- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR A6-G7 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSS 318 BCMA-32 BCA727- VL aa DIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS A6-G7 GTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 319 BCMA-32 BCA727- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR A6-G7 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 320 BCMA-32 BCA727- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR HLx A6-G7HL specific ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 321 BCMA-33 BCA727- VHCDR1 aa NHIIH A6-H11 322 BCMA-33 BCA727- VHCDR2 aa YINPYDGWGDYNEKFQG A6-H11 323 BCMA-33 BCA727- VHCDR3 aa DGYYRDADVLDY A6-H11 324 BCMA-33 BCA727- VLCDR1 aa QASQDISNYLN A6-H11 325 BCMA-33 BCA727- VLCDR2 aa YTSRLHT A6-H11 326 BCMA-33 BCA727- VLCDR3 aa QQGNTLPWT A6-H11 327 BCMA-33 BCA727- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR A6-H11 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSS 328 BCMA-33 BCA727- VL aa DIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS A6-H11 GTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 329 BCMA-33 BCA727- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR A6-H11 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 330 BCMA-33 BCA727- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR HLx A6-H11HL specific ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 331 BCMA-34 BCA727- VHCDR1 aa NHIIH C4-G7 332 BCMA-34 BCA727- VHCDR2 aa YINPYPGYHAYNEKFQG C4-G7 333 BCMA-34 BCA727- VHCDR3 aa DGYYRDTDVLDY C4-G7 334 BCMA-34 BCA727- VLCDR1 aa QASQDISNYLN C4-G7 335 BCMA-34 BCA727- VLCDR2 aa YTSRLHT C4-G7 336 BCMA-34 BCA727- VLCDR3 aa QQGNTLPWT C4-G7 337 BCMA-34 BCA727- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR C4-G7 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSS 338 BCMA-34 BCA727- VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS C4-G7 GTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 339 BCMA-34 BCA727- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR C4-G7 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 340 BCMA-34 BCA727- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYHAYNEKFQGR HLx C4-G7HL specific ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 341 BCMA-35 BCA727- VHCDR1 aa NHIIH C4-H11 342 BCMA-35 BCA727- VHCDR2 aa YINPYDGWGDYNEKFQG C4-H11 343 BCMA-35 BCA727- VHCDR3 aa DGYYRDADVLDY C4-H11 344 BCMA-35 BCA727- VLCDR1 aa QASQDISNYLN C4-H11 345 BCMA-35 BCA727- VLCDR2 aa YTSRLHT C4-H11 346 BCMA-35 BCA727- VLCDR3 aa QQGNTLPWT C4-H11 347 BCMA-35 BCA727- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR C4-H11 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSS 348 BCMA-35 BCA727- VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS C4-H11 GTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 349 BCMA-35 BCA727- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR C4-H11 ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 350 BCMA-35 BCA727- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYDGWGDYNEKFQGR HLx C4-H11HL specific ATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 351 BCMA-36 BCA715- VHCDR1 aa NHIIH H2-G7 352 BCMA-36 BCA715- VHCDR2 aa YINPYPGYHAYNQKFQG H2-G7 353 BCMA-36 BCA715- VHCDR3 aa DGYYRDTDVLDY H2-G7 354 BCMA-36 BCA715- VLCDR1 aa QASQDISNYLN H2-G7 355 BCMA-36 BCA715- VLCDR2 aa YTSRLHT H2-G7 356 BCMA-36 BCA715- VLCDR3 aa QQGNTLPWT H2-G7 357 BCMA-36 BCA715- VH aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYPGYHAYNQKFQGR H2-G7 VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSS 358 BCMA-36 BCA715- VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGSGS H2-G7 GTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 359 BCMA-36 BCA715- scFv aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYPGYHAYNQKFQGR H2-G7 VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGS GSGTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 360 BCMA-36 BCA715- bi- aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYPGYHAYNQKFQGR HLx H2-G7HL specific VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGS GSGTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 361 BCMA-37 BCA715- VHCDR1 aa NHIIH H2-H11 362 BCMA-37 BCA715- VHCDR2 aa YINPYDGWGDYNQKFQG H2-H11 363 BCMA-37 BCA715- VHCDR3 aa DGYYRDADVLDY H2-H11 364 BCMA-37 BCA715- VLCDR1 aa QASQDISNYLN H2-H11 365 BCMA-37 BCA715- VLCDR2 aa YTSRLHT H2-H11 366 BCMA-37 BCA715- VLCDR3 aa QQGNTLPWT H2-H11 367 BCMA-37 BCA715- VH aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYDGWGDYNQKFQGR H2-H11 VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSS 368 BCMA-37 BCA715- VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGSGS H2-H11 GTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 369 BCMA-37 BCA715- scFv aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYDGWGDYNQKFQGR H2-H11 VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGS GSGTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 370 BCMA-37 BCA715- bi- aa QVQLVQSGAKVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWMGYINPYDGWGDYNQKFQGR HLx H2-H11HL specific VTMTRDKSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGRAPKLLIYYTSRLHTGVPSRFSGS GSGTDYSFTISSLQPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 371 BCMA-38 BCA715- VHCDR1 aa NHIIH H8-G7 372 BCMA-38 BCA715- VHCDR2 aa YINPYPGYHAYNQKFQG H8-G7 373 BCMA-38 BCA715- VHCDR3 aa DGYYRDTDVLDY H8-G7 374 BCMA-38 BCA715- VLCDR1 aa QASQDISNYLN H8-G7 375 BCMA-38 BCA715- VLCDR2 aa YTSRLHT H8-G7 376 BCMA-38 BCA715- VLCDR3 aa QQGNTLPWT H8-G7 377 BCMA-38 BCA715- VH aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYPGYHAYNQKFQGK H8-G7 VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSS 378 BCMA-38 BCA715- VL aa DIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS H8-G7 GTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 379 BCMA-38 BCA715- scFv aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYPGYHAYNQKFQGK H8-G7 VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 380 BCMA-38 BCA715- bi- aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYPGYHAYNQKFQGK HLx H8-G7HL specific VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 381 BCMA-39 BCA715- VHCDR1 aa NHIIH H8-H11 382 BCMA-39 BCA715- VHCDR2 aa YINPYDGWGDYNQKFQG H8-H11 383 BCMA-39 BCA715- VHCDR3 aa DGYYRDADVLDY H8-H11 384 BCMA-39 BCA715- VLCDR1 aa QASQDISNYLN H8-H11 385 BCMA-39 BCA715- VLCDR2 aa YTSRLHT H8-H11 386 BCMA-39 BCA715- VLCDR3 aa QQGNTLPWT H8-H11 387 BCMA-39 BCA715- VH aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYDGWGDYNQKFQGK H8-H11 VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSS 388 BCMA-39 BCA715- VL aa DIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGS H8-H11 GTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 389 BCMA-39 BCA715- scFv aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYDGWGDYNQKFQGK H8-H11 VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIK 390 BCMA-39 BCA715- bi- aa QVQLVQSGAEVIKPGASVKVSCKASGYTFTNHIIHWVRQKPGQGLEWIGYINPYDGWGDYNQKFQGK HLx H8-H11HL specific VTMTRDTSTSTVYMELSSLTSEDTAVYYCARDGYYRDADVLDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGS GSGTDFTFTISSLQQEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 391 BCMA-40 BC7A4 VHCDR1 aa DYYIN 96-D4-A12 392 BCMA-40 BC7A4 VHCDR2 aa WIYFASGNSEYNQKFTG 96-D4-A12 393 BCMA-40 BC7A4 VHCDR3 aa LYDYDWYFDV 96-D4-A12 394 BCMA-40 BC7A4 VLCDR1 aa KSSQSLVHSNGNTYLH 96-D4-A12 395 BCMA-40 BC7A4 VLCDR2 aa KVSNRFS 96-D4-A12 396 BCMA-40 BC7A4 VLCDR3 aa SQSSTAPWT 96-D4-A12 397 BCMA-40 BC7A4 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 96-D4-A12 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 398 BCMA-40 BC7A4 VL aa DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF 96-D4-A12 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 399 BCMA-40 BC7A4 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR 96-D4-A12 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 400 BCMA-40 BC7A4 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx 96-D4-A12 specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL HLx molecule DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF CD3 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG HL SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 401 BCMA-41 BC7A496- VHCDR1 aa DYYIN D4-D7 402 BCMA-41 BC7A496- VHCDR2 aa WIYFASGNSEYNQKFTG D4-D7 403 BCMA-41 BC7A496- VHCDR3 aa LYDYDWYFDV D4-D7 404 BCMA-41 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH D4-D7 405 BCMA-41 BC7A496- VLCDR2 aa KVSNRFS D4-D7 406 BCMA-41 BC7A496- VLCDR3 aa SQSSIYPWT D4-D7 407 BCMA-41 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR D4-D7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 408 BCMA-41 BC7A496- VL aa DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF D4-D7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 409 BCMA-41 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR D4-D7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 410 BCMA-41 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx D4-D7HL specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 411 BCMA-42 BC7A496- VHCDR1 aa DYYIN D4-E7 412 BCMA-42 BC7A496- VHCDR2 aa WIYFASGNSEYNQKFTG D4-E7 413 BCMA-42 BC7A496- VHCDR3 aa LYDYDWYFDV D4-E7 414 BCMA-42 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH D4-E7 415 BCMA-42 BC7A496- VLCDR2 aa KVSNRFS D4-E7 416 BCMA-42 BC7A496- VLCDR3 aa SQSTYPEFT D4-E7 417 BCMA-42 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR D4-E7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 418 BCMA-42 BC7A496- VL aa DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF D4-E7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 419 BCMA-42 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR D4-E7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 420 BCMA-42 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx D4-E7HL specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLPVTLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 421 BCMA-43 BC7A496- VHCDR1 aa DYYIN F4-A12 422 BCMA-43 BC7A496- VHCDR2 aa WIYFASGNSEYNQKFTG F4-A12 423 BCMA-43 BC7A496- VHCDR3 aa LYDYDWYFDV F4-A12 424 BCMA-43 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH F4-A12 425 BCMA-43 BC7A496- VLCDR2 aa KVSNRFS F4-A12 426 BCMA-43 BC7A496- VLCDR3 aa SQSSTAPWT F4-A12 427 BCMA-43 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-A12 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 428 BCMA-43 BC7A496- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF F4-A12 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 429 BCMA-43 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-A12 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 430 BCMA-43 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx F4-A12HL specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 431 BCMA-44 BC7A496- VHCDR1 aa DYYIN F4-D7 432 BCMA-44 BC7A496- VHCDR2 aa WIYFASGNSEYNQKFTG F4-D7 433 BCMA-44 BC7A496- VHCDR3 aa LYDYDWYFDV F4-D7 434 BCMA-44 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH F4-D7 435 BCMA-44 BC7A496- VLCDR2 aa KVSNRFS F4-D7 436 BCMA-44 BC7A496- VLCDR3 aa SQSSIYPWT F4-D7 437 BCMA-44 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-D7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 438 BCMA-44 BC7A496- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF F4-D7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 439 BCMA-44 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-D7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 440 BCMA-44 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx F4-D7HL specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 441 BCMA-45 BC7A496- VHCDR1 aa DYYIN F4-E7 442 BCMA-45 BC7A496- VHCDR2 aa WIYFASGNSEYNQKFTG F4-E7 443 BCMA-45 BC7A496- VHCDR3 aa LYDYDWYFDV F4-E7 444 BCMA-45 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH F4-E7 445 BCMA-45 BC7A496- VLCDR2 aa KVSNRFS F4-E7 446 BCMA-45 BC7A496- VLCDR3 aa SQSTYPEFT F4-E7 447 BCMA-45 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-E7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 448 BCMA-45 BC7A496- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF F4-E7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 449 BCMA-45 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR F4-E7 VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 450 BCMA-45 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx F4-E7HL specific VTMTRDTSISTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 451 BCMA-46 BC7A496- VHCDR1 aa DYYIN G2-A12 452 BCMA-46 BC7A496- VHCDR2 aa WIYFASGNSEYNEKFTG G2-A12 453 BCMA-46 BC7A496- VHCDR3 aa LYDYDWYFDV G2-A12 454 BCMA-46 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH G2-A12 455 BCMA-46 BC7A496- VLCDR2 aa KVSNRFS G2-A12 456 BCMA-46 BC7A496- VLCDR3 aa SQSSTAPWT G2-A12 457 BCMA-46 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-A12 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 458 BCMA-46 BC7A496- VL aa DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF G2-A12 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 459 BCMA-46 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-A12 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIK 460 BCMA-46 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR HLx G2-A12HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSTAPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 461 BCMA-47 BC7A496- VHCDR1 aa DYYIN G2-D7 462 BCMA-47 BC7A496- VHCDR2 aa WIYFASGNSEYNEKFTG G2-D7 463 BCMA-47 BC7A496- VHCDR3 aa LYDYDWYFDV G2-D7 464 BCMA-47 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH G2-D7 465 BCMA-47 BC7A496- VLCDR2 aa KVSNRFS G2-D7 466 BCMA-47 BC7A496- VLCDR3 aa SQSSIYPWT G2-D7 467 BCMA-47 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-D7 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 468 BCMA-47 BC7A496- VL aa DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF G2-D7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 469 BCMA-47 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-D7 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIK 470 BCMA-47 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR HLx G2-D7HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSSIYPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 471 BCMA-48 BC7A496- VHCDR1 aa DYYIN G2-E7 472 BCMA-48 BC7A496- VHCDR2 aa WIYFASGNSEYNEKFTG G2-E7 473 BCMA-48 BC7A496- VHCDR3 aa LYDYDWYFDV G2-E7 474 BCMA-48 BC7A496- VLCDR1 aa KSSQSLVHSNGNTYLH G2-E7 475 BCMA-48 BC7A496- VLCDR2 aa KVSNRFS G2-E7 476 BCMA-48 BC7A496- VLCDR3 aa SQSTYPEFT G2-E7 477 BCMA-48 BC7A496- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-E7 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 478 BCMA-48 BC7A496- VL aa DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF G2-E7 SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 479 BCMA-48 BC7A496- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR G2-E7 VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIK 480 BCMA-48 BC7A496- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNEKFTGR HLx G2-E7HL specific VTMTRDTSSSTAYMELSSLRSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVSLGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGVYYCSQSTYPEFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 481 BCMA-49 BC7A497- VHCDR1 aa DYYIN A3-A12 482 BCMA-49 BC7A497- VHCDR2 aa WIYFASGNSEYNQKFTG A3-A12 483 BCMA-49 BC7A497- VHCDR3 aa LYDYDWYFDV A3-A12 484 BCMA-49 BC7A497- VLCDR1 aa KSSQSLVHSNGNTYLH A3-A12 485 BCMA-49 BC7A497- VLCDR2 aa KVSNRFS A3-A12 486 BCMA-49 BC7A497- VLCDR3 aa SQSSTAPWT A3-A12 487 BCMA-49 BC7A497- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-A12 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 488 BCMA-49 BC7A497- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF A3-A12 SGSGSGTDFTLKISRVEAEDVGIYYCSQSSTAPWTFGQGTKLEIK 489 BCMA-49 BC7A497- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-A12 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSSTAPWTFGQGTKLEIK 490 BCMA-49 BC7A497- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx A3-A12HL specific VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSSTAPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 491 BCMA-50 BC7A497- VHCDR1 aa DYYIN A3-D7 492 BCMA-50 BC7A497- VHCDR2 aa WIYFASGNSEYNQKFTG A3-D7 493 BCMA-50 BC7A497- VHCDR3 aa LYDYDWYFDV A3-D7 494 BCMA-50 BC7A497- VLCDR1 aa KSSQSLVHSNGNTYLH A3-D7 495 BCMA-50 BC7A497- VLCDR2 aa KVSNRFS A3-D7 496 BCMA-50 BC7A497- VLCDR3 aa SQSSIYPWT A3-D7 497 BCMA-50 BC7A497- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-D7 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 498 BCMA-50 BC7A497- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF A3-D7 SGSGSGTDFTLKISRVEAEDVGIYYCSQSSIYPWTFGQGTKLEIK 499 BCMA-50 BC7A497- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-D7 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSSIYPWTFGQGTKLEIK 500 BCMA-50 BC7A497- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx A3-D7HL specific VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSSIYPWTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 501 BCMA-51 BC7A497- VHCDR1 aa DYYIN A3-E7 502 BCMA-51 BC7A497- VHCDR2 aa WIYFASGNSEYNQKFTG A3-E7 503 BCMA-51 BC7A497- VHCDR3 aa LYDYDWYFDV A3-E7 504 BCMA-51 BC7A497- VLCDR1 aa KSSQSLVHSNGNTYLH A3-E7 505 BCMA-51 BC7A497- VLCDR2 aa KVSNRFS A3-E7 506 BCMA-51 BC7A497- VLCDR3 aa SQSTYPEFT A3-E7 507 BCMA-51 BC7A497- VH aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-E7 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSS 508 BCMA-51 BC7A497- VL aa DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF A3-E7 SGSGSGTDFTLKISRVEAEDVGIYYCSQSTYPEFTFGQGTKLEIK 509 BCMA-51 BC7A497- scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR A3-E7 VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSTYPEFTFGQGTKLEIK 510 BCMA-51 BC7A497- bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYSFPDYYINWVRQAPGQGLEWMGWIYFASGNSEYNQKFTGR HLx A3-E7HL specific VTMTRDTSINTAYMELSSLTSEDTAVYFCASLYDYDWYFDVWGQGTMVTVSSGGGGSGGGGSGGGGS CD3HL xCD3HL molecule DIVMTQTPLSLSVTPGQPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKVSNRFSGVPDRF SGSGSGTDFTLKISRVEAEDVGIYYCSQSTYPEFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGG SLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 511 BCMA-52 BCE1119- VHCDR1 aa NAWMD F11-F8 512 BCMA-52 BCE1119- VHCDR2 aa QITAKSNNYATYYAEPVKG F11-F8 513 BCMA-52 BCE1119- VHCDR3 aa DGYH F11-F8 514 BCMA-52 BCE1119- VLCDR1 aa RASEDIRNGLA F11-F8 515 BCMA-52 BCE1119- VLCDR2 aa NANSLHT F11-F8 516 BCMA-52 BCE1119- VLCDR3 aa EDTSKYPYT F11-F8 517 BCMA-52 BCE1119- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK F11-F8 GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSS 518 BCMA-52 BCE1119- VL aa AIQMTQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGS F11-F8 GTEFTLKISSLQPEDEATYYCEDTSKYPYTFGQGTKLEIK 519 BCMA-52 BCE1119- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK F11-F8 GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTEF TLKISSLQPEDEATYYCEDTSKYPYTFGQGTKLEIK 520 BCMA-52 BCE1119- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK HLx F11-F8HL specific GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTEF TLKISSLQPEDEATYYCEDTSKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 521 BCMA-53 BCE1119- VHCDR1 aa NAWMD G3-F8 522 BCMA-53 BCE1119- VHCDR2 aa QITAKSNNYATYYAAPVKG G3-F8 523 BCMA-53 BCE1119- VHCDR3 aa DGYH G3-F8 524 BCMA-53 BCE1119- VLCDR1 aa RASEDIRNGLA G3-F8 525 BCMA-53 BCE1119- VLCDR2 aa NANSLHS G3-F8 526 BCMA-53 BCE1119- VLCDR3 aa EDTSKYPYT G3-F8 527 BCMA-53 BCE1119- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK G3-F8 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSS 528 BCMA-53 BCE1119- VL aa AIQMTQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGS G3-F8 GTDFTLTISSMQPEDEGTYYCEDTSKYPYTFGQGTKLEIK 529 BCMA-53 BCE1119- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK G3-F8 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGSGTDF TLTISSMQPEDEGTYYCEDTSKYPYTFGQGTKLEIK 530 BCMA-53 BCE1119- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK HLx G3-F8HL specific GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGSGTDF TLTISSMQPEDEGTYYCEDTSKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 531 BCMA-54 BCE1119- VHCDR1 aa NAWMD B2-F8 532 BCMA-54 BCE1119- VHCDR2 aa QITAKSNNYATYYAAPVKG B2-F8 533 BCMA-54 BCE1119- VHCDR3 aa DGYH B2-F8 534 BCMA-54 BCE1119- VLCDR1 aa RASEDIRNGLA B2-F8 535 BCMA-54 BCE1119- VLCDR2 aa NANSLHT B2-F8 536 BCMA-54 BCE1119- VLCDR3 aa EDTSKYPYT B2-F8 537 BCMA-54 BCE1119- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK B2-F8 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSS 538 BCMA-54 BCE1119- VL aa AIQMTQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGS B2-F8 GTDFTLTISSLQPEDEAIYYCEDTSKYPYTFGQGTKLEIK 539 BCMA-54 BCE1119- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK B2-F8 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISSLQPEDEAIYYCEDTSKYPYTFGQGTKLEIK 540 BCMA-54 BCE1119- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK HLx B2-F8HL specific GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISSLQPEDEAIYYCEDTSKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 541 BCMA-55 BCE11-20- VHCDR1 aa NAWMD H9-E9 542 BCMA-55 BCE11-20- VHCDR2 aa QITAKSNNYATYYAAPVKG H9-E9 543 BCMA-55 BCE11-20- VHCDR3 aa DGYH H9-E9 544 BCMA-55 BCE11-20- VLCDR1 aa RASEDIRNGLA H9-E9 545 BCMA-55 BCE11-20- VLCDR2 aa NANSLHT H9-E9 546 BCMA-55 BCE11-20- VLCDR3 aa EETLKYPYT H9-E9 547 BCMA-55 BCE11-20- VH aa EVQLVESGGSLVKPGGSLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAAPVK H9-E9 GRFTISRDDSKNTLYLQMNSLKEEDTAVYYCTDDGYHWGQGTLVTVSS 548 BCMA-55 BCE11-20- VL aa AIQMTQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGS H9-E9 GTDFTLTISNLQPEDEATYYCEETLKYPYTFGQGTKLEIK 549 BCMA-55 BCE11-20- scFv aa EVQLVESGGSLVKPGGSLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAAPVK H9-E9 GRFTISRDDSKNTLYLQMNSLKEEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISNLQPEDEATYYCEETLKYPYTFGQGTKLEIK 550 BCMA-55 BCE11-20- bi- aa EVQLVESGGSLVKPGGSLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAAPVK HLx H9-E9HL specific GRFTISRDDSKNTLYLQMNSLKEEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISNLQPEDEATYYCEETLKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 551 BCMA-56 BCE11-19- VHCDR1 aa NAWMD F11-E9 552 BCMA-56 BCE11-19- VHCDR2 aa QITAKSNNYATYYAEPVKG F11-E9 553 BCMA-56 BCE11-19- VHCDR3 aa DGYH F11-E9 554 BCMA-56 BCE11-19- VLCDR1 aa RASEDIRNGLA F11-E9 555 BCMA-56 BCE11-19- VLCDR2 aa NANSLHT F11-E9 556 BCMA-56 BCE11-19- VLCDR3 aa EETLKYPYT F11-E9 557 BCMA-56 BCE11-19- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK F11-E9 GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSS 558 BCMA-56 BCE11-19- VL aa AIQMTQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGS F11-E9 GTEFTLKISSLQPEDEATYYCEETLKYPYTFGQGTKLEIK 559 BCMA-56 BCE11-19- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK F11-E9 GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTEF TLKISSLQPEDEATYYCEETLKYPYTFGQGTKLEIK 560 BCMA-56 BCE11-19- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWVAQITAKSNNYATYYAEPVK HLx F11-E9HL specific GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGETVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTEF TLKISSLQPEDEATYYCEETLKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 561 BCMA-57 BCE11-19- VHCDR1 aa NAWMD B2-E9 562 BCMA-57 BCE11-19- VHCDR2 aa QITAKSNNYATYYAAPVKG B2-E9 563 BCMA-57 BCE11-19- VHCDR3 aa DGYH B2-E9 564 BCMA-57 BCE11-19- VLCDR1 aa RASEDIRNGLA B2-E9 565 BCMA-57 BCE11-19- VLCDR2 aa NANSLHT B2-E9 566 BCMA-57 BCE11-19- VLCDR3 aa EETLKYPYT B2-E9 567 BCMA-57 BCE11-19- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK B2-E9 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSS 568 BCMA-57 BCE11-19- VL aa AIQMTQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGS B2-E9 GTDFTLTISSLQPEDEAIYYCEETLKYPYTFGQGTKLEIK 569 BCMA-57 BCE11-19- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK B2-E9 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISSLQPEDEAIYYCEETLKYPYTFGQGTKLEIK 570 BCMA-57 BCE11-19- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK HLx B2-E9HL specific GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGDRVTIACRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHTGVPSRFSGSGSGTDF TLTISSLQPEDEAIYYCEETLKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 571 BCMA-58 BCE11-19- VHCDR1 aa NAWMD G3-E9 572 BCMA-58 BCE11-19- VHCDR2 aa QITAKSNNYATYYAAPVKG G3-E9 573 BCMA-58 BCE11-19- VHCDR3 aa DGYH G3-E9 574 BCMA-58 BCE11-19- VLCDR1 aa RASEDIRNGLA G3-E9 575 BCMA-58 BCE11-19- VLCDR2 aa NANSLHS G3-E9 576 BCMA-58 BCE11-19- VLCDR3 aa EETLKYPYT G3-E9 577 BCMA-58 BCE11-19- VH aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK G3-E9 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSS 578 BCMA-58 BCE11-19- VL aa AIQMTQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGS G3-E9 GTDFTLTISSMQPEDEGTYYCEETLKYPYTFGQGTKLEIK 579 BCMA-58 BCE11-19- scFv aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK G3-E9 GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM TQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGSGTDF TLTISSMQPEDEGTYYCEETLKYPYTGQGTKLEIK 580 BCMA-58 BCE11-19- bi- aa EVQLVESGGGLVKPGESLRLSCAASGFTFSNAWMDWVRQAPGKRLEWIAQITAKSNNYATYYAAPVK HLx G3-E9HL specific GRFTISRDDSKNTLYLQMNSLKKEDTAVYYCTDDGYHWGQGTLVTVSSGGGGSGGGGSGGGGSAIQM CD3HL xCD3HL molecule TQSPSSLSASVGDRVTIKCRASEDIRNGLAWYQQKPGKAPKLLIYNANSLHSGVPSRFSGSGSGTDF TLTISSMQPEDEGTYYCEETLKYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 581 BCMA-59 BC5G9- VHCDR1 aa NYDMA 91-D2 582 BCMA-59 BC5G9- VHCDR2 aa SIITSGGDNYYRDSVKG 91-D2 583 BCMA-59 BC5G9- VHCDR3 aa HDYYDGSYGFAY 91-D2 584 BCMA-59 BC5G9- VLCDR1 aa KASQSVGINVD 91-D2 585 BCMA-59 BC5G9- VLCDR2 aa GASNRHT 91-D2 586 BCMA-59 BC5G9- VLCDR3 aa LQYGSIPFT 91-D2 587 BCMA-59 BC5G9- VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-D2 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS 588 BCMA-59 BC5G9- VL aa EIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-D2 GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 589 BCMA-59 BC5G9- scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-D2 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 590 BCMA-59 BC529- bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR HLx 91-D2HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSEIVMTQSPASMSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 591 BCMA-60 BC5G9- VHCDR1 aa NYDMA 91-C7 592 BCMA-60 BC5G9- VHCDR2 aa SIITSGGDNYYRDSVKG 91-C7 593 BCMA-60 BC5G9- VHCDR3 aa HDYYDGSYGFAY 91-C7 594 BCMA-60 BC5G9- VLCDR1 aa KASQSVGINVD 91-C7 595 BCMA-60 BC5G9- VLCDR2 aa GASNRHT 91-C7 596 BCMA-60 BC5G9- VLCDR3 aa LQYGSIPFT 91-C7 597 BCMA-60 BC5G9- VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-C7 FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS 598 BCMA-60 BC5G9- VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-C7 GREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 599 BCMA-60 BC5G9- scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-C7 FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 600 BCMA-60 BC5G9- bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR HLx 91-C7HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGREFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 601 BCMA-61 BC5G9- VHCDR1 aa NYDMA 91-E4 602 BCMA-61 BC5G9- VHCDR2 aa SIITSGGDNYYRDSVKG 91-E4 603 BCMA-61 BC5G9- VHCDR3 aa HDYYDGSYGFAY 91-E4 604 BCMA-61 BC5G9- VLCDR1 aa KASQSVGINVD 91-E4 605 BCMA-61 BC5G9- VLCDR2 aa GASNRHT 91-E4 606 BCMA-61 BC5G9- VLCDR3 aa LQYGSIPFT 91-E4 607 BCMA-61 BC5G9- VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-E4 FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS 608 BCMA-61 BC5G9- VL aa EIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 91-E4 GTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 609 BCMA-61 BC5G9- scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 91-E4 FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIK 610 BCMA-61 BC5G9- bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR HLx 91-E4HL specific FTISRDNSKNTLYLQMNSLRSEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSEIVMTQSPATLSVSPGERVTLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQSEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 611 BCMA-62 BC5G9- VHCDR1 aa NYDMA 92-E10 612 BCMA-62 BC5G9- VHCDR2 aa SIITSGGDNYYRDSVKG 92-E10 613 BCMA-62 BC5G9- VHCDR3 aa HDYYDGSYGFAY 92-E10 614 BCMA-62 BC5G9- VLCDR1 aa KASQSVGINVD 92-E10 615 BCMA-62 BC5G9- VLCDR2 aa GASNRHT 92-E10 616 BCMA-62 BC5G9- VLCDR3 aa LQYGSIPFT 92-E10 617 BCMA-62 BC5G9- VH aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 92-E10 FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSS 618 BCMA-62 BC5G9- VL aa EIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGSGS 92-E10 GTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK 619 BCMA-62 BC5G9- scFv aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR 92-E10 FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIK 620 BCMA-62 BC5G9- bi- aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVASIITSGGDNYYRDSVKGR HLx 92-E10HL specific FTVSRDNSKNTLYLQMNSLRAEDTAVYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSEIVMTQSPATLSVSPGERATLSCKASQSVGINVDWYQQKPGQAPRLLIYGASNRHTGIPARFSGS GSGTEFTLTISSLQAEDFAVYYCLQYGSIPFTFGPGTKVDIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 621 BCMA-63 BC3A4-37- VHCDR1 aa NYDMA C8 622 BCMA-63 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C8 623 BCMA-63 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C8 624 BCMA-63 BC3A4-37- VLCDR1 aa RASEDIYNGLA C8 625 BCMA-63 BC3A4-37- VLCDR2 aa GASSLQD C8 626 BCMA-63 BC3A4-37- VLCDR3 aa QQSYKYPLT C8 627 BCMA-63 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 628 BCMA-63 BC3A4-37- VL aa AIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C8 GTDYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIK 629 BCMA-63 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIK 630 BCMA-63 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C8HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 631 BCMA-64 BC3A4-37- VHCDR1 aa NYDMA C9 632 BCMA-64 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C9 633 BCMA-64 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C9 634 BCMA-64 BC3A4-37- VLCDR1 aa RASEDIYNGLA C9 635 BCMA-64 BC3A4-37- VLCDR2 aa GASSLQD C9 636 BCMA-64 BC3A4-37- VLCDR3 aa QQSYKYPLT C9 637 BCMA-64 BC3A4-37- VH aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 638 BCMA-64 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C9 GTDFTLTISSMQPEDEATYYCQQSYKYPLTFGGGTKVEIK 639 BCMA-64 BC3A4-37- scFv aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCQQSYKYPLTFGGGTKVEIK 640 BCMA-64 BC3A4-37- bi- as EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C9HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCQQSYKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 641 BCMA-65 BC3A4-37- VHCDR1 aa NYDMA E11 642 BCMA-65 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG E11 643 BCMA-65 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY E11 644 BCMA-65 BC3A4-37- VLCDR1 aa RASEDIYNGLA E11 645 BCMA-65 BC3A4-37- VLCDR2 aa GASSLQD E11 646 BCMA-65 BC3A4-37- VLCDR3 aa QQSYKYPLT E11 647 BCMA-65 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 648 BCMA-65 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS E11 GTHYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIK 649 BCMA-65 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIK 650 BCMA-65 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx E11HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCQQSYKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 651 BCMA-66 BC3A4-37- VHCDR1 aa NYDMA C8-G1 652 BCMA-66 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C8-G1 653 BCMA-66 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C8-G1 654 BCMA-66 BC3A4-37- VLCDR1 aa RASEDIYNGLA C8-G1 655 BCMA-66 BC3A4-37- VLCDR2 aa GASSLQD C8-G1 656 BCMA-66 BC3A4-37- VLCDR3 aa AGPHKYPLT C8-G1 657 BCMA-66 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8-G1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 658 BCMA-66 BC3A4-37- VL aa AIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C8-G1 GTDYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 659 BCMA-66 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8-G1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 660 BCMA-66 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C8-G1HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 661 BCMA-67 BC3A4-37- VHCDR1 aa NYDMA E11-G1 662 BCMA-67 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG E11-G1 663 BCMA-67 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY E11-G1 664 BCMA-67 BC3A4-37- VLCDR1 aa RASEDIYNGLA E11-G1 665 BCMA-67 BC3A4-37- VLCDR2 aa GASSLQD E11-G1 666 BCMA-67 BC3A4-37- VLCDR3 aa AGPHKYPLT E11-G1 667 BCMA-67 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 668 BCMA-67 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS E11-G1 GTHYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 669 BCMA-67 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 670 BCMA-67 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx E11-G1HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 671 BCMA-68 BC3A4-37- VHCDR1 aa NYDMA C8-G8 672 BCMA-68 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C8-G8 673 BCMA-68 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C8-G8 674 BCMA-68 BC3A4-37- VLCDR1 aa RASEDIYNGLA C8-G8 675 BCMA-68 BC3A4-37- VLCDR2 aa GASSLQD C8-G8 676 BCMA-68 BC3A4-37- VLCDR3 aa QQSRNYQQT C8-G8 677 BCMA-68 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8-G8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 678 BCMA-68 BC3A4-37- VL aa AIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C8-G8 GTDYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 679 BCMA-68 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C8-G8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 680 BCMA-68 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C8-G8HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDTVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 681 BCMA-69 BC3A4-37- VHCDR1 aa NYDMA E11-G8 682 BCMA-69 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG E11-G8 683 BCMA-69 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY E11-G8 684 BCMA-69 BC3A4-37- VLCDR1 aa RASEDIYNGLA E11-G8 685 BCMA-69 BC3A4-37- VLCDR2 aa GASSLQD E11-G8 686 BCMA-69 BC3A4-37- VLCDR3 aa QQSRNYQQT E11-G8 687 BCMA-69 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 688 BCMA-69 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS E11-G8 GTHYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 689 BCMA-69 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR E11-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 690 BCMA-69 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx E11-G8HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTHYTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 691 BCMA-70 BC3A4-37- VHCDR1 aa NYDMA A11-G8 692 BCMA-70 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG A11-G8 693 BCMA-70 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY A11-G8 694 BCMA-70 BC3A4-37- VLCDR1 aa RASEDIYNGLA A11-G8 695 BCMA-70 BC3A4-37- VLCDR2 aa GASSLQD A11-G8 696 BCMA-70 BC3A4-37- VLCDR3 aa QQSRNYQQT A11-G8 697 BCMA-70 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR A11-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 698 BCMA-70 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS A11-G8 GTEFTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 699 BCMA-70 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR A11-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTEFTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIK 700 BCMA-70 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx A11-G8HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTEFTLTISSLQPEDEATYYCQQSRNYQQTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 701 BCMA-71 BC3A4-37- VHCDR1 aa NYDMA A11-G1 702 BCMA-71 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG A11-G1 703 BCMA-71 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY A11-G1 704 BCMA-71 BC3A4-37- VLCDR1 aa RASEDIYNGLA A11-G1 705 BCMA-71 BC3A4-37- VLCDR2 aa GASSLQD A11-G1 706 BCMA-71 BC3A4-37- VLCDR3 aa AGPHKYPLT A11-G1 707 BCMA-71 BC3A4-37- VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR A11-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 708 BCMA-71 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS A11-G1 GTEFTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 709 BCMA-71 BC3A4-37- scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR A11-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTEFTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIK 710 BCMA-71 BC3A4-37- bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx A11-G1HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTEFTLTISSLQPEDEATYYCAGPHKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 711 BCMA-72 BC3A4-37- VHCDR1 aa NYDMA C9-G1 712 BCMA-72 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C9-G1 713 BCMA-72 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C9-G1 714 BCMA-72 BC3A4-37- VLCDR1 aa RASEDIYNGLA C9-G1 715 BCMA-72 BC3A4-37- VLCDR2 aa GASSLQD C9-G1 716 BCMA-72 BC3A4-37- VLCDR3 aa AGPHKYPLT C9-G1 717 BCMA-72 BC3A4-37- VH aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 718 BCMA-72 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C9-G1 GTDFTLTISSMQPEDEATYYCAGPHKYPLTFGGGTKVEIK 719 BCMA-72 BC3A4-37- scFv aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9-G1 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCAGPHKYPLTFGGGTKVEIK 720 BCMA-72 BC3A4-37- bi- aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C9-G1HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCAGPHKYPLTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 721 BCMA-73 BC3A4-37- VHCDR1 aa NYDMA C9-G8 722 BCMA-73 BC3A4-37- VHCDR2 aa SISTRGDITSYRDSVKG C9-G8 723 BCMA-73 BC3A4-37- VHCDR3 aa QDYYTDYMGFAY C9-G8 724 BCMA-73 BC3A4-37- VLCDR1 aa RASEDIYNGLA C9-G8 725 BCMA-73 BC3A4-37- VLCDR2 aa GASSLQD C9-G8 726 BCMA-73 BC3A4-37- VLCDR3 aa QQSRNYQQT C9-G8 727 BCMA-73 BC3A4-37- VH aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSS 728 BCMA-73 BC3A4-37- VL aa AIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGSGS C9-G8 GTDFTLTISSMQPEDEATYYCQQSRNYQQTFGGGTKVEIK 729 BCMA-73 BC3A4-37- scFv aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR C9-G8 FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCQQSRNYQQTFGGGTKVEIK 730 BCMA-73 BC3A4-37- bi- aa EVQLLESGGGLVQPGRSLRLSCAASGFTFSNYDMAWVRQAPGKGLEWVSSISTRGDITSYRDSVKGR HLx C9-G8HL specific FTISRDNSKNTLYLQMNSLRAEDTAVYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSAIQMTQSPSSLSASVGDRVTITCRASEDIYNGLAWYQQKPGKAPKLLIYGASSLQDGVPSRFSGS GSGTDFTLTISSMQPEDEATYYCQQSRNYQQTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 731 BCMA-74 BCC3-33- VHCDR1 aa NFDMA D7-B1 732 BCMA-74 BCC3-33- VHCDR2 aa SITTGGGDTYYADSVKG D7-B1 733 BCMA-74 BCC3-33- VHCDR3 aa HGYYDGYHLFDY D7-B1 734 BCMA-74 BCC3-33- VLCDR1 aa RASQGISNYLN D7-B1 735 BCMA-74 BCC3-33- VLCDR2 aa YTSNLQS D7-B1 736 BCMA-74 BCC3-33- VLCDR3 aa MGQTISSYT D7-B1 737 BCMA-74 BCC3-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR D7-B1 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 738 BCMA-74 BCC3-33- VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS D7-B1 GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 739 BCMA-74 BCC3-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR D7-B1 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 740 BCMA-74 BCC3-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx D7-B1HL specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 741 BCMA-75 BCC3-33- VHCDR1 aa NFDMA F8-B1 742 BCMA-75 BCC3-33- VHCDR2 aa SITTGGGDTYYADSVKG F8-B1 743 BCMA-75 BCC3-33- VHCDR3 aa HGYYDGYHLFDY F8-B1 744 BCMA-75 BCC3-33- VLCDR1 aa RASQGISNYLN F8-B1 745 BCMA-75 BCC3-33- VLCDR2 aa YTSNLQS F8-B1 746 BCMA-75 BCC3-33- VLCDR3 aa MGQTISSYT F8-B1 747 BCMA-75 BCC3-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR F8-B1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 748 BCMA-75 BCC3-33- VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS F8-B1 GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 749 BCMA-75 BCC3-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR F8-B1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 750 BCMA-75 BCC3-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx F8-B1HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 751 BCMA-76 BCC3-33- VHCDR1 aa NFDMA F9-B1 752 BCMA-76 BCC3-33- VHCDR2 aa SITTGGGDTYYADSVKG F9-B1 753 BCMA-76 BCC3-33- VHCDR3 aa HGYYDGYHLFDY F9-B1 754 BCMA-76 BCC3-33- VLCDR1 aa RASQGISNYLN F9-B1 755 BCMA-76 BCC3-33- VLCDR2 aa YTSNLQS F9-B1 756 BCMA-76 BCC3-33- VLCDR3 aa MGQTISSYT F9-B1 757 BCMA-76 BCC3-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR F9-B1 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 758 BCMA-76 BCC3-33- VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS F9-B1 GTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 759 BCMA-76 BCC3-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR F9-B1 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 760 BCMA-76 BCC3-33- bi aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx F9-B1HL specific FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 761 BCMA-77 BCC3-33- VHCDR1 aa NFDMA F10B1 762 BCMA-77 BCC3-33- VHCDR2 aa SITTGGGDTYYADSVKG F10B1 763 BCMA-77 BCC3-33- VHCDR3 aa HGYYDGYHLFDY F10B1 764 BCMA-77 BCC3-33- VLCDR1 aa RASQGISNYLN F10B1 765 BCMA-77 BCC3-33- VLCDR2 aa YTSNLQS F10B1 766 BCMA-77 BCC3-33- VLCDR3 aa MGQTISSYT F10B1 767 BCMA-77 BCC3-33- VH aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR F10B1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 768 BCMA-77 BCC3-33- VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS F10B1 GTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 769 BCMA-77 BCC3-33- scFv aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR F10B1 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIK 770 BCMA-77 BCC3-33- bi- aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR HLx F10B1HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCMGQTISSYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 771 BCMA-78 BCE5-33- VHCDR1 aa NFDMA A11-A10 772 BCMA-78 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG A11-A10 773 BCMA-78 BCE5-33- VHCDR3 aa HGYYDGYHLFDY A11-A10 774 BCMA-78 BCE5-33- VLCDR1 aa RASQGISNHLN A11-A10 775 BCMA-78 BCE5-33- VLCDR2 aa YTSNLQS A11-A10 776 BCMA-78 BCE5-33- VLCDR3 aa QQYFDRPYT A11-A10 777 BCMA-78 BCE5-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR A11-A10 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 778 BCMA-78 BCE5-33- VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGSGS A11-A10 GTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 779 BCMA-78 BCE5-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR A11-A10 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 780 BCMA-78 BCE5-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx A11-A10 specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLxCD3 molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGS HL GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 781 BCMA-79 BCE5-33- VHCDR1 aa NFDMA B11-A10 782 BCMA-79 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG B11-A10 783 BCMA-79 BCE5-33- VHCDR3 aa HGYYDGYHLFDY B11-A10 784 BCMA-79 BCE5-33- VLCDR1 aa RASQGISNHLN B11-A10 785 BCMA-79 BCE5-33- VLCDR2 aa YTSNLQS B11-A10 786 BCMA-79 BCE5-33- VLCDR3 aa QQYFDRPYT B11-A10 787 BCMA-79 BCE5-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR B11-A10 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 788 BCMA-79 BCE5-33- VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS B11-A10 GTDYTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 789 BCMA-79 BCE5-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR B11-A10 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 790 BCMA-79 BCE5-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx B11-A10 specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLxCD3 molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HL GSGTDYTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 791 BCMA-80 BCE5-33- VHCDR1 aa NFDMA G11-A10 792 BCMA-80 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG G11-A10 793 BCMA-80 BCE5-33- VHCDR3 aa HGYYDGYHLFDY G11-A10 794 BCMA-80 BCE5-33- VLCDR1 aa RASQGISNHLN G11-A10 795 BCMA-80 BCE5-33- VLCDR2 aa YTSNLQS G11-A10 796 BCMA-80 BCE5-33- VLCDR3 aa QQYFDRPYT G11-A10 797 BCMA-80 BCE5-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR G11-A10 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 798 BCMA-80 BCE5-33- VL aa DIQMTQSPSSLSASVGDRVTITCRASQGISNHLNWFQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS G11-A10 GTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 799 BCMA-80 BCE5-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR G11-A10 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQGISNHLNWFQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 800 BCMA-80 BCE5-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx G11-A10 specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLxCD3 molecule GSDIQMTQSPSSLSASVGDRVTITCRASQGISNHLNWFQQKPGKAPKPLIYYTSNLQSGVPSRFSGS HL GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 801 BCMA-81 BCE5-33- VHCDR1 aa NFDMA G12-A10 802 BCMA-81 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG G12-A10 803 BCMA-81 BCE5-33- VHCDR3 aa HGYYDGYHLFDY G12-A10 804 BCMA-81 BCE5-33- VLCDR1 aa RASQGISNHLN G12-A10 805 BCMA-81 BCE5-33- VLCDR2 aa YTSNLQS G12-A10 806 BCMA-81 BCE5-33- VLCDR3 aa QQYFDRPYT G12-A10 807 BCMA-81 BCE5-33- VH aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR G12-A10 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 808 BCMA-81 BCE5-33- VL aa DIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGSGS G12-A10 GTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 809 BCMA-81 BCE5-33- scFv aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR G12-A10 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIK 810 BCMA-81 BCE5-33- bi- aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR HLx G12-A10 specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLxCD3 molecule GSDIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS HL GSGTDFTLTISSLQPEDFATYYCQQYFDRPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 811 BCMA-82 BCE5-33- VHCDR1 aa NFDMA A11-B8 812 BCMA-82 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG A11-B8 813 BCMA-82 BCE5-33- VHCDR3 aa HGYYDGYHLFDY A11-B8 814 BCMA-82 BCE5-33- VLCDR1 aa RASQGISNHLN A11-B8 815 BCMA-82 BCE5-33- VLCDR2 aa YTSNLQS A11-B8 816 BCMA-82 BCE5-33- VLCDR3 aa QQYSNLPYT A11-B8 817 BCMA-82 BCE5-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR A11-B8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 818 BCMA-82 BCE5-33- VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGSGS A11-B8 GTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 819 BCMA-82 BCE5-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR A11-B8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 820 BCMA-82 BCE5-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx A11-B8HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWFQQKPGRAPKPLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 821 BCMA-83 BCE5-33- VHCDR1 aa NFDMA B11-B8 822 BCMA-83 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG B11-B8 823 BCMA-83 BCE5-33- VHCDR3 aa HGYYDGYHLFDY B11-B8 824 BCMA-83 BCE5-33- VLCDR1 aa RASQGISNHLN B11-B8 825 BCMA-83 BCE5-33- VLCDR2 aa YTSNLQS B11-B8 826 BCMA-83 BCE5-33- VLCDR3 aa QQYSNLPYT B11-B8 827 BCMA-83 BCE5-33- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR B11-B8 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 828 BCMA-83 BCE5-33- VL aa DIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS B11-B8 GTDYTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 829 BCMA-83 BCE5-33- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR B11-B8 FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 830 BCMA-83 BCE5-33- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx B11-B8HL specific FTISRDNAKNTLYLQMDSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQGISNHLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 831 BCMA-84 BCE5-33- VHCDR1 aa NFDMA G12-B8 832 BCMA-84 BCE5-33- VHCDR2 aa SITTGGGDTYYADSVKG G12-B8 833 BCMA-84 BCE5-33- VHCDR3 aa HGYYDGYHLFDY G12-B8 834 BCMA-84 BCE5-33- VLCDR1 aa RASQGISNHLN G12-B8 835 BCMA-84 BCE5-33- VLCDR2 aa YTSNLQS G12-B8 836 BCMA-84 BCE5-33- VLCDR3 aa QQYSNLPYT G12-B8 837 BCMA-84 BCE5-33- VH aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR G12-B8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 838 BCMA-84 BCE5-33- VL aa DIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGSGS G12-B8 GTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 839 BCMA-84 BCE5-33- scFv aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR G12-B8 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIK 840 BCMA-84 BCE5-33- bi- aa EVQLVESGGGLVQPGRSLRLSCAASGFTFSNFDMAWVRQAPAKGLEWVSSITTGGGDTYYADSVKGR HLx G12-B8HL specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGERVTITCRASQGISNHLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQYSNLPYTFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 841 BCMA-85 BCC6-97- VHCDR1 aa NFGMN G5 842 BCMA-85 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG G5 843 BCMA-85 BCC6-97- VHCDR3 aa GGVYGGYDAMDY G5 844 BCMA-85 BCC6-97- VLCDR1 aa RASQDISNYLN G5 845 BCMA-85 BCC6-97- VLCDR2 aa YTSRLHS G5 846 BCMA-85 BCC6-97- VLCDR3 aa QQGNTLPWT G5 847 BCMA-85 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 848 BCMA-85 BCC6-97- VL aa DIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGSGS G5 GTDYTLTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 849 BCMA-85 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK 850 BCMA-85 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx G5HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 851 BCMA-86 BCC6-98- VHCDR1 aa NFGMN C8 852 BCMA-86 BCC6-98- VHCDR2 aa WINTYTGESIYADDFKG C8 853 BCMA-86 BCC6-98- VHCDR3 aa GGVYGGYDAMDY C8 854 BCMA-86 BCC6-98- VLCDR1 aa RASQDISNYLN C8 855 BCMA-86 BCC6-98- VLCDR2 aa YTSRLHS C8 856 BCMA-86 BCC6-98- VLCDR3 aa QQGNTLPWT C8 857 BCMA-86 BCC6-98- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSS 858 BCMA-86 BCC6-98- VL aa DIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGSGS C8 GTDYSLTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 859 BCMA-86 BCC6-98- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 860 BCMA-86 BCC6-98 bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx C8HL specific FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 861 BCMA-87 BCC6-97- VHCDR1 aa NFGMN A6 862 BCMA-87 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG A6 863 BCMA-87 BCC6-97- VHCDR3 aa GGVYGGYDAMDY A6 864 BCMA-87 BCC6-97- VLCDR1 aa RASQDISNYLN A6 865 BCMA-87 BCC6-97- VLCDR2 aa YTSRLHS A6 866 BCMA-87 BCC6-97- VLCDR3 aa QQGNTLPWT A6 867 BCMA-87 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 868 BCMA-87 BCC6-97- VL aa DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A6 GTDYTLTISSLEQEDIATYFCQQGNTLPWTFGQGTKVEIK 869 BCMA-87 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQQGNTLPWTFGQGTKVEIK 870 BCMA-87 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A6HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 871 BCMA-88 BCC6-98- VHCDR1 aa NFGMN C8-E3 872 BCMA-88 BCC6-98- VHCDR2 aa WINTYTGESIYADDFKG C8-E3 873 BCMA-88 BCC6-98- VHCDR3 aa GGVYGGYDAMDY C8-E3 874 BCMA-88 BCC6-98- VLCDR1 aa RASQDISNYLN C8-E3 875 BCMA-88 BCC6-98- VLCDR2 aa YTSRLHS C8-E3 876 BCMA-88 BCC6-98- VLCDR3 aa QSFATLPWT C8-E3 877 BCMA-88 BCC6-98- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8-E3 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSS 878 BCMA-88 BCC6-98- VL aa DIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGSGS C8-E3 GTDYSLTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIK 879 BCMA-88 BCC6-98- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8-E3 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIK 880 BCMA-88 BCC6-98- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx C8-E3HL specific FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 881 BCMA-89 BCC6-98- VHCDR1 aa NFGMN A1-E3 882 BCMA-89 BCC6-98- VHCDR2 aa WINTYTGESIYADDFKG A1-E3 883 BCMA-89 BCC6-98- VHCDR3 aa GGVYGGYDAMDY A1-E3 884 BCMA-89 BCC6-98- VLCDR1 aa RASQDISNYLN A1-E3 885 BCMA-89 BCC6-98- VLCDR2 aa YTSRLHS A1-E3 886 BCMA-89 BCC6-98- VLCDR3 aa QSFATLPWT A1-E3 887 BCMA-89 BCC6-98- VH aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1-E3 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 888 BCMA-89 BCC6-98- VL aa DIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A1-E3 GTDYTFTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIK 889 BCMA-89 BCC6-98- scFv aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1-E3 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIK 890 BCMA-89 BCC6-98- bi- aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A1-E3HL specific FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYYCQSFATLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 891 BCMA-90 BCC6-97- VHCDR1 aa NFGMN G5-E3 892 BCMA-90 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG G5-E3 893 BCMA-90 BCC6-97- VHCDR3 aa GGVYGGYDAMDY G5-E3 894 BCMA-90 BCC6-97- VLCDR1 aa RASQDISNYLN G5-E3 895 BCMA-90 BCC6-97- VLCDR2 aa YTSRLHS G5-E3 896 BCMA-90 BCC6-97- VLCDR3 aa QSFATLPWT G5-E3 897 BCMA-90 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5-E3 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 898 BCMA-90 BCC6-97- VL aa DIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGSGS G5-E3 GTDYTLTISSLEPEDIATYYCQSFATLPWTFGQGTKVEIK 899 BCMA-90 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5-E3 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQSFATLPWTFGQGTKVEIK 900 BCMA-90 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx G5-E3HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQSFATLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 901 BCMA-91 BCC6-97- VHCDR1 aa NFGMN A6-E3 902 BCMA-91 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG A6-E3 903 BCMA-91 BCC6-97- VHCDR3 aa GGVYGGYDAMDY A6-E3 904 BCMA-91 BCC6-97- VLCDR1 aa RASQDISNYLN A6-E3 905 BCMA-91 BCC6-97- VLCDR2 aa YTSRLHS A6-E3 906 BCMA-91 BCC6-97- VLCDR3 aa QSFATLPWT A6-E3 907 BCMA-91 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6-E3 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 908 BCMA-91 BCC6-97- VL aa DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A6-E3 GTDYTLTISSLEQEDIATYFCQSFATLPWTFGQGTKVEIK 909 BCMA-91 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6-E3 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQSFATLPWTFGQGTKVEIK 910 BCMA-91 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A6-E3HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQSFATLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 911 BCMA-92 BCC6-97- VHCDR1 aa NFGMN G5-G9 912 BCMA-92 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG G5-G9 913 BCMA-92 BCC6-97- VHCDR3 aa GGVYGGYDAMDY G5-G9 914 BCMA-92 BCC6-97- VLCDR1 aa RASQDISNYLN G5-G9 915 BCMA-92 BCC6-97- VLCDR2 aa YTSRLHS G5-G9 916 BCMA-92 BCC6-97- VLCDR3 aa QHFRTLPWT G5-G9 917 BCMA-92 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5-G9 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 918 BCMA-92 BCC6-97- VL aa DIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGSGS G5-G9 GTDYTLTISSLEPEDIATYYCQHFRTLPWTFGQGTKVEIK 919 BCMA-92 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR G5-G9 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQHFRTLPWTFGQGTKVEIK 920 BCMA-92 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx G5-G9HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASLGDRVTITCRASQDISNYLNWYQQKPDKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEPEDIATYYCQHFRTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 921 BCMA-93 BCC6-98- VHCDR1 aa NFGMN C8-G9 922 BCMA-93 BCC6-98- VHCDR2 aa WINTYTGESIYADDFKG C8-G9 923 BCMA-93 BCC6-98- VHCDR3 aa GGVYGGYDAMDY C8-G9 924 BCMA-93 BCC6-98- VLCDR1 aa RASQDISNYLN C8-G9 925 BCMA-93 BCC6-98- VLCDR2 aa YTSRLHS C8-G9 926 BCMA-93 BCC6-98- VLCDR3 aa QHFRTLPWT C8-G9 927 BCMA-93 BCC6-98- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8-G9 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSS 928 BCMA-93 BCC6-98- VL aa DIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGSGS C8-G9 GTDYSLTISNLQPEDIATYYCQHFRTLPWTFGQGTKVEIK 929 BCMA-93 BCC6-98- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR C8-G9 FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQHFRTLPWTFGQGTKVEIK 930 BCMA-93 BCC6-98- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx C8-G9HL specific FVFSSDTSVSTAYLQINSLKAEDTAVYFCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKALKLLIYYTSRLHSGVPSRFSGS GSGTDYSLTISNLQPEDIATYYCQHFRTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 931 BCMA-94 BCC6-97- VHCDR1 aa NFGMN A6-G9 932 BCMA-94 BCC6-97- VHCDR2 aa WINTYTGESIYADDFKG A6-G9 933 BCMA-94 BCC6-97- VHCDR3 aa GGVYGGYDAMDY A6-G9 934 BCMA-94 BCC6-97- VLCDR1 aa RASQDISNYLN A6-G9 935 BCMA-94 BCC6-97- VLCDR2 aa YTSRLHS A6-G9 936 BCMA-94 BCC6-97- VLCDR3 aa QHFRTLPWT A6-G9 937 BCMA-94 BCC6-97- VH aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6-G9 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 938 BCMA-94 BCC6-97- VL aa DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A6-G9 GTDYTLTISSLEQEDIATYFCQHFRTLPWTFGQGTKVEIK 939 BCMA-94 BCC6-97- scFv aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A6-G9 FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQHFRTLPWTFGQGTKVEIK 940 BCMA-94 BCC6-97- bi- aa QVQLVQSGSELKKPGASVKVSCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A6-G9HL specific FVFSLDTSVTTAYLQINSLKDEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTLTISSLEQEDIATYFCQHFRTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 941 BCMA-95 BCC6-98- VHCDR1 aa NFGMN A1-G9 942 BCMA-95 BCC6-98- VHCDR2 aa WINTYTGESIYADDFKG A1-G9 943 BCMA-95 BCC6-98- VHCDR3 aa GGVYGGYDAMDY A1-G9 944 BCMA-95 BCC6-98- VLCDR1 aa RASQDISNYLN A1-G9 945 BCMA-95 BCC6-98- VLCDR2 aa YTSRLHS A1-G9 946 BCMA-95 BCC6-98- VLCDR3 aa QHFRTLPWT A1-G9 947 BCMA-95 BCC6-98- VH aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1-G9 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 948 BCMA-95 BCC6-98- VL aa DIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A1-G9 GTDYTFTISNLQPEDIATYFCQHFRTLPWTFGQGTKVEIK 949 BCMA-95 BCC6-98- scFv aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1-G9 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYFCQHFRTLPWTFGQGTKVEIK 950 BCMA-95 BCC6-98- bi- aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A1-G9HL specific FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYFCQHFRTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 951 BCMA-96 BCC698- VHCDR1 aa NFGMN A1 952 BCMA-96 BCC698- VHCDR2 aa WINTYTGESIYADDFKG A1 953 BCMA-96 BCC698- VHCDR3 aa GGVYGGYDAMDY A1 954 BCMA-96 BCC698- VLCDR1 aa RASQDISNYLN A1 955 BCMA-96 BCC698- VLCDR2 aa YTSRLHS A1 956 BCMA-96 BCC698- VLCDR3 aa QQGNTLPWT A1 957 BCMA-96 BCC698- VH aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSS 958 BCMA-96 BCC698- VL aa DIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGS A1 GTDYTFTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 959 BCMA-96 BCC698- scFv aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR A1 FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIK 960 BCMA-96 BCC698- bi aa QVQLVQSGSELKKPGASVKISCKASGYTFTNFGMNWVRQAPGQGLEWMGWINTYTGESIYADDFKGR HLx A1HL specific FVFSSDTSVSTAYLQINNLKAEDTAVYYCARGGVYGGYDAMDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL xCD3HL molecule GSDIQMTQSPSSLSASVGDRVTISCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLHSGVPSRFSGS GSGTDYTFTISNLQPEDIATYYCQQGNTLPWTFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 961 BCMA-97 BCB12- VHCDR1 aa NFDMA 33-G2-B2 962 BCMA-97 BCB12- VHCDR2 aa SITTGGGDTYYADSVKG 33-G2-B2 963 BCMA-97 BCB12- VHCDR3 aa HGYYDGYHLFDY 33-G2-B2 964 BCMA-97 BCB12- VLCDR1 aa RASQGISNNLN 33-G2-B2 965 BCMA-97 BCB12- VLCDR2 aa YTSNLQS 33-G2-B2 966 BCMA-97 BCB12- VLCDR3 aa QQFTSLPYT 33-G2-B2 967 BCMA-97 BCB12- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-G2-B2 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 968 BCMA-97 BCB12- VL aa DIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGSGS 33-G2-B2 GTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 969 BCMA-97 BCB12- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-G2-B2 FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 970 BCMA-97 BCB12- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx 33-G2-B2 specific FTISRDNAKNTLYLQMNSLRAEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLx molecule GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS CD3HL GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 971 BCMA-98 BCB12- VHCDR1 aa NFDMA 33-A4-B2 972 BCMA-98 BCB12- VHCDR2 aa SITTGGGDTYYADSVKG 33-A4-B2 973 BCMA-98 BCB12- VHCDR3 aa HGYYDGYHLFDY 33-A4-B2 974 BCMA-98 BCB12- VLCDR1 aa RANQGISNNLN 33-A4-B2 975 BCMA-98 BCB12- VLCDR2 aa YTSNLQS 33-A4-B2 976 BCMA-98 BCB12- VLCDR3 aa QQFTSLPYT 33-A4-B2 977 BCMA-98 BCB12- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A4-B2 FTISRDNAKSTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 978 BCMA-98 BCB12- VL aa DIQMTQSPSSLSASVGDRVTITCRANQGISNNLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGSGS 33-A4-B2 GTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 979 BCMA-98 BCB12- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A4-B2 FTISRDNAKSTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSLSASVGDRVTITCRANQGISNNLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 980 BCMA-98 BCB12- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx 33-A4-B2 specific FTISRDNAKSTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL HLx molecule GSDIQMTQSPSSLSASVGDRVTITCRANQGISNNLNWYQQKPGKAPKPLIYYTSNLQSGVPSRFSGS CD3HL GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 981 BCMA-99 BCB12- VHCDR1 aa NFDMA 33-A5-B2 982 BCMA-99 BCB12- VHCDR2 aa SITTGGGDTYYADSVKG 33-A5-B2 983 BCMA-99 BCB12- VHCDR3 aa HGYYDGYHLFDY 33-A5-B2 984 BCMA-99 BCB12- VLCDR1 aa RASQGISNNLN 33-A5-B2 985 BCMA-99 BCB12- VLCDR2 aa YTSNLQS 33-A5-B2 986 BCMA-99 BCB12- VLCDR3 aa QQFTSLPYT 33-A5-B2 987 BCMA-99 BCB12- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A5-B2 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 988 BCMA-99 BCB12- VL aa DIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGSGS 33-A5-B2 GTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 989 BCMA-99 BCB12- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A5-B2 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIK 990 BCMA-99 BCB12- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HLx 33- specific FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG CD3HL A5-B2 molecule GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS HLx GSGTDYTLTISSLQPEDFATYYCQQFTSLPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK CD3 LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN HL NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 991 BCMA-100 BCB12- VHCDR1 aa NFDMA 33-A5-C10 992 BCMA-100 BCB12- VHCDR2 aa SITTGGGDTYYADSVKG 33-A5-C10 993 BCMA-100 BCB12- VHCDR3 aa HGYYDGYHLFDY A5-33-C10 994 BCMA-100 BCB12- VLCDR1 aa RASQGISNNLN 33-A5-C10 995 BCMA-100 BCB12- VLCDR2 aa YTSNLQS 33-A5-C10 996 BCMA-100 BCB12- VLCDR3 aa QQFAHLPYT 33-A5-C10 997 BCMA-100 BCB12- VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A5-C10 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSS 998 BCMA-100 BCB12- VL aa DIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGSGS 33-A5-C10 GTDYTLTISSLQPEDFATYYCQQFAHLPYTFGQGTKLEIK 999 BCMA-100 BCB12- scFv aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR 33-A5-C10 FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQFAHLPYTFGQGTKLEIK 1000 BCMA-100 BCB12- bi- aa EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFDMAWVRQAPGKGLVWVSSITTGGGDTYYADSVKGR HL 33-A5-C10 specific FTISRDNAKNTLYLQMDSLRSEDTAVYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGGG xCD3HL HLx molecule GSDIQMTQSPSSMSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKSLIYYTSNLQSGVPSRFSGS CD3 GSGTDYTLTISSLQPEDFATYYCQQFAHLPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLK HL LSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV QPEDEAEYYCVLWYSNRWVFGGGTKLTVL 1001 human human na atgttgcagatggctgggcagtgctcccaaaatgaatattttgacagtttgttgcatgcttgcatac BCMA cttgtcaacttcgatgttcttctaatactcctcctctaacatgtcagcgttattgtaatgcaagtgt gaccaattcagtgaaaggaacgaatgcgattctctggacctgtttgggactgagcttaataatttct ttggcagttttcgtgctaatgtttttgctaaggaagataaactctgaaccattaaaggacgagttta aaaacacaggatcaggtctcctgggcatggctaacattgacctggaaaagagcaggactggtgatga aattattcttccgagaggcctcgagtacacggtggaagaatgcacctgtgaagactgcatcaagagc aaaccgaaggtcgactctgaccattgctttccactcccagctatggaggaaggcgcaaccattcttg tcaccacgaaaacgaatgactattgcaagagcctgccagctgctttgagtgctacggagatagagaa atcaatttctgctaggtaa 1002 human human aa MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVINSVKGTNAILWICLGLSLIIS BCMA LAVFVLMFLLRKINSEPLKDEFKNTGSGLLGMANIDLEKSRTGDEIILPRGLEYTVEECTCEDCIKS KPKVDSDHCFPLPAMEEGATILVITKINDYCKSLPAALSATEIEKSISAR 1003 mouse murine na atggcgcaacagtgtttccacagtgaatattttgacagtctgctgcatgcttgcaaaccgtgtcact BCMA tgcgatgttccaaccctcctgcaacctgtcagccttactgtgatccaagcgtgaccagttcagtgaa agggacgtacacggtgctctggatcttcttggggctgaccttggtcctctctttggcacttttcaca atctcattcttgctgaggaagatgaaccccgaggccctgaaggacgagcctcaaagcccaggtcagc ttgacggatcggctcagctggacaaggccgacaccgagctgactaggatcagggctggtgacgacag gatctttccccgaagcctggagtatacagtggaagagtgcacctgtgaggactgtgtcaagagcaaa cccaagggggattctgaccatttcttcccgcttccagccatggaggagggggcaaccattcttgtca ccacaaaaacgggtgactacggcaagtcaagtgtgccaactgctttgcaaagtgtcatggggatgga gaagccaactcacactagataa 1004 mouse murine aa MAQQCFHSEYFDSLLHACKPCHLRCSNPPATCQPYCDPSVTSSVKGTYTVLWIFLGLTLVLSLALFT BCMA ISFLLRKMNPEALKDEPQSPGQLDGSAQLDKADTELTRIRAGDDRIFPRSLEYTVEECTCEDCVKSK PKGDSDHFFPLPAMEEGATILVTIKTGDYGKSSVPTALQSVMGMEKPTHIR 1005 macaque rhesus na atgttgcagatggctcggcagtgctcccaaaatgaatattttgacagtttgttgcatgattgcaaac BCMA cttgtcaacttcgatgttctagtactcctcctctaacatgtcagcgttattgcaatgcaagtatgac caattcagtgaaaggaatgaatgcgattctctggacctgtttgggactgagcttgataatttctttg gcagttttcgtgctaacgtttttgctaaggaagatgagctctgaaccattaaaggatgagtttaaaa acacaggatcaggtctcctgggcatggctaacattgacctggaaaagggcaggactggtgatgaaat tgttcttccaagaggcctggagtacacggtggaagaatgcacctgtgaagactgcatcaagaataaa ccaaaggttgattctgaccattgctttccactcccagccatggaggaaggcgcaaccattctcgtca ccacgaaaacgaatgactattgcaatagcctgtcagctgctttgagtgttacggagatagagaaatc aatttctgctaggtaa 1006 macaque rhesus aa MLQMARQCSQNEYFDSLLHDCKPCQLRCSSTPPLTCQRYCNASMINSVKGMNAILWICLGLSLIISL BCMA AVFVLTFLLRKMSSEPLKDEFKNTGSGLLGMANIDLEKGRTGDEIVLPRGLEYTVEECTCEDCIKNK PKVDSDHCFPLPAMEEGATILVITKINDYCNSLSAALSVTEIEKSISAR 1007 huBCMA human aa MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA ECD= posi- tions 1-54of SEQID NO:1002 1008 muBCMA murine aa MAQQCFHSEYFDSLLHACKPCHLRCSNPPATCQPYCDPSVTSSVKGTYT ECD= posi- tions 1-49of SEQID NO:1004 1009 huBCMA chimeric aa MAQQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA ECD/E1 hu/mu murine 1010 huBCMA chimeric aa MLQMAGQCFHSEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA ECD/E2 hu/mu murine 1011 huBCMA chimeric aa MLQMAGQCSQNEYFDSLLHACIPCHLRCSNPPATCQPYCNASVTNSVKGTNA ECD/E3 hu/mu murine 1012 huBCMA chimeric aa MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCDPSVTSSVKGTYT ECD/E4 hu/mu murine 1013 huBCMA chimeric aa MLQMAGQCSQNEYFDSLLHACKPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNA ECD/E5 hu/mu murine 1014 huBCMA chimeric aa MLQMAGQCSQNEYFDSLLHACIPCHLRCSSNTPPLTCQRYCNASVTNSVKGTNA ECD/E6 hu/mu murine 1015 huBCMA chimeric aa MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQPYCNASVTNSVKGTNA ECD/E7 hu/mu murine 1016 huBCMA human aa CQLRCSSNTPPLTCQRYC epitope cluster 3 1017 macBCMA macaque aa CQLRCSSTPPLTCQRYC epitope cluster 3 1018 huBCMA human aa MLQMAGQ epitope cluster 1 1019 huBCMA human aa NASVTNSVKGTNA epitope cluster 4 1020 macBCMA macaque aa MLQMARQ epitope cluster 1 1021 macBCMA macaque aa NASMTNSVKGMNA epitope cluster 4 1022 BCMA-101 BC5G9 VHCDR1 aa GFTFSNYDMA 1023 BCMA-101 BC5G9 VHCDR2 aa SIITSGGDNYYRDSVKG 1024 BCMA-101 BC5G9 VHCDR3 aa HDYYDGSYGFAY 1025 BCMA-101 BC5G9 VLCDR1 aa KASQSVGINVD 1026 BCMA-101 BC5G9 VLCDR2 aa GASNRHT 1027 BCMA-101 BC5G9 VLCDR3 aa LQYGSIPFT 1028 BCMA-101 BC5G9 VH aa EVQLVESGGGLVQPGRSLKLSCAASGFTFSNYDMAWVRQAPTKGLEWVASIITSGGDNYYRDSVKGR FTVSRDNAKSTLYLQMDSLRSEDTATYYCVRHDYYDGSYGFAYWGQGTLVTVSS 1029 BCMA-101 BC5G9 VL aa ETVMTQSPTSMSTSIGERVTLNCKASQSVGINVDWYQQTPGQSPKLLIYGASNRHTGVPDRFTGSGF GRDFTLTISNVEAEDLAVYYCLQYGSIPFTFGSGTKLELK 1030 BCMA-101 BC5G9 scFv aa EVQLVESGGGLVQPGRSLKLSCAASGFTFSNYDMAWVRQAPTKGLEWVASIITSGGDNYYRDSVKGR FTVSRDNAKSTLYLQMDSLRSEDTATYYCVRHDYYDGSYGFAYWGQGTLVTVSSGGGGSGGGGGSGG GGSETVMTQSPTSMSTSIGERVTLNCKASQSVGINVDWYQQTPGQSPKLLIYGASNRHTGVPDRFTG SGFGRDFTLTISNVEAEDLAVYYCLQYGSIPFTFGSGTKLELK 1031 BCMA-102 BC244-A7 VHCDR1 aa GYTFTNHIIH 1032 BCMA-102 BC244-A7 VHCDR2 aa YINPYNDDTEYNEKFKG 1033 BCMA-102 BC244-A7 VHCDR3 aa DGYYRDMDVMDY 1034 BCMA-102 BC244-A7 VLCDR1 aa RASQDISNYLN 1035 BCMA-102 BC244-A7 VLCDR2 aa YTSRLHS 1036 BCMA-102 BC244-A7 VLCDR3 aa QQGNTLPWT 1037 BCMA-102 BC244-A7 VH aa EVQLVEQSGPELVKPGASVKMSCKASGYTFTNHIIHWVKQKPGQGLEWIGYINPYNDDTEYNEKFKG KATLTSDKSSTTAYMELSSLTSEDSAVYYCARDGYYRDMDVMDYWGQGTTVTVSS 1038 BCMA-102 BC244-A7 VL aa ELVMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGS GTDYSLTISNLEQEDIATYFCQQGNTLPWTFGGGTKLEIK 1039 BCMA-102 BC244-A7 scFv aa EVQLVEQSGPELVKPGASVKMSCKASGYTFTNHIIHWVKQKPGQGLEWIGYINPYNDDTEYNEKFKG KATLTSDKSSTTAYMELSSLTSEDSAVYYCARDGYYRDMDVMDYWGQGTIVIVSSGGGGSGGGGSGG GGSELVMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSRFSG SGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFGGGTKLEIK 1040 BCMA-103 BC263-A4 VHCDR1 aa GFTFSNYDMA 1041 BCMA-103 BC263-A4 VHCDR2 aa SISTRGDITSYRDSVKG 1042 BCMA-103 BC263-A4 VHCDR3 aa QDYYTDYMGFAY 1043 BCMA-103 BC263-A4 VLCDR1 aa RASEDIYNGLA 1044 BCMA-103 BC263-A4 VLCDR2 aa GASSLQD 1045 BCMA-103 BC263-A4 VLCDR3 aa QQSYKYPLT 1046 BCMA-103 BC263-A4 VH aa EVQLVEESGGGLLQPGRSLKLSCAASGFTFSNYDMAWVRQAPTKGLEWVASISTRGDITSYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCARQDYYTDYMGFAYWGQGTLVTVSS 1047 BCMA-103 BC263-A4 VL aa ELVMTQSPASLSASLGETVTIECRASEDIYNGLAWYQQKPGKSPQLLIYGASSLQDGVPSRFSGSGS GTQYSLKISGMQPEDEANYFCQQSYKYPLTFGSGTKLELK 1048 BCMA-103 BC263-A4 scFv aa EVQLVEESGGGLLQPGRSLKLSCAASGFTFSNYDMAWVRQAPTKGLEWVASISTRGDITSYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCARQDYYTDYMGFAYWGQGTLVTVSSGGGGSGGGGSGG GELVMTQSPASLSASLGETVTIECRASEDIYNGLAWYQQKPGKSPQLLIYGASSLQDGVPSRFSGSG SGTQYSLKISGMQPEDEANYFCQQSYKYPLTFGSGTKLELKGS 1049 BCMA-104 BC271-C3 VHCDR1 aa GFTFSNFDMA 1050 BCMA-104 BC271-C3 VHCDR2 aa SITTGGGDTYYRDSVKG 1051 BCMA-104 BC271-C3 VHCDR3 aa HGYYDGYHLFDY 1052 BCMA-104 BC271-C3 VLCDR1 aa RASQGISNYL 1053 BCMA-104 BC271-C3 VLCDR2 aa YTSNLQS 1054 BCMA-104 BC271-C3 VLCDR3 aa QQYDISSYT 1055 BCMA-104 BC271-C3 VH aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGASVTVSS 1056 BCMA-104 BC271-C3 VL aa ELVMTQTPSSMPASLGERVTISCRASQGISNYLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSGSGS GTDYSLTINSLEPEDFAVYYCQQYDISSYTFGAGTKLEIK 1057 BCMA-104 BC271-C3 scFv aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGASVTVSSGGGGSGGGGSGG GGSELVMTQTPSSMPASLGERVTISCRASQGISNYLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSG SGSGTDYSLTINSLEPEDFAVYYCQQYDISSYTFGAGTKLEIK 1058 BCMA-105 BC265-E5 VHCDR1 aa GFTFSNFDMA 1059 BCMA-105 BC265-E5 VHCDR2 aa SITTGGGDTYYRDSVKG 1060 BCMA-105 BC265-E5 VHCDR3 aa HGYYDGYHLFDY 1061 BCMA-105 BC265-E5 VLCDR1 aa RASQGISNHLN 1062 BCMA-105 BC265-E5 VLCDR2 aa YTSNLQS 1063 BCMA-105 BC265-E5 VLCDR3 aa QQYDSFPLT 1064 BCMA-105 BC265-E5 VH aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGTLVTVSS 1065 BCMA-105 BC265-E5 VL aa ELVMTQTPSSMPASLGERVTISCRASQGISNHLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSGSGS GTDYSLTISSLEPEDFAMYYCQQYDSFPLTFGSGTKLEIK 1066 BCMA-105 BC265-E5 scFv aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGTLVTVSSGGGGSGGGGSGG GGSELVMTQTPSSMPASLGERVTISCRASQGISNHLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSG SGSGTDYSLTISSLEPEDFAMYYCQQYDSFPLTFGSGTKLEIK 1067 BCMA-106 BC271-B12 VHCDR1 aa GFTFSNFDMA 1068 BCMA-106 BC271-B12 VHCDR2 aa SITTGGGDTYYRDSVKG 1069 BCMA-106 BC271-B12 VHCDR3 aa HGYYDGYHLFDY 1070 BCMA-106 BC271-B12 VLCDR1 aa RASQGISNNLN 1071 BCMA-106 BC271-B12 VLCDR2 aa YTSNLQS 1072 BCMA-106 BC271-B12 VLCDR3 aa QQFDTSPYT 1073 BCMA-106 BC271-B12 VH aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGVMVTVSS 1074 BCMA-106 BC271-B12 VL aa ELVMTQTPSSMPASLGERVTISCRASQGISNNLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSGSGS GTDYSLTISSLEPEDFAMYYCQQFDTSPYTFGAGTKLEIK 1075 BCMA-106 BC271-B12 scFv aa EVQLVEESGGGLVQPGRSLKLSCAASGFTFSNFDMAWVRQAPTRGLEWVASITTGGGDTYYRDSVKG RFTISRDNAKSTLYLQMDSLRSEDTATYYCVRHGYYDGYHLFDYWGQGVMVIVSSGGGGSGGGGSGG GGSELVMTQTPSSMPASLGERVTISCRASQGISNNLNWYQQKPDGTIKPLIYYTSNLQSGVPSRFSG SGSGTDYSLTISSLEPEDFAMYYCQQFDTSPYTFGAGTKLEIK 1076 BCMA-107 BC247-A4 VHCDR1 aa GYSFPDYYIN 1077 BCMA-107 BC247-A4 VHCDR2 aa WIYFASGNSEYNE 1078 BCMA-107 BC247-A4 VHCDR3 aa LYDYDWYFDV 1079 BCMA-107 BC247-A4 VLCDR1 aa RSSQSLVHSNGNTYLH 1080 BCMA-107 BC247-A4 VLCDR2 aa KVSNRFS 1081 BCMA-107 BC247-A4 VLCDR3 aa SQSTHVPYT 1082 BCMA-107 BC247-A4 VH aa EVQLVEQSGPELVKPGASVKISCKVSGYSFPDYYINWVKQRPGQGLEWIGWIYFASGNSEYNERFTG KATLTVDTSSNTAYMQLSSLTSEDTAVYFCASLYDYDWYFDVWGQGTTVTVSS 1083 BCMA-107 BC247-A4 VL aa ELVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRF SGSGSGADFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTKLEIK 1084 BCMA-107 BC247-A4 scFv aa EVQLVEQSGPELVKPGASVKISCKVSGYSFPDYYINWVKQRPGQGLEWIGWIYFASGNSEYNERFTG KATLTVDTSSNTAYMQLSSLTSEDTAVYFCASLYDYDWYFDVWGQGTTVTVSSGGGGSGGGGSGGGG SELVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDR FSGSGSGADFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTKLEIK 1085 BCMA-108 BC246-B6 VHCDR1 aa GYSFPDYYIN 1086 BCMA-108 BC246-B6 VHCDR2 aa WIYFASGNSEYNE 1087 BCMA-108 BC246-B6 VHCDR3 aa LYDYDWYFDV 1088 BCMA-108 BC246-B6 VLCDR1 aa RSSQSLVHSNGNTYLH 1089 BCMA-108 BC246-B6 VLCDR2 aa KVSNRFS 1090 BCMA-108 BC246-B6 VLCDR3 aa FQGSHVPWT 1091 BCMA-108 BC246-B6 VH aa EVQLVEQSGPQLVKPGASVKISCKVSGYSFPDYYINWVKQRPGQGLEWIGWIYFASGNSEYNERFTG KATLTVDTSSNTAYMQLSSLTSEDTAVYFCASLYDYDWYFDVWGQGTTVTVSS 1092 BCMA-108 BC246-B6 VL aa ELVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPGRF SGSGSGTDFTLKINRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK 1093 BCMA-108 BC246-B6 scFv aa EVQLVEQSGPQLVKPGASVKISCKVSGYSFPDYYINWVKQRPGQGLEWIGWIYFASGNSEYNERFTG KATLTVDTSSNTAYMQLSSLTSEDTAVYFCASLYDYDWYFDVWGQGTTVTVSSGGGGSGGGGSGGGG SELVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPGR FSGSGSGTDFTLKINRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK