BISPECIFIC ANTIBODY CONSTRUCTS FOR CDH3 AND CD3

Abstract

The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Claims

1-32. (canceled)

33. A method for treating, ameliorating, or preventing a tumor or cancer, the method comprising administering to a subject in need thereof a bispecific single chain antibody construct comprising: a first binding domain which binds to an epitope cluster of human CDH3 on the surface of a target cell; and a second binding domain which binds to human CD3 on the surface of a T cell, wherein the epitope cluster of human CDH3 is comprised within amino acid positions 291-363 (SEQ ID NO: 36) of human CDH3.

34. The method of claim 33, wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of: a) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 169, a CDR-H2 as depicted in SEQ ID NO: 170, and a CDR-H3 as depicted in SEQ ID NO: 171, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 172, a CDR-L2 as depicted in SEQ ID NO: 173, and a CDR-L3 as depicted in SEQ ID NO: 174; b) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 279, a CDR-H2 as depicted in SEQ ID NO: 280, and a CDR-H3 as depicted in SEQ ID NO: 281, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 282, a CDR-L2 as depicted in SEQ ID NO: 283, and a CDR-L3 as depicted in SEQ ID NO: 284; c) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 289, a CDR-H2 as depicted in SEQ ID NO: 290, and a CDR-H3 as depicted in SEQ ID NO: 291, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 292, a CDR-L2 as depicted in SEQ ID NO: 293, and a CDR-L3 as depicted in SEQ ID NO: 294; d) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 299, a CDR-H2 as depicted in SEQ ID NO: 300, and a CDR-H3 as depicted in SEQ ID NO: 301, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 302, a CDR-L2 as depicted in SEQ ID NO: 303, and a CDR-L3 as depicted in SEQ ID NO: 304; e) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 309, a CDR-H2 as depicted in SEQ ID NO: 310, and a CDR-H3 as depicted in SEQ ID NO: 311, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 312, a CDR-L2 as depicted in SEQ ID NO: 313, and a CDR-L3 as depicted in SEQ ID NO: 314.

35. The method of claim 33, wherein the first binding domain binds to an epitope which is comprised within amino acid positions 291-327 (SEQ ID NO: 34) of human CDH3.

36. The method of claim 33, wherein the first binding domain binds to an epitope which is comprised within amino acid positions 328-363 (SEQ ID NO: 35) of human CDH3.

37. The method of claim 36, wherein the first binding domain also binds to an epitope which is comprised within amino acid positions 404-440 (SEQ ID NO: 390) of human CDH3.

38. The method of claim 33, wherein the macaque CDH3 is Macaca fascicularis CDH3.

39. The method of claim 33, wherein the first binding domain comprises a VH region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 175, SEQ ID NO: 285, SEQ ID NO: 295, SEQ ID NO: 305, and SEQ ID NO: 315.

40. The method of claim 33, wherein the first binding domain comprises a VL region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 176, SEQ ID NO: 286, SEQ ID NO: 296, SEQ ID NO: 306, and SEQ ID NO: 316.

41. The method of claim 33, wherein the first binding domain comprises a VH region and a VL region comprising a pair of amino acid sequences selected from the group consisting of SEQ ID NO: 175 and 176, SEQ ID NO: 285 and 286, SEQ ID NO: 295 and 296, SEQ ID NO: 305 and 306, and SEQ ID NO: 315 and 316.

42. The method of claim 33, wherein the first binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 177, SEQ ID NO: 287, SEQ ID NO: 297, SEQ ID NO: 307, and SEQ ID NO: 317.

43. The method of claim 33, wherein the second binding domain binds to human and Callithrix jacchus, Saguinus oedipus or Saimiri sciureus CD3 epsilon.

44. The method of claim 33, wherein the antibody construct comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 178, SEQ ID NO: 288, SEQ ID NO: 298, SEQ ID NO: 308, and SEQ ID NO: 318.

45. The method of claim 33, wherein the antibody construct comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 379, SEQ ID NO: 380, SEQ ID NO: 381, SEQ ID NO: 382, SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388, SEQ ID NO: 389, and SEQ ID NO: 425.

46. The method of claim 33, wherein the cancer is selected from the group consisting of, lung carcinoma, head and neck carcinoma, a primary or secondary CNS tumor, a primary or secondary brain tumor, primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, adrenocortical cancer, esophagus carcinoma, colon cancer, breast cancer, ovarian cancer, NSCLC (non-small cell lung cancer), SCLC (small cell lung cancer), endometrial cancer, cervical cancer, uterine cancer, transitional cell carcinoma, bone cancer, pancreatic cancer, skin cancer, cutaneous or intraocular melanoma, hepatic cancer, biliary duct cancer, gall bladder cancer, kidney cancer, rectal cancer, cancer of the anal region, stomach cancer, gastrointestinal (gastric, colorectal, and duodenal) cancer, cancer of the small intestine, biliary tract cancer, cancer of the urethra, renal cell carcinoma, carcinoma of the endometrium, thyroid cancer, testicular cancer, cutaneous squamous cell cancer, melanoma, stomach cancer, prostate cancer, bladder cancer, osteosarcoma, mesothelioma, Hodgkin's Disease, non-Hodgkins's lymphoma, chronic or acute leukemia, chronic myeloid leukemia, lymphocytic lymphomas, multiple myeloma, fibrosarcoma, neuroblastoma, retinoblastoma, and soft tissue sarcoma.

47. The method of claim 33, wherein the cancer is a squamous cell carcinoma.

48. The method of claim 33, wherein the first binding domain further binds to an epitope cluster of macaque CDH3 on the surface of a target cell.

Description

THE FIGURES SHOW

[0412] FIG. 1:

[0413] Schematic representation of the five extracellular domains D1-D5 of human CDH3, of murine CDH3 and of one exemplary chimeric CDH3 (here: “D1B murine”). Below are shown again the five domains and further their division into three sub-domains each. The interpretation of an exemplary FACS signal (see “epitope clustering” in Example 2) is shown at the bottom right.

[0414] FIG. 2:

[0415] Sequence alignment of human CDH3 and murine CDH3 and exemplary indication of the different domains: signal peptide, pro-peptide, extracellular domains D1-D5, transmembrane domain and cytoplasmatic domain. Murine sequence exchanges of the five extracellular domains were introduced into the human CDH3 backbone, see Example 1, and the chimeric constructs were then used for epitope clustering (epitope mapping), see Example 2.

[0416] FIG. 3:

[0417] Human and murine CDH3 as well as 20 chimeric human-murine CDH3 constructs (five extracellular domains (ECD) and three sub-domains for each ECD) expressed on the surface of CHO cells as shown by flow cytometry. The expression of human wild-type CDH3, murine wild-type CDH3 and of the chimeric CDH3 constructs on CHO cells was verified with a monoclonal mouse IgG1 anti-human CDH3 antibody which is murine cross-reactive. Bound monoclonal antibody was detected with an anti-mouse IgG Fcγ-PE (1:100, 50 μl; Jackson Immunoresearch #115-116-071). D1*): Hu CDH3 D1 mu-CHO.

[0418] FIGS. 4A-4C:

[0419] Epitope mapping of the CDH3 constructs. Examples of binding molecules specific for different epitope clusters/extracellular sub-domains, as detected by epitope mapping of the chimeric CDH3 constructs, see Example 2. FIG. 4A: D1B binders. FIG. 4B: D2C binders. FIG. 4C: D3A binders.

[0420] FIGS. 5A-5D:

[0421] FACS binding analysis of 5 pg/mL purified bispecific antibody monomer on the indicated cell lines. See also Example 5. Detection of the CDH3×CD3 bispecific antibody binding was carried out with an in-house mouse antibody specific for the CD3 binding part of the bispecific antibody, followed by a goat anti mouse Fcγ-PE. Negative control was buffer only, followed by detection antibodies.

[0422] FIGS. 5A and 5B:

[0423] CDH3×CD3 bispecific binders (FIG. 5A: epitope cluster/extracellular sub-domain D2C; FIG. 5B: epitope cluster/extracellular sub-domain D3A) were analyzed for their binding to human CDH3 transfected CHO cells, human CD3 on the human T cell line HPB-all, cyno CDH3 transfected CHO cells, cyno CD3 on the cyno CD3-expressing T cell line HSC-F, human CDH3 positive cell line A431, and murine CDH3 transfected CHO cells (negative control). Binding was detected in all cases, except for the negative control.

[0424] FIGS. 5C and 5D:

[0425] CDH3×CD3 bispecific binders (FIG. 5C: epitope cluster/extracellular sub-domain D2C; FIG. 5D: epitope cluster/extracellular sub-domain D3A) were analyzed for their binding to human CDH3 paralogues CDH1, CDH2, CDH4 and CDH5. No binding to the paralogues was detected. No binding to dhfr.sup.−/− CHO cells (negative control) was detected.

[0426] FIGS. 6A-6B:

[0427] Cytotoxic activity of stimulated human CD8+ T cells against human CDH3-transfected CHO cells in the presence of CDH3×CD3 bispecific antibodies as measured in an 18-hour .sup.51chromium release assay. Effector cells: stimulated enriched human CD8+ T cells. Target cells: Human CDH3 transfected CHO cells. Effector to target cell (E:T) ratio: 10:1. Antibodies specific for epitope cluster/extracellular sub-domain D2C (FIG. 6A) and D3A (FIG. 6B).

[0428] FIGS. 7A-7B:

[0429] Cytotoxic activity of stimulated human CD8+ T cells against the human CDH3 positive epidermoid carcinoma cell line A431 in the presence of CDH3×CD3 bispecific antibodies and as measured in an 18-hour .sup.51chromium release assay. Effector cells: stimulated enriched human CD8+ T cells. Target cells: human A431 cells. Effector to target cell (E:T) ratio: 10:1. Antibodies specific for epitope cluster/extracellular sub-domain D2C (FIG. 7A) and D3A (FIG. 7B).

[0430] FIGS. 8A-8B:

[0431] Cytotoxic activity of unstimulated human PBMC against human CDH3-transfected CHO cells in the presence of CDH3×CD3 bispecific antibodies as measured in an 48-hour FACS-based cytotoxicity assay. Effector cells: unstimulated human PBMC (CD14−/CD56−). Target cells: human CDH3 transfected CHO cells. Effector to target cell (E:T) ratio: 10:1. Antibodies specific for epitope cluster/extracellular sub-domain D2C (FIG. 8A) and D3A (FIG. 8B).

[0432] FIGS. 9A-9B:

[0433] Cytotoxic activity of unstimulated human PBMC against the human CDH3 positive epidermoid carcinoma cell line A431 in the presence of CDH3×CD3 bispecific antibodies as measured in an 48-hour FACS-based cytotoxicity assay. Effector cells: unstimulated human PBMC (CD14−/CD56−). Target cells: human A431 cells. Effector to target cell (E:T) ratio: 10:1. Antibodies specific for epitope cluster/extracellular sub-domain D2C (FIG. 9A) and D3A (FIG. 9B).

[0434] FIGS. 10A-10C:

[0435] Cytotoxic activity of a macaque T cell line against macaque CDH3-transfected CHO cells in the presence of CDH3×CD3 bispecific antibodies as measured in an 48-hour FACS-based cytotoxicity assay. Effector cells: macaque CD3 positive T cell line LnPx4119. Target cells: macaque CDH3 transfected CHO cells. Effector to target cell (E:T)-ratio: 10:1. Antibodies specific for epitope cluster/extracellular sub-domain D2C (FIG. 10A), D3A (FIG. 10B) and D1B (FIG. 10C).

[0436] FIG. 11:

[0437] Anti-tumor activity of a CDH3×CD3 bispecific antibody of epitope cluster/extracellular sub-domain D2C (CDH3-13) in a human tumor xenograft model (see Example 14). The antibody dose-dependently prevents the formation of A-431 tumors in the presence of human PBMCs. High tumor volume at start of measurement (Day 5) due to large volume of cell mixture injected on Day 1. ** p<0.01; *** p<0.0001.

[0438] FIGS. 12A-12B:

[0439] Anti-tumor activity of a CDH3×CD3 bispecific and half-life extended (HLE) antibody of epitope cluster/extracellular sub-domain D2C (CDH3-13) in a human tumor xenograft model (see Example 15). The HLE antibody dose-dependently prevents the formation of human HCT-116 tumors in the presence of human PBMCs. While FIG. 12A shows the overall result, FIG. 12B differentiates the result obtained for the higher antibody concentration (group 2) into responding animals (7/10) and non-responding animals (3/10).

[0440] FIG. 13:

[0441] T cell activation in the absence of target cells with bispecific antibody constructs in the absence (upper panel) and presence (lower panel) of an albumin fusion at the C-terminus of the construct.

EXAMPLES

[0442] The following examples illustrate the invention. These examples should not be construed as to limit the scope of this invention. The present invention is limited only by the claims.

Example 1

[0443] Generation of CHO Cells Expressing Wild Type and Chimeric CDH3

[0444] For the construction of the chimeric molecules used for epitope mapping, the sequence of the respective five extracellular domains Dom1 to Dom5 (or D1 to D5) and of their sub-domains (A, B and C) of human CDH3 was replaced by the corresponding murine sequence. The following 20 molecules were generated; see also FIGS. 1 and 2: [0445] Hu CDH3/Dom1 mu (aa 108-215) SEQ ID NO: 13 [0446] Hu CDH3/Dom1A mu (aa 108-143) SEQ ID NO: 14 [0447] Hu CDH3/Dom1B mu (aa 144-179) SEQ ID NO: 15 [0448] Hu CDH3/Dom1C mu (aa 180-215) SEQ ID NO: 16 [0449] Hu CDH3/Dom2 mu (aa 216-327) SEQ ID NO: 17 [0450] Hu CDH3/Dom2A mu (aa 216-252) SEQ ID NO: 18 [0451] Hu CDH3/Dom2B mu (aa 253-290) SEQ ID NO: 19 [0452] Hu CDH3/Dom2C mu (aa 291-327) SEQ ID NO: 20 [0453] Hu CDH3/Dom3 mu (aa 328-440) SEQ ID NO: 21 [0454] Hu CDH3/Dom3A mu (aa 328-363) SEQ ID NO: 22 [0455] Hu CDH3/Dom3B mu (aa 364-403) SEQ ID NO: 23 [0456] Hu CDH3/Dom3C mu (aa 404-440) SEQ ID NO: 24 [0457] Hu CDH3/Dom4 mu (aa 441-546) SEQ ID NO: 25 [0458] Hu CDH3/Dom4A mu (aa 441-474) SEQ ID NO: 26 [0459] Hu CDH3/Dom4B mu (aa 475-511) SEQ ID NO: 27 [0460] Hu CDH3/Dom4C mu (aa 512-546) SEQ ID NO: 28 [0461] Hu CDH3/Dom5 mu (aa 547-650) SEQ ID NO: 29 [0462] Hu CDH3/Dom5A mu (aa 547-581) SEQ ID NO: 30 [0463] Hu CDH3/Dom5B mu (aa 582-616) SEQ ID NO: 31 [0464] Hu CDH3/Dom5C mu (aa 617-650) SEQ ID NO: 32

[0465] The above listing shows the positions of the different domains (Dom1-Dom5) as well as of the respective sub-domains A-C within the amino acid sequence of human CDH3 as depicted in SEQ ID NO: 1. For example, sub-domain D1A is located in amino acid positions 108-143 of SEQ ID NO: 1. The same similarly applies for all other domains listed above.

[0466] For expression in CHO cells, the coding sequence of the above described chimeric extracellular domains was followed in frame by the coding sequence of an artificial Ser/Gly-linker followed by a domain derived from the transmembrane/intracellular domain of human EpCAM (amino acids 266-314 of the sequence as published in GenBank accession number NM_002354). All chimeric constructs comprised the N-terminal signal sequence (signal peptide) and the pro-peptide.

[0467] For the generation of CHO cells expressing human, cynomolgus macaque (“cyno”), mouse and human/mouse chimeric CDH3, the respective coding sequences of human CDH3 (SEQ ID NO: 2, see also GeneBank accession number NM_001793), cyno CDH3 (SEQ ID NO: 6), mouse CDH3 (SEQ ID NO: 10, see also GeneBank accession number NM_001037809) and of the 20 human-mouse CDH3 chimeras (see above) were cloned into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). The coding sequence of macaque CDH3 was obtained by standard cloning using a cynomolgus spleen cDNA library (BioChain) and human sequence specific oligonucleotides (5′ GGCCCGCCGTCGCGGCAGC 3′; 5′ CTCCTTCTCCAGGTTTGCTGGC 3′; 5′ AACTGAG ACCCCTTGGAGATGC 3′; 5′ TAGTCGTCCTCCCCGCCACC 3′; 5′ GGAGGGTGGGACAAA CACAGG 3′; 5′ ACGTTGAAGTGACCAACGAGGC 3′) hybridizing in the untranslated region or conserved sequence regions of human CDH3 mRNA transcript (NM_001793). Sequence analysis revealed amino acid sequence similarity of the core extracellular domain compared to rhesus CDH3 GenBank sequences (JU473826, JU473827). All cloning 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 construct, a corresponding plasmid was transfected into DHFR deficient CHO cells for eukaryotic expression, as described by Kaufman R. J. (1990) Methods Enzymol. 185, 537-566.

[0468] The expression of CDH3 (human, murine and the chimeric constructs) on CHO cells was verified in a FACS assay using a monoclonal mouse IgG1 anti-human CDH3 antibody which is murine cross-reactive. Bound monoclonal antibody was detected with an anti-mouse IgG Fcγ-PE. As negative control, cells were incubated with PBS/2% FCS instead of the first antibody. The samples were measured by flow cytometry. The results are shown in FIG. 3. The expression of human and cyno CDH3 on CHO cells (see Example 5) was detected with PE-conjugated R&D 861-P.

Example 2

[0469] Epitope Clustering of Murine scFv-Fragments

[0470] Cells transfected with human or murine CDH3, or with the chimeric human/mouse CDH3 molecules (see Example 1) were stained with crude, undiluted periplasmic extract containing scFv binding to human/macaque CDH3. Bound scFv molecules were detected with the mouse monoclonal anti-FLAG-M2 antibody (1 pg/ml; 50 μl in PBS/2% FCS; Sigma F1804) followed by an anti-mouse IgG Fcγ-PE (1:100, 50 μl; Jackson Immunoresearch #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. The results are shown in FIG. 4.

[0471] Specifically, FIG. 4A shows binders which recognize the extracellular domain D1 of human CDH3, and more precisely, the sub-domain D1B (loss of the FACS signal in the respective chimeric CDH3 constructs). Note that the binder denominated CDH3-6 is the parental binder for CDH3-4. The binder denominated CDH3-10 is the parental binder for CDH3-1, CDH3-2 and CDH3-3. FIG. 4B shows binders which recognize the extracellular domain D2 of human CDH3, and more precisely, the sub-domain D2C. Note that the binder denominated CDH3-21 is the parental binder for CDH3-11, CDH3-12 and CDH3-14. The binder denominated CDH3-23 is the parental binder for CDH3-13. Finally, FIG. 4C shows binders which recognize the extracellular domain D3 of human CDH3, and more precisely, the sub-domain D3A. Note that binder CDH3-32 furthermore binds to the sub-domain D3C. The binder denominated CDH3-32 is the parental binder for CDH3-25, CDH3-26 and CDH3-27. The binder denominated CDH3-33 is the parental binder for CDH3-24. The term “parental binder” means in this context that these binders were developed further in order to generate or to obtain optimized binders.

[0472] The binders CDH3-11, CDH3-12, CDH3-13 and CDH3-14 have as well been subjected to the epitope clustering analysis, and they have been shown to recognize the extracellular domain D2 of human CDH3, and more precisely, the sub-domain D2C (data not shown). The same analysis was furthermore carried out with binders CDH3-24, CDH3-25, CDH3-26 and CDH3-27. These binders recognized the extracellular domain D3 of human CDH3, and more precisely, the sub-domain D3A (data not shown).

Example 3

[0473] Biacore-Based Determination of Antibody Affinity to Human and Cynomolgus CDH3

[0474] Biacore analysis experiments were performed using recombinant CDH3 (human and cyno CDH3, respectively) fusion proteins with human albumin (HALB) to determine CDH3 target binding of the antibodies of the invention.

[0475] In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 600-800 RU of the respective recombinant antigen using acetate buffer pH 4.5 according to the manufacturer's manual. The CDH3×CD3 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 μl/min for 3 min, then HBS-EP running buffer was applied for 8 min to 20 min again at a flow rate of 30 μl/ml. Regeneration of the chip was performed using 10 mM glycine 10 mM NaCl pH 1.5 solution. Data sets were analyzed using BiaEval Software. In general two independent experiments were performed.

[0476] The CDH3×CD3 bispecific antibodies according to the invention showed high affinities to human CDH3 in the 1-digit nanomolar range. Binding to macaque CDH3 was balanced, also showing affinities in similar ranges. The affinity values as well as the calculated affinity gap are shown in Table 2. CDH3-25×F12q-HALB and CDH3-13-xI2C-HLE (Fc) were each measured in a separate assay and were shown to have [0477] a KD (hu) of 31.8±1.9 nM, a KD (cyno) of 40.9±3.89 nM and an affinity gap of 1.29, and [0478] a KD (hu) of 12.95±0.5 nM, a KD (cyno) of 12.35±0.35 nM and an affinity gap of 0.95, respectively.

TABLE-US-00002 TABLE 2 Affinities of CDH3 × CD3 bispecific antibodies to human and macaque CDH3 as determined by Biacore analysis, as well as the calculated interspecies affinity gaps. CDH3 × CD3 KD hu CDH3 KD cyno CDH3 Affinity gap bispecific antibody [nM] [nM] cyno/hu CDH3-11 7.5 6.2 0.83 CDH3-12 8.8 7.5 0.85 CDH3-13 7.4 6.0 0.81 CDH3-14 9.5 8.1 0.85 CDH3-24 6.1 5.2 0.85 CDH3-25 7.9 6.7 0.85 CDH3-26 8.8 7.5 0.85 CDH3-27 8.7 7.6 0.87

Example 4

[0479] Scatchard-Based Analysis of CDH3×CD3 Bispecific Antibody Affinity to Human and Macaque CDH3 on Target Antigen Positive Cells and Determination of the Interspecies Affinity Gap

[0480] The affinities of CDH3×CD3 bispecific antibodies to CHO cells transfected with human or macaque CDH3 were also determined by Scatchard analysis as the most reliable method for measuring potential affinity gaps between human and macaque CDH3. For Scatchard analysis, saturation binding experiments are performed using a monovalent detection system to precisely determine monovalent binding of the CDH3×CD3 bispecific antibodies to the respective cell line.

[0481] 2×104 cells of the respective cell line (recombinantly human CDH3-expressing CHO cell line, recombinantly macaque CDH3-expressing CHO cell line) were incubated each with 50 μl of a triplet dilution series (twelve dilutions at 1:2) of the respective CDH3×CD3 bispecific antibody (until saturation is reached) starting at 10-20 nM followed by 16 h incubation at 4° C. under agitation and one residual washing step. Then, the cells were incubated for another hour with 30 μl of a CD3×ALEXA488 conjugate solution. After one washing step, the cells were resuspended in 150 μl FACS buffer containing 3.5% formaldehyde, incubated for further 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS CantoII machine and FACS Diva software. Data were generated from two independent sets of experiments, each using triplicates. Respective Scatchard analysis was calculated to extrapolate maximal binding (Bmax). The concentrations of CDH3×CD3 bispecific antibodies at half-maximal binding were determined reflecting the respective KDs. Values of triplicate measurements were plotted as hyperbolic curves and as S-shaped curves to demonstrate proper concentration ranges from minimal to optimal binding.

[0482] Values depicted in Table 3 were derived from two independent experiments per CDH3×CD3 bispecific antibody. Cell based Scatchard analysis confirmed that the CDH3×CD3 bispecific antibodies of the invention are nanomolar to subnanomolar in affinity to human CDH3 and present with a small cyno/human interspecies CDH3 affinity gap of around 1. CDH3-25×F12q-HALB and CDH3-13×12C-HLE (Fc) were each measured in a separate assay and were shown to have [0483] a cell-based affinity (hu) of 0.37±0.11 nM, a cell-based affinity (cyno) of 0.35±0.08 nM and an affinity gap of 0.95, and [0484] a cell-based affinity (hu) of 0.32±0.003 nM, a cell-based affinity (cyno) of 0.5±0.09 nM and an affinity gap of 1.56, respectively.

TABLE-US-00003 TABLE 3 Affinities (KD) of CDH3 × CD3 bispecific antibodies as determined in cell based Scatchard analysis with the calculated affinity gap KD macaque CDH3/KD human CDH3. Antibodies were measured in two independent experiments, each using triplicates. Cell based Cell based Affinity gap CDH3 × CD3 affinity hu affinity mac KDmac/KDhu bispecific antibody CDH-3 [nM] CDH-3 [nM] CDH-3 CDH3-11 1.74 ± 0.37 1.98 ± 0.67 1.14 CDH3-12 0.40 ± 0.27 0.52 ± 0.21 1.30 CDH3-13 0.42 ± 0.35 0.41 ± 0.28 0.98 CDH3-14 0.49 ± 0.14 0.41 ± 0.03 0.84 CDH3-24 0.09 ± 0.03 0.15 ± 0.07 1.67 CDH3-25 0.12 ± 0.01 0.11 ± 0.03 0.96 CDH3-26 0.17 ± 0.01 0.16 ± 0.04 0.94 CDH3-27 0.20 ± 0.10 0.23 ± 0.03 1.15

Example 5

[0485] Bispecific Binding and Interspecies Cross-Reactivity

[0486] For confirmation of binding to human CDH3 and CD3 and to cyno CDH3 and CD3, bispecific antibodies were tested by flow cytometry using [0487] CHO cells transfected with human and cyno CDH3, respectively, [0488] the human CDH3 positive epidermoid carcinoma cell line A431, [0489] CD3-expressing human T cell leukemia cell line HPB-all (DSMZ, Braunschweig, ACC483), and [0490] the cynomolgus CD3-expressing T cell line HSC-F.

[0491] Moreover, murine CDH3 transfected CHO cells were used as negative control.

[0492] For flow cytometry 200,000 cells of the respective cell lines were incubated for 30 min on ice with 50 μl of purified bispecific antibody at a concentration of 5 μg/ml. The cells were washed twice in PBS/2% FCS and binding of the constructs was detected with an in-house mouse antibody specific for the CD3 binding part. After washing, bound mouse antibodies were detected with a goat anti mouse Fcγ-PE. Samples were measured by flow cytometry.

[0493] The results are shown in FIGS. 5A and 5B. The CDH3×CD3 bispecific antibodies of the invention stained CHO cells transfected with human CDH3 and with cyno CDH3, and they also stained the human CDH3 positive epidermoid carcinoma cell line A431 (natural expresser) as well as human and cyno T cells expressing CD3. Moreover, there was no staining of the negative control cells (murine CDH3 transfected CHO).

Example 6

[0494] Confirmation of the Absence of Binding to Human and Macaque Paralogues

[0495] Human and macaque CDH3 paralogues (CDH1=E-Cadherin, CDH2=N-Cadherin, CDH4=R-Cadherin, and CDH5=VE-Cadherin) were stably transfected into dhfr.sup.−/− CHO cells. Protein expression was confirmed in FACS analyses with antibodies specific for the respective paralogues. Antibodies were R&D MAB18381 (for CDH1), eBioscience 12-3259-41 (for CDH2), R&D Systems polyclonal AF2217 (for CDH4) and BD Bioscience #555661 (for CDH5).

[0496] The sequences of the paralogues as used in the present Example are identified in the sequence listing (SEQ ID NOs: 41-44). They can also be found in the following GenBank, accession numbers:

[0497] NM_004360 [human CDH1]

[0498] NM_001792 [human CDH2]

[0499] NM_001794 [human CDH4]

[0500] NM_001795 [human CDH5]

[0501] The flow cytometry assay was carried out as described in Example 5. The results are shown in FIGS. 5C and 5D. The analysis confirmed that none of the CDH3×CD3 bispecific antibodies of the invention cross-reacts with any of the tested human CDH3 paralogues.

[0502] Antibodies of the invention were also verified to not cross-react with macaque CDH3 paralogues CDH1, CDH2, CDH4, and CDH5 (data not shown). Macaque paralogue expression on CHO cells was verified with the same antibodies as described above for the human paralogues. The sequences of the macaque paralogues as used in the present Example are identified in the sequence listing (SEQ ID NOs 45-48). They can also be found in the following GenBank, accession numbers:

[0503] XM_002802516 [macaque CDH1]

[0504] JU321883 [macaque CDH2]

[0505] XM_002802511 [macaque CDH5]

[0506] In addition, the macaque CDH4 sequence was obtained from Ensembl Genome Browser (ENSMMUT00000017252) and fused N-terminal in frame with the human CDH4 signal peptide (amino acids 1-19).

Example 7

[0507] Identity to Human Germline

[0508] In order to analyze the identity/similarity of the sequence of the antibodies to the human antibody germline genes, the CDH3 binders of the invention were aligned as follows: Full VL including all CDRs was aligned; full VH including CDRs 1 and 2 but except CDR3 was aligned against human antibody germline genes (Vbase). More details can be found in the specification of this application. The results are shown in Table 4 below:

TABLE-US-00004 TABLE 4 Identity of VH and VL to human germline CDH3 × CD3 Identity of VH and VL bispecific antibody to human germline [%] CDH3-11 92.7 CDH3-12 93.6 CDH3-13 87.8 CDH3-14 94.1 CDH3-24 89.4 CDH3-25 89.8 CDH3-26 89.8 CDH3-27 90.7

Example 8

[0509] Cytotoxic Activity

[0510] The potency of CDH3×CD3 bispecific antibodies of the invention in redirecting effector T cells against CDH3-expressing target cells was analyzed in five in vitro cytotoxicity assays: [0511] The potency of CDH3×CD3 bispecific antibodies in redirecting stimulated human CD8+ effector T cells against human CDH3-transfected CHO cells was measured in an 18 hour 51-chromium release assay. Results see FIG. 6. [0512] The potency of CDH3×CD3 bispecific antibodies in redirecting stimulated human CD8+ effector T cells against the CDH3-positive human carcinoma cell line A431 was measured in an 18 hour 51-chromium release assay. Results see FIG. 7. [0513] The potency of CDH3×CD3 bispecific antibodies in redirecting the T cells in unstimulated human PBMC against human CDH3-transfected CHO cells was measured in a 48 hour FACS-based cytotoxicity assay. Results see FIG. 8. [0514] The potency of CDH3×CD3 bispecific antibodies in redirecting the T cells in unstimulated human PBMC against the CDH3-positive human carcinoma cell line A431 was measured in a 48 hour FACS-based cytotoxicity assay. Results see FIG. 9. [0515] For confirmation that the cross-reactive CDH3×CD3 bispecific antibodies are capable of redirecting macaque T cells against macaque CDH3-transfected CHO cells, a 48 hour FACS-based cytotoxicity assay was performed with a macaque T cell line as effector T cells. Results see FIG. 10.

Example 8.1

[0516] Chromium Release Assay with Stimulated Human T Cells

[0517] Stimulated T cells enriched for CD8.sup.+ T cells were obtained as described in the following. A petri dish (145 mm diameter, Greiner bio-one GmbH, Kremsmünster) was coated with a commercially available anti-CD3 specific antibody (OKT3, Orthoclone) in a final concentration of 1 pg/ml for 1 hour at 37° C. Unbound protein was removed by one washing step with PBS. 3-5×10.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.sup.+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4.sup.+ T cells and CD56+NK cells using Dynal-Beads according to the manufacturer's protocol.

[0518] Cyno CDH3- or human CDH3-transfected CHO target cells were washed twice with PBS and labeled with 11.1 MBq .sup.51Cr in a final volume of 100 μl 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 μl supplemented RPMI with an E:T ratio of 10:1. A starting concentration of 0.01-1 pg/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, Köln, 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.

Example 8.2

[0519] Potency of Redirecting Stimulated Human Effector T Cells Against Human CDH3-Transfected CHO Cells

[0520] The cytotoxic activity of CDH3×CD3 bispecific antibodies according to the invention was analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using CHO cells transfected with human CDH3 as target cells, and stimulated human CD8+ T cells as effector cells. The experiment was carried out as described in Example 8.1.

[0521] The results are shown in FIG. 6 and Table 5. The CDH3×CD3 bispecific antibodies showed potent cytotoxic activity against human CDH3 transfected CHO cells, even down to the 1-digit picomolar range. The claimed antibodies—which are specific for the epitope cluster corresponding to positions 291-363 of human CDH3—present with a favorable epitope-activity relationship supporting potent bispecific antibody mediated cytotoxic activity. CDH3-25×F12q-HALB and CDH3-13 xI2C-HLE (Fc) were each measured in a separate assay and were shown to have an EC50 of 3.6 pM and 8.9 pM, respectively.

TABLE-US-00005 TABLE 5 EC50 values [pg/ml] of CDH3 × CD3 bispecific antibodies analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using CHO cells transfected with human CDH3 as target cells, and stimulated human CD8 T cells as effector cells. CDH3 × CD3 bispecific antibody EC50 [pg/ml] CDH3-11 76 CDH3-12 370 CDH3-13 7.2 CDH3-14 138 CDH3-24 14 CDH3-25 4.9 CDH3-26 21 CDH3-27 61

Example 8.3

[0522] Potency of Redirecting Stimulated Human Effector T Cells Against the CDH3-Positive Human Carcinoma Line A431

[0523] The cytotoxic activity of CDH3×CD3 bispecific antibodies was analyzed in a 51-chromium (.sup.51Cr) release cytotoxicity assay using the CDH3-positive human epidermoid carcinoma cell line A431 as source of target cells, and stimulated human CD8+ T cells as effector cells. The assay was carried out as described in Example 8.1.

[0524] In accordance with the results of the 51-chromium release assays with stimulated enriched human CD8+ T lymphocytes as effector cells and human CDH3-transfected CHO cells as target cells, CDH3×CD3 bispecific antibodies of the present invention are also potent in cytotoxic activity against natural expresser target cells (FIG. 7 and Table 6). CDH3-25×F12q-HALB and CDH3-13 xI2C-HLE (Fc) were each measured in a separate assay and were shown to have an EC50 of 1.2 pM and 16 pM, respectively.

TABLE-US-00006 TABLE 6 EC50 values [pg/ml] of CDH3 × CD3 bispecific antibodies analyzed in an 18-hour 51-chromium (.sup.51Cr) release cytotoxicity assay with the CDH3-positive human carcinoma cell line A431 as source of target cells, and stimulated enriched human CD8 T cells as effector cells. CDH3 × CD3 bispecific antibody EC50 [pg/ml] CDH3-11 47 CDH3-12 362 CDH3-13 62 CDH3-14 385 CDH3-24 5.8 CDH3-25 4.6 CDH3-26 19 CDH3-27 31

Example 8.4

[0525] FACS-Based Cytotoxicity Assay with Unstimulated Human PBMC

[0526] Isolation of Effector Cells

[0527] 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 pM EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100×g. 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).

[0528] Depletion of CD14.sup.+ and CD56.sup.+ Cells

[0529] 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 300×g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 μL/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 μL/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 μL/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.

[0530] Target Cell Labeling

[0531] 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 CDH3- or macaque CDH3-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 μL/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 1.25×105 cells/mL. The vitality of cells was determined using 0.5% (v/v) isotonic EosinG solution (Roth, #45380).

[0532] Flow Cytometry Based Analysis

[0533] This assay was designed to quantify the lysis of cyno or human CDH3-transfected CHO cells in the presence of serial dilutions of CDH3 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 μl of this suspension were transferred to each well of a 96-well plate. 40 μL of serial dilutions of the CDH3×CD3 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 μg/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.

[0534] 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:

[00001]$\mathrm{Cytotoxicity}\left[\%\right]=\frac{n_{\mathrm{dead}\mathrm{target}\mathrm{cells}}}{n_{\mathrm{target}\mathrm{cells}}}\times 100$$n=\mathrm{number}\mathrm{of}\mathrm{events}$

[0535] 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 8.5

[0536] Potency of Redirecting Unstimulated Human PBMC Against Human CDH3-Transfected CHO Cells

[0537] The cytotoxic activity of CDH3×CD3 bispecific antibodies was analyzed in a FACS-based cytotoxicity assay using CHO cells transfected with human CDH3 as target cells, and unstimulated human PBMC as effector cells. The assay was carried out as described in Example 8.4 above.

[0538] The results of the FACS-based cytotoxicity assays with unstimulated human PBMC as effector cells and human CDH3-transfected CHO cells as targets are shown in FIG. 8 and Table 7. CDH3-25×F12q-HALB and CDH3-13 xI2C-HLE (Fc) were each measured in a separate assay and were shown to have an EC50 of 4.6 pM and 5.6 pM, respectively.

TABLE-US-00007 TABLE 7 EC50 values [pg/ml] of CDH3 × CD3 bispecific antibodies as measured in a 48-hour FACS-based cytotoxicity assay with unstimulated human PBMC as effector cells and CHO cells transfected with human CDH3 as target cells. CDH3 × CD3 bispecific antibody EC50 [pg/ml] CDH3-11 462 CDH3-12 1021 CDH3-13 129 CDH3-14 1885 CDH3-24 19 CDH3-25 10 CDH3-26 47 CDH3-27 61

Example 8.6

[0539] Potency of Redirecting Unstimulated Human PBMC Against the CDH3-Positive Human Carcinoma Line A431

[0540] The cytotoxic activity of CDH3×CD3 bispecific antibodies was furthermore analyzed in a FACS-based cytotoxicity assay using the CDH3-positive human epidermoid carcinoma cell line A431 as a source of target cells and unstimulated human PBMC as effector cells. The assay was carried out as described in Example 8.4 above. The results are shown in FIG. 9 and Table 8. CDH3-25×F12q-HALB and CDH3-13 xI2C-HLE (Fc) were each measured in a separate assay and were shown to have an EC50 of 2.3 pM and 32 pM, respectively.

TABLE-US-00008 TABLE 8 EC50 values [pg/ml] of CDH3 × CD3 bispecific antibodies oas measured in a 48-hour FACS-based cytotoxicity assay with unstimulated human PBMC as effector cells and the human A431 cell line as source of target cells. CDH3 × CD3 bispecific antibody EC50 [pg/ml] CDH3-11 389 CDH3-12 3141 CDH3-13 83 CDH3-14 4842 CDH3-24 15 CDH3-25 9.2 CDH3-26 35 CDH3-27 41 Expectedly, EC50 values were generally higher in cytotoxicity assays with unstimulated PBMC as effector cells compared with cytotoxicity assays using stimulated human CD8+ T cells.

Example 8.7

[0541] Potency of Redirecting Macaque T Cells Against Macaque CDH3-Expressing CHO Cells

[0542] Finally, the cytotoxic activity of CDH3×CD3 bispecific antibodies was analyzed in a FACS-based cytotoxicity assay using CHO cells transfected with macaque (cyno) CDH3 as target cells, and a macaque T cell line as source of effector cells. 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 CDH3-transfected CHO cells and flow cytometry based analysis of cytotoxic activity was performed as described above.

[0543] Results are shown in FIG. 10 and Table 9. Macaque T cells from cell line 4119LnPx were induced to efficiently kill macaque CDH3-transfected CHO cells by CDH3×CD3 bispecific antibodies of the invention, i.e., antibodies which bind to an epitope cluster of human CDH3 corresponding to positions 291-363 of human CDH3 and encompassing the neighboring sub-domains D2C (positions 291-327) and D3A (positions 328-363). The antibodies presented potently with 2-digit to very low 4-digit pg/ml EC50-values in this assay, confirming that these antibodies are very active in the macaque system.

[0544] Another group of anti-CDH3 antibodies had been identified during epitope clustering (see Example 2), which bind to extracellular domain D1, and more specifically, to the sub-domain D1B of human CDH3. Unexpectedly, CDH3×CD3 bispecific antibodies of this group—although potent in cytotoxic activity against CHO cells transfected with human CDH3—proved to exhibit a very weak cytotoxic activity against the macaque CDH3-transfected CHO cells (see FIG. 10C and Table 9). Antibodies of this group showed a significantly weaker potency with EC50-values in the very high 4-digit and even in the 5-digit pg/ml range. CDH3-25×F12q-HALB and CDH3-13 xI2C-HLE (Fc) were each measured in a separate assay and were shown to have an EC50 of 1.4 pM and 4.0 pM, respectively.

[0545] The CDH3×CD3 antibodies of the invention which bind to an epitope cluster of CDH3 corresponding to positions 291-363 are hence about 5 to almost 1000 times more potent in the macaque system than the antibodies which bind to the extracellular domain D1, and more specifically, to the CDH3 sub-domain DIB.

TABLE-US-00009 TABLE 9 EC50 values [pg/ml] of CDH3 × CD3 bispecific antibodies which bind to a CDH3 epitope cluster corresponding to positions 291-363 (rows 1-8) and of CDH3 × CD3 bispecific antibodies which bind to the CDH3 epitope cluster/sub-domain DIB (rows 9 to 12) 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 CDH3 as target cells. CDH3 × CD3 bispecific antibody EC50 [pg/ml] 1 CDH3-11 1183 2 CDH3-12 1325 3 CDH3-13 257 4 CDH3-14 1015 5 CDH3-24 32 6 CDH3-25 14 7 CDH3-26 37 8 CDH3-27 98 9 CDH3 1 13055 10 CDH3 2 12862 11 CDH3 3 8390 12 CDH3 4 8795

Example 9

[0546] Monomer to Dimer Conversion after (i) Three Freeze/Thaw Cycles and (ii) 7 Days of Incubation at 250 μg/ml

[0547] Bispecific CDH3×CD3 antibody monomer were subjected to different stress conditions followed by high performance SEC to determine the percentage of initially monomeric antibody, which had been converted into antibody dimer.

[0548] (i) 15 μg of monomeric antibody were adjusted to a concentration of 250 μg/ml with generic formulation 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.

[0549] (ii) 15 μg of monomeric antibody were adjusted to a concentration of 250 μg/ml with generic formulation buffer followed by incubation at 37° C. for 7 days. The dimer content was determined by HP-SEC.

[0550] A high resolution SEC Column TSK Gel G3000 SWXL (Tosoh, Tokyo-Japan) was connected to an Äkta Purifier 10 FPLC (GE Lifesciences) equipped with an A905 Autosampler. Column equilibration and running buffer consisted of 100 mM KH2PO4—200 mM Na2SO4 adjusted to pH 6.6. The antibody solution (15 μg 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 Äkta 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.

[0551] The results are shown in Table 10 below. The CDH3×CD3 bispecific antibodies binding to epitope cluster/extracellular sub-domain D2C presented with dimer percentages of ≤1%, and more precisely with dimer percentages of 0.0% after three freeze/thaw cycles as well as after 7 days of incubation at 37° C., which is considered very good. The dimer conversion rates of CDH3×CD3 bispecific antibodies of the epitope cluster/extracellular sub-domain D3A reached values of ≤2%, and more precisely between 0.2 and 1.8, which is considered good. CDH3-25×F12q-HALB and CDH3-13×12C-HLE (Fc) were each measured in a separate assay and were shown to have a percentage of dimer after three freeze/thaw cycles of 1.1 and 0.84, respectively, and a percentage of dimer after 7 days of incubation of 0.0 (both HLE constructs).

TABLE-US-00010 TABLE 10 Percentage of monomeric versus dimeric CDH3 × CD3 bispecific antibodies as determined by High Performance Size Exclusion Chromatography (HP-SEC). CDH3 × CD3 Percentage of dimer after Percentage of dimer after antibody three freeze/thaw cycles 7 days of incubation CDH3-11 0.00 0.00 CDH3-12 0.00 0.00 CDH3-13 0.00 0.00 CDH3-14 0.00 0.00 CDH3-24 1.01 0.20 CDH3-25 1.31 0.60 CDH3-26 0.82 1.80 CDH3-27 1.69 1.50

Example 10

[0552] Thermostability

[0553] Antibody aggregation temperature was determined as follows: 40 μl of antibody solution at 250 μg/ml were transferred into a single use cuvette and placed in a Wyatt Dynamic Light Scattering device DynaPro Nanostar (Wyatt). The sample was heated from 40° C. to 70° C. at a heating rate of 0.5° C./min with constant acquisition of the measured radius. Increase of radius indicating melting of the protein and aggregation was used by the software package delivered with the DLS device to calculate the aggregation temperature of the antibody.

[0554] All tested CDH3×CD3 bispecific antibodies of the invention showed very favorable thermal stability with aggregation temperatures above 54° C., as shown in Table 11 below. CDH3-25×F12q-HALB was measured in a separate assay and was shown to have a thermostability of 56.3° C.

TABLE-US-00011 TABLE 11 Thermostability of the bispecific antibodies as determined by DLS (dynamic light scattering) CDH3 × CD3 Thermostability bispecific antibody (DLS ° C. aggregation) CDH3-11 59.8 CDH3-12 55.9 CDH3-13 59.6 CDH3-14 59.6 CDH3-24 55.1 CDH3-25 55.4 CDH3-26 54.9 CDH3-27 54.1

Example 11

[0555] Stability after Incubation for 24 Hours in Human Plasma

[0556] Purified bispecific antibodies were incubated at the ratio of 1:5 in a human plasma pool at 37° C. for 24 h-96 h at a final concentration of 2-20 μg/ml. After plasma incubation the antibodies were compared in a 51-chromium release assay with stimulated human T cells and CDH3-transfected CHO cells at a starting concentration of 0.01-0.1 μg/ml and with an effector to target cell (E:T) ratio of 10:1 (assay as described in Example 8.1 Chromium release assay with stimulated human T cells). Non-incubated, freshly thawn bispecific antibodies were includes as controls. The results are shown in Table 12. All tested antibodies had a favorable plasma stability (EC.sub.50 plasma/EC.sub.50 control) of ≤4, the group of antibodies binding to D3A even had a plasma stability of ≤3. CDH3-25×F12q-HALB and CDH3-13×12C-HLE (Fc) were each measured in a separate assay and were shown to have [0557] an EC50 w/plasma of 4.4 pM, an EC50 w/o plasma of 3.6 pM, and a plasma to control ratio of 1.2, and [0558] an EC50 w/plasma of 3.4 pM, an EC50 w/o plasma of 8.9 pM, and a plasma to control ratio of 0.4, respectively.

TABLE-US-00012 TABLE 12 EC50 values of the antibodies with and without plasma incubation and calculated plasma/control value Plasma to Control ratio CDH3 × CD3 EC.sub.50 [pg/mL] (EC.sub.50 plasma/ bispecific antibody w/Plasma w/o Plasma EC.sub.50 control) CDH3-11 47 76 0.6 CDH3-12 296 370 0.8 CDH3-13 25 7.2 3.5 CDH3-14 291 138 2.1 CDH3-24 19 14 1.4 CDH3-25 9.9 4.9 2.0 CDH3-26 24 21 1.1 CDH3-27 129 61 2.1

Example 12

[0559] Turbidity at 2500 μg/ml Antibody Concentration

[0560] 1 ml of purified monomeric antibody solution of 250 μg/ml was concentrated by spin concentration units to 2500 μg/ml. After 16h storage at 5° C. the turbidity of the antibody solution was determined by OD340 nm optical absorption measurement against the generic formulation buffer. The results are shown in Table 13 below. All tested antibodies have a very favourable turbidity of ≤0.05. CDH3-25×F12q-HALB and CDH3-13×12C-HLE (Fc) were each measured in a separate assay and were shown to have a turbidity at 2500 μg/ml of 0.066 and 0.026, respectively.

TABLE-US-00013 TABLE 13 Turbidity of the antibody after concentration to 2.5 mg/ml over night CDH3 × CD3 bispecific antibody Turbidity at 2500 μg/ml CDH3-11 0.035 CDH3-12 0.025 CDH3-13 0.030 CDH3-14 0.025 CDH3-24 0.019 CDH3-25 0.026 CDH3-26 0.028 CDH3-27 0.022

Example 14

[0561] Therapeutic Efficacy of a CDH3×CD3 Bispecific Antibody in a Human Tumor Xenograft Model

[0562] On day 1 of the study, cells of the human epidermoid carcinoma cell line A-431 and freshly isolated human PBMC were subcutaneously co-injected in the right dorsal flank of female NOD/SCID mice (E:T cell ratio 1:2). 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 PBMC on tumor growth in the absence of antibody.

[0563] Mice were treated with 0.5 mg/kg/day (group 3, n=10), 0.05 mg/kg/day (group 4, n=10), or 0.005 mg/kg/day (group 5, n=10) of a CDH3×CD3 bispecific antibody specifically binding to the extracellular CDH3 sub-domain D2C by daily intravenous bolus injection for 10 consecutive days, starting approximately 2 hours after tumor cell injection on day 1.

[0564] 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).

[0565] The results are shown in FIG. 11. Treatment of the mice with the CDH3×CD3 bispecific antibody at a dose level of 0.5 mg/kg/day resulted in a complete inhibition of tumor formation, and none of the animals developed a tumor until the end of the study (day 40).

Example 15

[0566] Anti-Tumor Activity of a CDH3×CD3 Bispecific HLE Antibody in an HCT-116 Tumor Model

[0567] The assay was carried out in female NOD/SCID mice subcutaneously injected with human HCT-116 colon carcinoma cells. Effector cells were in vitro expanded and activated human CD3+ T cells (day 12). Treatment was started when tumors had reached a volume of ˜200 mm.sup.3 (day 17). The control group was a q5d vehicle-treated group with T cells. The antibody having SEQ ID NO: 425 was administered at concentrations of 5 mg/kg/admin (group 2) and 0.5 mg/kg/admin (group 3) every five days (q5d) via intravenous bolus injections. The results are shown in FIGS. 12A and 12B. In particular, FIG. 12B differentiates the result in terms of responding animals (7/10) and non-responding animals (3/10). While the reason for non-response in 30% of the animals is not clear, FIG. 12B shows that administration of the half-life extended bispecific construct at a concentration of 5 mg/kg to responding animals leads to a discontinuation of tumor growth starting from the moment of the antibody administration.

Example 16

[0568] T Cell Activation Assay

[0569] Isolated PBMC from healthy human donors were cultured with increasing concentrations of CDH3-13×I2C or CDH3-13×I2C-HALB bispecific antibody constructs for 48 h (serial dilutions of 0.001 pM-20 pM). The expression of the activation marker CD69 on CD4+ and CD8+ T cells was determined by immunostaining and flow cytometry and antigen specific conjugates mAb. The results are shown in FIG. 13 and discussed herein above.

Example 17

[0570] Cyno Pharmacokinetic Study of Half-Life Extended CDH3×CD3 Constructs

[0571] Female cynomolgus monkeys received an i.v. infusion for 60 minutes with 0.015 mg/kg of a half-life extended CDH3×CD3 bispecific antibody construct (admin. volume 1 ml/kg) in buffer. The three HLE formats tested were P156, HALB, and HALB variant 1 (see SEQ ID NOs: 437, 443, and 444), each one fused to the C terminus of the respective construct. The half-life of these HLE constructs in the cyno model was calculated on basis of their blood plasma concentration analyzed at four (P156) and six (HALB, HALB variant 1) time points between 96 hours post-administration and termination of the study. As a result, HLE constructs with P156 showed a half-life of 57 hours, HLE constructs with HALB 63-85 hours and those with HALB variant 1 68 hours, respectively. These PK properties suggest a once weekly i.v. dosing in humans.

TABLE-US-00014 BAYER II SEQUENCES SEQ ID Designa- Format/ NO Epitope tion Source Type Sequence   1 Human human aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM CDH3 GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGFILPVLGAVLALLFLLLVLLLLVRKKRKIKEPLL LPEDDTRDNVFYYGEEGGGEEDQDYDITQLHRGLEARPEVVLRNDVAPTIIPTPMYR PRPANPDEIGNFIIENLKAANTDPTAPPYDTLLVFDYEGSGSDAASLSSLTSSASDQDQ DYDYLNEWGSRFKKLADMYGGGEDD   2 Human human na ATGGGGCTCCCTCGTGGACCTCTCGCGTCTCTCCTCCTTCTCCAGGTTTGCTGGCT CDH3 GCAGTGCGCGGCCTCCGAGCCGTGCCGGGCGGTCTTCAGGGAGGCTGAAGTGAC CTTGGAGGCGGGAGGCGCGGAGCAGGAGCCCGGCCAGGCGCTGGGGAAAGTATT CATGGGCTGCCCTGGGCAAGAGCCAGCTCTGTTTAGCACTGATAATGATGACTTC ACTGTGCGGAATGGCGAGACAGTCCAGGAAAGAAGGTCACTGAAGGAAAGGAA TCCATTGAAGATCTTCCCATCCAAACGTATCTTACGAAGACACAAGAGAGATTGG GTGGTTGCTCCAATATCTGTCCCTGAAAATGGCAAGGGTCCCTTCCCCCAGAGAC TGAATCAGCTCAAGTCTAATAAAGATAGAGACACCAAGATTTTCTACAGCATCAC GGGGCCGGGGGCAGACAGCCCCCCTGAGGGTGTCTTCGCTGTAGAGAAGGAGAC AGGCTGGTTGTTGTTGAATAAGCCACTGGACCGGGAGGAGATTGCCAAGTATGA GCTCTTTGGCCACGCTGTGTCAGAGAATGGTGCCTCAGTGGAGGACCCCATGAAC ATCTCCATCATCGTGACCGACCAGAATGACCACAAGCCCAAGTTTACCCAGGACA CCTTCCGAGGGAGTGTCTTAGAGGGAGTCCTACCAGGTACTTCTGTGATGCAGGT GACAGCCACGGATGAGGATGATGCCATCTACACCTACAATGGGGTGGTTGCTTAC TCCATCCATAGCCAAGAACCAAAGGACCCACACGACCTCATGTTCACCATTCACC GGAGCACAGGCACCATCAGCGTCATCTCCAGTGGCCTGGACCGGGAAAAAGTCC CTGAGTACACACTGACCATCCAGGCCACAGACATGGATGGGGACGGCTCCACCA CCACGGCAGTGGCAGTAGTGGAGATCCTTGATGCCAATGACAATGCTCCCATGTT TGACCCCCAGAAGTACGAGGCCCATGTGCCTGAGAATGCAGTGGGCCATGAGGT GCAGAGGCTGACGGTCACTGATCTGGACGCCCCCAACTCACCAGCGTGGCGTGCC ACCTACCTTATCATGGGCGGTGACGACGGGGACCATTTTACCATCACCACCCACC CTGAGAGCAACCAGGGCATCCTGACAACCAGGAAGGGTTTGGATTTTGAGGCCA AAAACCAGCACACCCTGTACGTTGAAGTGACCAACGAGGCCCCTTTTGTGCTGAA GCTCCCAACCTCCACAGCCACCATAGTGGTCCACGTGGAGGATGTGAATGAGGC ACCTGTGTTTGTCCCACCCTCCAAAGTCGTTGAGGTCCAGGAGGGCATCCCCACT GGGGAGCCTGTGTGTGTCTACACTGCAGAAGACCCTGACAAGGAGAATCAAAAG ATCAGCTACCGCATCCTGAGAGACCCAGCAGGGTGGCTAGCCATGGACCCAGAC AGTGGGCAGGTCACAGCTGTGGGCACCCTCGACCGTGAGGATGAGCAGTTTGTG AGGAACAACATCTATGAAGTCATGGTCTTGGCCATGGACAATGGAAGCCCTCCCA CCACTGGCACGGGAACCCTTCTGCTAACACTGATTGATGTCAATGACCATGGCCC AGTCCCTGAGCCCCGTCAGATCACCATCTGCAACCAAAGCCCTGTGCGCCAGGTG CTGAACATCACGGACAAGGACCTGTCTCCCCACACCTCCCCTTTCCAGGCCCAGC TCACAGATGACTCAGACATCTACTGGACGGCAGAGGTCAACGAGGAAGGTGACA CAGTGGTCTTGTCCCTGAAGAAGTTCCTGAAGCAGGATACATATGACGTGCACCT TTCTCTGTCTGACCATGGCAACAAAGAGCAGCTGACGGTGATCAGGGCCACTGTG TGCGACTGCCATGGCCATGTCGAAACCTGCCCTGGACCCTGGAAGGGAGGTTTCA TCCTCCCTGTGCTGGGGGCTGTCCTGGCTCTGCTGTTCCTCCTGCTGGTGCTGCTT TTGTTGGTGAGAAAGAAGCGGAAGATCAAGGAGCCCCTCCTACTCCCAGAAGAT GACACCCGTGACAACGTCTTCTACTATGGCGAAGAGGGGGGTGGCGAAGAGGAC CAGGACTATGACATCACCCAGCTCCACCGAGGTCTGGAGGCCAGGCCGGAGGTG GTTCTCCGCAATGACGTGGCACCAACCATCATCCCGACACCCATGTACCGTCCTC GGCCAGCCAACCCAGATGAAATCGGCAACTTTATAATTGAGAACCTGAAGGCGG CTAACACAGACCCCACAGCCCCGCCCTACGACACCCTCTTGGTGTTCGACTATGA GGGCAGCGGCTCCGACGCCGCGTCCCTGAGCTCCCTCACCTCCTCCGCCTCCGAC CAAGACCAAGATTACGATTATCTGAACGAGTGGGGCAGCCGCTTCAAGAAGCTG GCAGACATGTACGGTGGCGGGGAGGACGAC   3 Human human aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM CDH3 GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI ECD SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGG   4 Human human na ATGGGGCTCCCTCGTGGACCTCTCGCGTCTCTCCTCCTTCTCCAGGTTTGCTGGCT CDH3 GCAGTGCGCGGCCTCCGAGCCGTGCCGGGCGGTCTTCAGGGAGGCTGAAGTGAC ECD CTTGGAGGCGGGAGGCGCGGAGCAGGAGCCCGGCCAGGCGCTGGGGAAAGTATT CATGGGCTGCCCTGGGCAAGAGCCAGCTCTGTTTAGCACTGATAATGATGACTTC ACTGTGCGGAATGGCGAGACAGTCCAGGAAAGAAGGTCACTGAAGGAAAGGAA TCCATTGAAGATCTTCCCATCCAAACGTATCTTACGAAGACACAAGAGAGATTGG GTGGTTGCTCCAATATCTGTCCCTGAAAATGGCAAGGGTCCCTTCCCCCAGAGAC TGAATCAGCTCAAGTCTAATAAAGATAGAGACACCAAGATTTTCTACAGCATCAC GGGGCCGGGGGCAGACAGCCCCCCTGAGGGTGTCTTCGCTGTAGAGAAGGAGAC AGGCTGGTTGTTGTTGAATAAGCCACTGGACCGGGAGGAGATTGCCAAGTATGA GCTCTTTGGCCACGCTGTGTCAGAGAATGGTGCCTCAGTGGAGGACCCCATGAAC ATCTCCATCATCGTGACCGACCAGAATGACCACAAGCCCAAGTTTACCCAGGACA CCTTCCGAGGGAGTGTCTTAGAGGGAGTCCTACCAGGTACTTCTGTGATGCAGGT GACAGCCACGGATGAGGATGATGCCATCTACACCTACAATGGGGTGGTTGCTTAC TCCATCCATAGCCAAGAACCAAAGGACCCACACGACCTCATGTTCACCATTCACC GGAGCACAGGCACCATCAGCGTCATCTCCAGTGGCCTGGACCGGGAAAAAGTCC CTGAGTACACACTGACCATCCAGGCCACAGACATGGATGGGGACGGCTCCACCA CCACGGCAGTGGCAGTAGTGGAGATCCTTGATGCCAATGACAATGCTCCCATGTT TGACCCCCAGAAGTACGAGGCCCATGTGCCTGAGAATGCAGTGGGCCATGAGGT GCAGAGGCTGACGGTCACTGATCTGGACGCCCCCAACTCACCAGCGTGGCGTGCC ACCTACCTTATCATGGGCGGTGACGACGGGGACCATTTTACCATCACCACCCACC CTGAGAGCAACCAGGGCATCCTGACAACCAGGAAGGGTTTGGATTTTGAGGCCA AAAACCAGCACACCCTGTACGTTGAAGTGACCAACGAGGCCCCTTTTGTGCTGAA GCTCCCAACCTCCACAGCCACCATAGTGGTCCACGTGGAGGATGTGAATGAGGC ACCTGTGTTTGTCCCACCCTCCAAAGTCGTTGAGGTCCAGGAGGGCATCCCCACT GGGGAGCCTGTGTGTGTCTACACTGCAGAAGACCCTGACAAGGAGAATCAAAAG ATCAGCTACCGCATCCTGAGAGACCCAGCAGGGTGGCTAGCCATGGACCCAGAC AGTGGGCAGGTCACAGCTGTGGGCACCCTCGACCGTGAGGATGAGCAGTTTGTG AGGAACAACATCTATGAAGTCATGGTCTTGGCCATGGACAATGGAAGCCCTCCCA CCACTGGCACGGGAACCCTTCTGCTAACACTGATTGATGTCAATGACCATGGCCC AGTCCCTGAGCCCCGTCAGATCACCATCTGCAACCAAAGCCCTGTGCGCCAGGTG CTGAACATCACGGACAAGGACCTGTCTCCCCACACCTCCCCTTTCCAGGCCCAGC TCACAGATGACTCAGACATCTACTGGACGGCAGAGGTCAACGAGGAAGGTGACA CAGTGGTCTTGTCCCTGAAGAAGTTCCTGAAGCAGGATACATATGACGTGCACCT TTCTCTGTCTGACCATGGCAACAAAGAGCAGCTGACGGTGATCAGGGCCACTGTG TGCGACTGCCATGGCCATGTCGAAACCTGCCCTGGACCCTGGAAGGGAGGT   5 Macaque cynomol aa MGLPRGPLACLLLVQVCWLQCAASEPCRAIFGEAEVTLEAGGAEQEPSQALGKVFM CDH3 gus GCPGQKPALFSTVNDDFTVQNGETVQDRKSLKERNPLKIFPSKRILRRHKRDWVVAPI SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIHTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPVFDPQKYESHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIVGGDDGDHFTIATHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEAV CVYTAKDPDKENQKISYRILRDPAGWLAMDPDSGQVTVAGTLDREDERFVRNNIYE VMVLAVDNGSPPTTGTGTLLLTLIDVNDHGPVPEPREITICNQSPESQVLNITDKDLSP HTSPFQAQLTDDSDIYWMAEVNEKDDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVEKCPDPWKGGFILPVLGAVLALLLLLLVLLLLVRKKRKVKEPL LLPEDDTRDNVFYYGEEGGGEEDQDYDITQLHRGLEARPEVVLRNDVAPTFIPTPMY RPRPANPDEIGNFIIENLKAANTDPTAPPYDSLLVFDYEGSGSDAASLSSLTTSTSDQD QDYDYLNEWGSRFKKLADMYGGGDDD   6 Macaque cynomol na ATGGGGCTCCCTCGTGGACCTCTCGCGTGTCTCCTCCTCGTCCAGGTTTGCTGGCT CDH3 gus GCAATGCGCGGCCTCCGAGCCGTGCCGGGCGATCTTCGGGGAGGCTGAAGTGAC CTTGGAGGCGGGAGGCGCGGAGCAGGAGCCCAGCCAGGCCCTGGGGAAAGTATT CATGGGCTGCCCTGGGCAAAAGCCAGCTCTGTTTAGCACTGTTAATGACGACTTC ACTGTGCAGAATGGCGAGACAGTCCAGGACAGAAAGTCACTGAAAGAAAGGAAT CCATTGAAGATCTTCCCATCCAAACGTATCTTACGAAGACACAAGAGAGATTGGG TGGTTGCTCCAATATCTGTCCCTGAAAATGGCAAGGGTCCCTTCCCGCAGAGGCT GAATCAGCTCAAGTCTAATAAAGACAGAGACACGAAGATTTTCTACAGCATCAC GGGGCCGGGGGCAGACAGCCCCCCTGAGGGCGTCTTTGCTGTAGAGAAAGAGAC AGGCTGGTTGTTGTTGAACAAGCCACTGGACCGGGAGGAGATTGCCAAGTATGA GCTCTTTGGCCACGCTGTGTCAGAGAATGGTGCCTCAGTGGAGGATCCCATGAAC ATCTCCATCATCGTGACCGACCAGAATGACCACAAGCCCAAGTTTACCCAGGACA CCTTCCGAGGGAGTGTCTTAGAGGGAGTCCTACCAGGTACTTCTGTGATGCAGGT GACGGCCACAGATGAGGATGATGCCATCCACACCTACAATGGGGTGGTTGCGTA CTCCATCCATAGCCAAGAACCAAAGGATCCACACGACCTGATGTTTACCATTCAC CGGAGCACAGGCACCATCAGCGTCATCTCCAGCGGCCTGGACCGGGAAAAAGTC CCTGAGTACACACTGACCATCCAGGCCACAGACATGGATGGGGACGGCTCCACC ACCACGGCAGTGGCAGTAGTGGAGATCCTCGATGCCAATGACAATGCTCCCGTGT TTGACCCCCAGAAGTATGAGTCCCATGTGCCTGAGAATGCAGTGGGCCATGAGGT GCAGAGGCTGACGGTCACTGATCTGGACGCCCCCAACTCACCAGCGTGGCGTGCC ACCTACCTCATCGTGGGCGGTGACGACGGGGACCATTTTACCATCGCCACCCACC CTGAGAGCAACCAGGGCATCCTGACAACCAGGAAGGGTTTGGATTTTGAGGCCA AAAACCAGCACACCCTGTACGTTGAAGTGACCAACGAGGCCCCTTTTGTGCTGAA GCTCCCAACCTCAACAGCCACCATAGTGGTCCACGTGGAGGATGTGAATGAGGC ACCCGTGTTTGTCCCGCCCTCCAAAGTCGTTGAGGTCCAGGAGGGCATCCCCACT GGGGAGGCTGTGTGTGTCTACACTGCAAAAGACCCTGACAAGGAGAATCAAAAG ATCAGCTACCGCATCCTGAGAGACCCAGCAGGGTGGCTAGCCATGGACCCAGAC AGTGGGCAGGTCACTGTTGCGGGCACCCTAGACCGTGAGGATGAGCGGTTTGTG AGAAACAACATCTACGAAGTCATGGTCTTGGCTGTGGACAATGGAAGCCCTCCCA CCACTGGCACGGGAACCCTCCTGCTAACACTGATTGATGTCAACGACCATGGCCC AGTCCCTGAGCCCCGTGAGATCACCATCTGCAACCAAAGCCCTGAGTCCCAGGTG CTGAACATCACGGACAAGGACCTGTCCCCCCACACCTCCCCTTTCCAGGCCCAGC TCACAGACGACTCAGACATCTACTGGATGGCAGAGGTCAACGAGAAAGATGACA CGGTGGTCTTGTCCCTGAAGAAGTTCCTGAAGCAGGACACATATGATGTGCACCT TTCTCTGTCTGACCATGGCAACAAGGAGCAGCTGACAGTGATCAGGGCCACCGTG TGTGACTGCCACGGCCATGTCGAGAAATGCCCTGATCCCTGGAAGGGGGGTTTCA TCCTCCCTGTGCTGGGGGCTGTCCTGGCTCTGCTGCTCCTCCTGCTGGTGCTGCTC TTGTTGGTGAGAAAGAAGCGGAAGGTCAAGGAGCCCCTCCTACTCCCAGAAGAT GACACCCGTGACAACGTCTTCTACTACGGCGAAGAGGGGGGTGGCGAAGAGGAC CAGGACTATGACATCACCCAGCTCCACCGAGGTCTGGAGGCCAGGCCGGAGGTG GTTCTCCGCAATGACGTGGCACCAACCTTCATCCCCACACCCATGTACCGTCCTC GGCCAGCCAACCCAGATGAAATCGGCAACTTTATAATCGAGAACCTGAAGGCAG CTAACACGGACCCCACAGCCCCGCCCTACGACTCCCTTTTGGTGTTCGACTATGA GGGCAGCGGCTCCGACGCCGCGTCCCTGAGCTCCCTCACCACCTCCACCTCTGAC CAGGACCAAGATTACGACTATCTGAACGAGTGGGGCAGCCGCTTCAAGAAGCTG GCAGACATGTACGGTGGCGGGGACGACGAC   7 Macaque cynomol aa MGLPRGPLACLLLVQVCWLQCAASEPCRAIFGEAEVTLEAGGAEQEPSQALGKVFM CDH3 gus GCPGQKPALFSTVNDDFTVQNGETVQDRKSLKERNPLKIFPSKRILRRHKRDWVVAPI ECD SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIHTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPVFDPQKYESHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIVGGDDGDHFTIATHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEAV CVYTAKDPDKENQKISYRILRDPAGWLAMDPDSGQVTVAGTLDREDERFVRNNIYE VMVLAVDNGSPPTTGTGTLLLTLIDVNDHGPVPEPREITICNQSPESQVLNITDKDLSP HTSPFQAQLTDDSDIYWMAEVNEKDDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVEKCPDPWKGG   8 Macaque cynomol na ATGGGGCTCCCTCGTGGACCTCTCGCGTGTCTCCTCCTCGTCCAGGTTTGCTGGCT CDH3 gus GCAATGCGCGGCCTCCGAGCCGTGCCGGGCGATCTTCGGGGAGGCTGAAGTGAC ECD CTTGGAGGCGGGAGGCGCGGAGCAGGAGCCCAGCCAGGCCCTGGGGAAAGTATT CATGGGCTGCCCTGGGCAAAAGCCAGCTCTGTTTAGCACTGTTAATGACGACTTC ACTGTGCAGAATGGCGAGACAGTCCAGGACAGAAAGTCACTGAAAGAAAGGAAT CCATTGAAGATCTTCCCATCCAAACGTATCTTACGAAGACACAAGAGAGATTGGG TGGTTGCTCCAATATCTGTCCCTGAAAATGGCAAGGGTCCCTTCCCGCAGAGGCT GAATCAGCTCAAGTCTAATAAAGACAGAGACACGAAGATTTTCTACAGCATCAC GGGGCCGGGGGCAGACAGCCCCCCTGAGGGCGTCTTTGCTGTAGAGAAAGAGAC AGGCTGGTTGTTGTTGAACAAGCCACTGGACCGGGAGGAGATTGCCAAGTATGA GCTCTTTGGCCACGCTGTGTCAGAGAATGGTGCCTCAGTGGAGGATCCCATGAAC ATCTCCATCATCGTGACCGACCAGAATGACCACAAGCCCAAGTTTACCCAGGACA CCTTCCGAGGGAGTGTCTTAGAGGGAGTCCTACCAGGTACTTCTGTGATGCAGGT GACGGCCACAGATGAGGATGATGCCATCCACACCTACAATGGGGTGGTTGCGTA CTCCATCCATAGCCAAGAACCAAAGGATCCACACGACCTGATGTTTACCATTCAC CGGAGCACAGGCACCATCAGCGTCATCTCCAGCGGCCTGGACCGGGAAAAAGTC CCTGAGTACACACTGACCATCCAGGCCACAGACATGGATGGGGACGGCTCCACC ACCACGGCAGTGGCAGTAGTGGAGATCCTCGATGCCAATGACAATGCTCCCGTGT TTGACCCCCAGAAGTATGAGTCCCATGTGCCTGAGAATGCAGTGGGCCATGAGGT GCAGAGGCTGACGGTCACTGATCTGGACGCCCCCAACTCACCAGCGTGGCGTGCC ACCTACCTCATCGTGGGCGGTGACGACGGGGACCATTTTACCATCGCCACCCACC CTGAGAGCAACCAGGGCATCCTGACAACCAGGAAGGGTTTGGATTTTGAGGCCA AAAACCAGCACACCCTGTACGTTGAAGTGACCAATGAGGCCCCTTTTGTGCTGAA GCTCCCAACCTCAACAGCCACCATAGTGGTCCACGTGGAGGATGTGAATGAGGC ACCCGTGTTTGTCCCGCCCTCCAAAGTCGTTGAGGTCCAGGAGGGCATCCCCACT GGGGAGGCTGTGTGTGTCTACACTGCAAAAGACCCTGACAAGGAGAATCAAAAG ATCAGCTACCGCATCCTGAGAGACCCAGCAGGGTGGCTAGCCATGGACCCAGAC AGTGGGCAGGTCACTGTTGCGGGCACCCTAGACCGTGAGGATGAGCGGTTTGTG AGAAACAACATCTACGAAGTCATGGTCTTGGCTGTGGACAATGGAAGCCCTCCCA CCACTGGCACGGGAACCCTCCTGCTAACACTGATTGATGTCAACGACCATGGCCC AGTCCCTGAGCCCCGTGAGATCACCATCTGCAACCAAAGCCCTGAGTCCCAGGTG CTGAACATCACGGACAAGGACCTGTCCCCCCACACCTCCCCTTTCCAGGCCCAGC TCACAGACGACTCAGACATCTACTGGATGGCAGAGGTCAACGAGAAAGATGACA CGGTGGTCTTGTCCCTGAAGAAGTTCCTGAAGCAGGACACATATGATGTGCACCT TTCTCTGTCTGACCATGGCAACAAGGAGCAGCTGACAGTGATCAGGGCCACCGTG TGTGACTGCCACGGCCATGTCGAGAAATGCCCTGATCCCTGGAAGGGGGGT   9 Murine murine aa MELLSGPHAFLLLLLQVCWLRSVVSEPYRAGFIGEAGVTLEVEGTDLEPSQVLGKVA CDH3 LAGQGMHHADNGDIIMLTRGTVQGGKDAMHSPPTRILRRRKREWVMPPIFVPENGK GPFPQRLNQLKSNKDRGTKIFYSITGPGADSPPEGVFTIEKESGWLLLHMPLDREKIVK YELYGHAVSENGASVEEPMNISIIVTDQNDNKPKFTQDTFRGSVLEGVMPGTSVMQV TATDEDDAVNTYNGVVAYSIHSQEPKEPHDLMFTIHKSTGTISVISSGLDREKVPEYR LTVQATDMDGEGSTTTAEAVVQILDANDNAPEFEPQKYEAWVPENEVGHEVQRLTV TDLDVPNSPAWRATYHIVGGDDGDHFTITTHPETNQGVLTTKKGLDFEAQDQHTLY VEVTNEAPFAVKLPTATATVVVHVKDVNEAPVFVPPSKVIEAQEGISIGELVCIYTAQ DPDKEDQKISYTISRDPANWLAVDPDSGQITAAGILDREDEQFVKNNVYEVMVLATD SGNPPTTGTGTLLLTLTDINDHGPIPEPRQIIICNQSPVPQVLNITDKDLSPNSSPFQA QLTHDSDIYWMAEVSEKGDTVALSLKKFLKQDTYDLHLSLSDHGNREQLTMIRATVCD CHGQVFNDCPRPWKGGFILPILGAVLALLTLLLALLLLVRKKRKVKEPLLLPEDDTRD NVFYYGEEGGGEEDQDYDITQLHRGLEARPEVVLRNDVVPTFIPTPMYRPRPANPDEI GNFIIENLKAANTDPTAPPYDSLLVFDYEGSGSDAASLSSLTTSASDQDQDYNYLNEW GSRFKKLADMYGGGEDD  10 Murine murine na ATGGAGCTTCTTAGTGGGCCTCACGCCTTCCTGCTCCTCCTGCTCCAGGTTTGCTG CDH3 GCTACGCAGCGTGGTCTCCGAGCCCTACCGAGCGGGCTTCATCGGGGAGGCTGG AGTGACCTTGGAGGTGGAAGGAACTGACCTGGAGCCGAGCCAAGTTCTGGGGAA AGTAGCCTTGGCTGGACAGGGCATGCACCATGCAGACAATGGAGACATCATTAT GCTGACTAGGGGGACAGTTCAGGGAGGGAAGGATGCGATGCACTCCCCACCCAC CCGCATCTTAAGGAGACGAAAGAGAGAGTGGGTGATGCCACCAATATTCGTCCC CGAGAATGGCAAGGGTCCCTTCCCTCAGAGGCTGAATCAGCTCAAATCTAATAAG GACAGAGGCACCAAGATTTTCTACAGCATCACAGGGCCTGGCGCAGACAGTCCC CCCGAAGGAGTCTTCACCATAGAGAAGGAGTCGGGCTGGCTGTTGTTGCATATGC CACTGGACAGGGAGAAGATTGTCAAGTACGAGCTTTATGGCCACGCTGTATCTGA GAATGGTGCCTCTGTAGAGGAGCCCATGAACATATCCATCATTGTGACAGACCAG AATGACAACAAGCCCAAGTTCACTCAAGACACCTTCAGAGGGAGTGTTCTGGAG GGAGTAATGCCTGGCACTTCTGTGATGCAGGTGACAGCCACAGATGAGGACGAT GCTGTCAACACTTACAATGGGGTGGTGGCTTACTCCATCCATAGCCAAGAGCCGA AGGAGCCACACGACCTCATGTTCACCATCCATAAAAGCACGGGAACCATTAGCG TCATATCCAGTGGCCTGGACCGAGAGAAAGTCCCTGAGTACAGACTGACCGTCCA GGCCACAGACATGGATGGAGAGGGCTCTACCACGACGGCAGAGGCCGTTGTGCA AATCCTTGATGCCAACGATAACGCTCCCGAGTTTGAGCCGCAGAAGTATGAGGCT TGGGTGCCTGAGAACGAAGTGGGCCATGAGGTACAGAGGCTGACAGTGACTGAT CTCGATGTCCCCAACTCGCCAGCGTGGCGTGCCACCTACCACATCGTGGGAGGTG ATGATGGGGACCATTTCACCATCACCACTCACCCAGAGACCAACCAAGGCGTCCT GACAACCAAGAAGGGTTTGGATTTTGAGGCTCAGGACCAACACACCCTGTATGTA GAAGTGACCAACGAGGCTCCCTTTGCAGTGAAGCTCCCGACAGCCACTGCCACCG TGGTGGTCCATGTGAAAGATGTCAACGAAGCCCCTGTGTTTGTTCCACCTTCCAA GGTCATTGAGGCCCAGGAAGGCATCTCTATTGGGGAACTGGTCTGCATCTATACC GCACAGGACCCAGACAAGGAGGACCAGAAGATCAGCTACACCATCTCGAGAGAT CCAGCCAACTGGCTTGCTGTGGACCCAGACAGTGGTCAGATAACTGCCGCAGGC ATCTTGGATCGTGAGGACGAGCAGTTTGTGAAAAACAATGTCTACGAAGTCATGG TTTTGGCCACAGACAGTGGAAACCCTCCCACCACCGGCACTGGGACCCTCCTGCT TACACTTACTGACATCAACGACCATGGCCCGATCCCTGAACCCAGGCAGATCATC ATCTGTAACCAAAGCCCTGTGCCTCAAGTGCTGAACATCACTGACAAGGACCTGT CCCCCAACTCCTCCCCTTTCCAGGCCCAGCTAACACATGACTCAGATATCTACTG GATGGCAGAAGTCAGCGAGAAAGGAGACACCGTGGCCTTGTCCCTGAAGAAGTT CCTGAAACAAGACACGTATGACTTGCATCTTTCTTTGTCTGACCATGGCAACAGG GAACAGCTAACCATGATCAGGGCCACTGTGTGTGACTGCCATGGCCAAGTGTTCA ATGACTGCCCCAGACCCTGGAAGGGTGGTTTCATCCTCCCCATCCTGGGTGCTGT CCTGGCACTGCTGACCCTTCTACTGGCACTCCTCCTGTTGGTGAGGAAGAAGAGG AAGGTCAAAGAGCCCCTTCTGCTCCCAGAAGATGACACGCGAGACAATGTCTTCT ATTATGGAGAAGAGGGTGGTGGTGAAGAGGACCAGGACTATGACATCACCCAAC TCCACCGGGGACTGGAGGCCAGGCCTGAGGTGGTTCTCCGAAACGATGTAGTGC CAACCTTCATCCCCACCCCCATGTACCGACCCCGGCCCGCCAACCCAGATGAAAT CGGGAACTTCATCATCGAGAACCTGAAGGCTGCCAACACTGACCCTACTGCCCCG CCCTACGACTCCCTGCTGGTTTTTGACTACGAGGGCAGCGGCTCTGATGCCGCCT CCCTGAGCTCCCTCACCACCTCCGCCTCCGACCAGGATCAGGACTACAACTACCT TAACGAGTGGGGAAGTCGATTCAAGAAACTGGCGGACATGTATGGTGGCGGTGA GGATGACTAG  11 Murine murine aa EWVMPPIFVPENGKGPFPQRLNQLKSNKDRGTKIFYSITGPGADSPPEGVFTIEKESG CDH3 WLLLHMPLDREKIVKYELYGHAVSENGASVEEPMNISIIVTDQNDNKPKFTQDTFRG ECD SVLEGVMPGTSVMQVTATDEDDAVNTYNGVVAYSIHSQEPKEPHDLMFTIHKSTGTI SVISSGLDREKVPEYRLTVQATDMDGEGSTTTAEAVVQILDANDNAPEFEPQKYEAW VPENEVGHEVQRLTVTDLDVPNSPAWRATYHIVGGDDGDHFTITTHPETNQGVLTTK KGLDFEAQDQHTLYVEVTNEAPFAVKLPTATATVVVHVKDVNEAPVFVPPSKVIEA QEGISIGELVCIYTAQDPDKEDQKISYTISRDPANWLAVDPDSGQITAAGILDREDEQF VKNNVYEVMVLATDSGNPPTTGTGTLLLTLTDINDHGPIPEPRQIIICNQSPVPQVLNI TDKDLSPNSSPFQAQLTHDSDIYWMAEVSEKGDTVALSLKKFLKQDTYDLHLSLSDH GNREQLTMIRATVCDCHGQVFNDCPRPWKGG  12 Murine murine na GAGTGGGTGATGCCACCAATATTCGTCCCCGAGAATGGCAAGGGTCCCTTCCCTC CDH3 AGAGGCTGAATCAGCTCAAATCTAATAAGGACAGAGGCACCAAGATTTTCTACA ECD GCATCACAGGGCCTGGCGCAGACAGTCCCCCCGAAGGAGTCTTCACCATAGAGA AGGAGTCGGGCTGGCTGTTGTTGCATATGCCACTGGACAGGGAGAAGATTGTCA AGTACGAGCTTTATGGCCACGCTGTATCTGAGAATGGTGCCTCTGTAGAGGAGCC CATGAACATATCCATCATTGTGACAGACCAGAATGACAACAAGCCCAAGTTCACT CAAGACACCTTCAGAGGGAGTGTTCTGGAGGGAGTAATGCCTGGCACTTCTGTGA TGCAGGTGACAGCCACAGATGAGGACGATGCTGTCAACACTTACAATGGGGTGG TGGCTTACTCCATCCATAGCCAAGAGCCGAAGGAGCCACACGACCTCATGTTCAC CATCCATAAAAGCACGGGAACCATTAGCGTCATATCCAGTGGCCTGGACCGAGA GAAAGTCCCTGAGTACAGACTGACCGTCCAGGCCACAGACATGGATGGAGAGGG CTCTACCACGACGGCAGAGGCCGTTGTGCAAATCCTTGATGCCAACGATAACGCT CCCGAGTTTGAGCCGCAGAAGTATGAGGCTTGGGTGCCTGAGAACGAAGTGGGC CATGAGGTACAGAGGCTGACAGTGACTGATCTCGATGTCCCCAACTCGCCAGCGT GGCGTGCCACCTACCACATCGTGGGAGGTGATGATGGGGACCATTTCACCATCAC CACTCACCCAGAGACCAACCAAGGCGTCCTGACAACCAAGAAGGGTTTGGATTTT GAGGCTCAGGACCAACACACCCTGTATGTAGAAGTGACCAACGAGGCTCCCTTTG CAGTGAAGCTCCCGACAGCCACTGCCACCGTGGTGGTCCATGTGAAAGATGTCAA CGAAGCCCCTGTGTTTGTTCCACCTTCCAAGGTCATTGAGGCCCAGGAAGGCATC TCTATTGGGGAACTGGTCTGCATCTATACCGCACAGGACCCAGACAAGGAGGAC CAGAAGATCAGCTACACCATCTCGAGAGATCCAGCCAACTGGCTTGCTGTGGACC CAGACAGTGGTCAGATAACTGCCGCAGGCATCTTGGATCGTGAGGACGAGCAGT TTGTGAAAAACAATGTCTACGAAGTCATGGTTTTGGCCACAGACAGTGGAAACCC TCCCACCACCGGCACTGGGACCCTCCTGCTTACACTTACTGACATCAACGACCAT GGCCCGATCCCTGAACCCAGGCAGATCATCATCTGTAACCAAAGCCCTGTGCCTC AAGTGCTGAACATCACTGACAAGGACCTGTCCCCCAACTCCTCCCCTTTCCAGGC CCAGCTAACACATGACTCAGATATCTACTGGATGGCAGAAGTCAGCGAGAAAGG AGACACCGTGGCCTTGTCCCTGAAGAAGTTCCTGAAACAAGACACGTATGACTTG CATCTTTCTTTGTCTGACCATGGCAACAGGGAACAGCTAACCATGATCAGGGCCA CTGTGTGTGACTGCCATGGCCAAGTGTTCAATGACTGCCCCAGACCCTGGAAGGG TGGT  13 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom1 mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKREWVMPPI (aa 108- FVPENGKGPFPQRLNQLKSNKDRGTKIFYSITGPGADSPPEGVFTIEKESGWLLLHMP 215) LDREKIVKYELYGHAVSENGASVEEPMNISIIVTDQNDNKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  14 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom1A mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKREWVMPPI (aa 108- FVPENGKGPFPQRLNQLKSNKDRGTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 143) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  15 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom1B mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 144- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFTIEKESGWLLLHMP 179) LDREKIVKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  16 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom1C mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 180- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 215) LDREEIAKYELYGHAVSENGASVEEPMNISIIVTDQNDNKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  17 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom2 mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 216- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 327) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVMP GTSVMQVTATDEDDAVNTYNGVVAYSIHSQEPKEPHDLMFTIHKSTGTISVISSGLDR EKVPEYRLTVQATDMDGEGSTTTAEAVVQILDANDNAPEFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  18 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom2A mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 216- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 252) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVMP GTSVMQVTATDEDDAVNTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  19 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom2B mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 253- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 290) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKEPHDLMFTIHKSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  20 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom2C mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 291- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 327) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYRLTVQATDMDGEGSTTTAEAVVQILDANDNAPEFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  21 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom3mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 328- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 440) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFEPQKYEAWVPENEVGH EVQRLTVTDLDVPNSPAWRATYHIVGGDDGDHFTITTHPETNQGVLTTKKGLDFEAQ DQHTLYVEVTNEAPFAVKLPTATATVVVHVKDVNEAPVFVPPSKVVEVQEGIPTGEP VCVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIY EVMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDL SPHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQ LTVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRK KRMAKYEKAEIKEMGEMHRELNA  22 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom3A mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 328- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 363) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFEPQKYEAWVPENEVGH EVQRLTVTDLDVPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  23 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom3B mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 364- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 403) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYHIVGGDDGDHFTITTHPETNQGVLTTKKGLDFEAQ DQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  24 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom3C mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 404- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 440) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFAVKLPTATATVVVHVKDVNEAPVFVPPSKVVEVQEGIPTGEP VCVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIY EVMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDL SPHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQ LTVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRK KRMAKYEKAEIKEMGEMHRELNA  25 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom4 mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 441- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 546) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVIEAQEGISIGELVC IYTAQDPDKEDQKISYTISRDPANWLAVDPDSGQITAAGILDREDEQFVKNNVYEVM VLATDSGNPPTTGTGTLLLTLTDINDHGPVPEPRQITICNQSPVRQVLNITDKDLSPHT SPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQLTVI RATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKKRM AKYEKAEIKEMGEMHRELNA  26 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom4A mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 441- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 474) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVIEAQEGISIGELVC IYTAQDPDKEDQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYEV MVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLSP HTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  27 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom4B mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 475- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 511) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYTISRDPANWLAVDPDSGQITAAGILDREDEQFVKNNIYEV MVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLSP HTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  28 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom4C mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 512- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 546) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNVYE VMVLATDSGNPPTTGTGTLLLTLTDINDHGPVPEPRQITICNQSPVRQVLNITDKDLSP HTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQL TVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  29 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom5 mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 547- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 650) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPIPEPRQIIICNQSPVPQVLNITDKDLSP NSSPFQAQLTHDSDIYWMAEVSEKGDTVALSLKKFLKQDTYDLHLSLSDHGNREQL TMIRATVCDCHGQVFNDCPRPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISR KKRMAKYEKAEIKEMGEMHRELNA  30 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom5A mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 547- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 581) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPIPEPRQIIICNQSPVPQVLNITDKDLSP NSSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDVHLSLSDHGNKEQLT VIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRKK RMAKYEKAEIKEMGEMHRELNA  31 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom5B mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 582- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 616) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTHDSDIYWMAEVSEKGDTVALSLKKFLKQDTYDVHLSLSDHGNKEQ LTVIRATVCDCHGHVETCPGPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISRK KRMAKYEKAEIKEMGEMHRELNA  32 Hu CDH3 chimeric aa MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFM Dom5C mu hu/mu GCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI (aa 617- SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKP 650) LDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLP GTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDR EKVPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGH EVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAK NQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPV CVYTAEDPDKENQKISYRILRDPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYE VMVLAMDNGSPPTTGTGTLLLTLIDVNDHGPVPEPRQITICNQSPVRQVLNITDKDLS PHTSPFQAQLTDDSDIYWTAEVNEEGDTVVLSLKKFLKQDTYDLHLSLSDHGNREQL TMIRATVCDCHGQVFNDCPRPWKGGSGGGGSGAGVIAVIVVVVIAIVAGIVVLVISR KKRMAKYEKAEIKEMGEMHRELNA  33 Human human aa SITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIA epitope cluster D1B  34 Human human aa VPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPM epitope cluster D2C  35 Human human aa FDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSPAWR epitope cluster D3A  36 Human human aa VPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEV epitope QRLTVTDLDAPNSPAWR clusters D2C + D3A  37 Macaque cynomol aa SITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIA epitope gus cluster D1B  38 Macaque cynomol aa VPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPV epitope gus cluster D2C  39 Macaque cynomol aa FDPQKYESHVPENAVGHEVQRLTVTDLDAPNSPAWR epitope gus cluster D3A  40 Macaque cynomol aa VPEYTLTIQATDMDGDGSTTTAVAVVEILDANDNAPVFDPQKYESHVPENAVGHEV epitope gus QRLTVTDLDAPNSPAWR clusters D2C + D3A  41 Human human aa MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNF CDH1 (E- EDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKV cad.) TLNTVGHHHRPPPHQASVSGIQAELLTFPNSSPGLRRQKRDWVIPPISCPENEKGPFPK NLVQIKSNKDKEGKVFYSITGQGADTPPVGVFIIERETGWLKVTEPLDRERIATYTLFS HAVSSNGNAVEDPMEILITVTDQNDNKPEFTQEVFKGSVMEGALPGTSVMEVTATD ADDDVNTYNAAIAYTILSQDPELPDKNMFTINRNTGVISVVTTGLDRESFPTYTLVVQ AADLQGEGLSTTATAVITVTDTNDNPPIFNPTTYKGQVPENEANVVITTLKVTDADAP NTPAWEAVYTILNDDGGQFVVTTNPVNNDGILKTAKGLDFEAKQQYILHVAVTNVV PFEVSLTTSTATVTVDVLDVNEAPIFVPPEKRVEVSEDFGVGQEITSYTAQEPDTFME QKITYRIWRDTANWLEINPDTGAISTRAELDREDFEHVKNSTYTALIIATDNGSPVAT GTGTLLLILSDVNDNAPIPEPRTIFFCERNPKPQVINIIDADLPPNTSPFTAELTHGAS ANWTIQYNDPTQESIILKPKMALEVGDYKINLKLMDNQNKDQVTTLEVSVCDCEGAAG VCRKAQPVEAGLQIPAILGILGGILALLILILLLLLFLRRRAVVKEPLLPPEDDTRDNV YYYDEEGGGEEDQDFDLSQLHRGLDARPEVTRNDVAPTLMSVPRYLPRPANPDEIGNF IDENLKAADTDPTAPPYDSLLVFDYEGSGSEAASLSSLNSSESDKDQDYDYLNEWGN RFKKLADMYGGGEDD  42 Human human aa MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEGQPLLN CDH2 (N- VKFSNCNGKRKVQYESSEPADFKVDEDGMVYAVRSFPLSSEHAKFLIYAQDKETQE cad.) KWQVAVKLSLKPTLTEESVKESAEVEEIVFPRQFSKHSGHLQRQKRDWVIPPINLPEN SRGPFPQELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDREQI ARFHLRAHAVDINGNQVENPIDIVINVIDMNDNRPEFLHQVWNGTVPEGSKPGTYVMTV TAIDADDPNALNGMLRYRIVSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTL IIQATDMEGNPTYGLSNTATAVITVTDVNDNPPEFTAMTFYGEVPENRVDIIVANLTV TDKDQPHTPAWNAVYRISGGDPTGRFAIQTDPNSNDGLVTVVKPIDFETNRMFVLTV AAENQVPLAKGIQHPPQSTATVSVTVIDVNENPYFAPNPKIIRQEEGLHAGTMLTTFT AQDPDRYMQQNIRYTKLSDPANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLA SDNGIPPMSGTGTLQIYLLDINDNAPQVLPQEAETCETPDPNSINITALDYDIDPNAGP FAFDLPLSPVTIKRNWTITRLNGDFAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISI LRVKVCQCDSNGDCTDVDRIVGAGLGTGAIIAILLCIIILLILVLMFVVWMKRRDKERQ AKQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQLQQPDTVEPDAIKPVGIRRMDERP IHAEPQYPVRSAAPHPGDIGDFINEGLKAADNDPTAPPYDSLLVFDYEGSGSTAGSLSS LNSSSSGGEQDYDYLNDWGPRFKKLADMYGGGDD  43 Human human aa MTAGAGVLLLLLSLSGALRAHNEDLTTRETCKAGFSEDDYTALISQNILEGEKLLQV CDH4 (R- KFSSCVGTKGTQYETNSMDFKVGADGTVFATRELQVPSEQVAFTVTAWDSQTAEK cad.) WDAVVRLLVAQTSSPHSGHKPQKGKKVVALDPSPPPKDTLLPWPQHQNANGLRRR KRDWVIPPINVPENSRGPFPQQLVRIRSDKDNDIPIRYSITGVGADQPPMEVFSIDSMS GRMYVTRPMDREEHASYHLRAHAVDMNGNKVENPIDLYIYVIDMNDNRPEFINQVY NGSVDEGSKPGTYVMTVTANDADDSTTANGMVRYRIVTQTPQSPSQNMFTINSETG DIVTVAAGLDREKVQQYTVIVQATDMEGNLNYGLSNTATAIITVTDVNDNPPEFTAS TFAGEVPENRVETVVANLTVMDRDQPHSPNWNAVYRIISGDPSGHFSVRTDPVTNEG MVTVVKAVDYELNRAFMLTVMVSNQAPLASGIQMSFQSTAGVTISIMDINEAPYFPS NHKLIRLEEGVPPGTVLTTFSAVDPDRFMQQAVRYSKLSDPASWLHINATNGQITTA AVLDRESLYTKNNVYEATFLAADNGIPPASGTGTLQIYLIDINDNAPELLPKEAQICEK PNLNAINITAADADVDPNIGPYVFELPFVPAAVRKNWTITRLNGDYAQLSLRILYLEA GMYDVPIIVTDSGNPPLSNTSIIKVKVCPCDDNGDCTTIGAVAAAGLGTGAIVAILICI LILLTMVLLFVMWMKRREKERHTKQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQ LQQPEAMGHVPSKAPGVRRVDERPVGAEPQYPIRPMVPHPGDIGDFINEGLRAADND PTAPPYDSLLVFDYEGSGSTAGSVSSLNSSSSGDQDYDYLNDWGPRFKKLADMYGG GEED  44 Human human aa MQRLMMLLATSGACLGLLAVAAVAAAGANPAQRDTHSLLPTHRRQKRDWIWNQM CDH5 HIDEEKNTSLPHHVGKIKSSVSRKNAKYLLKGEYVGKVFRVDAETGDVFAIERLDRE (VE-cad) NISEYHLTAVIVDKDTGENLETPSSFTIKVHDVNDNWPVFTHRLFNASVPESSAVGTS VISVTAVDADDPTVGDHASVMYQILKGKEYFAIDNSGRIITITKSLDREKQARYEIVV EARDAQGLRGDSGTATVLVTLQDINDNFPFFTQTKYTFVVPEDTRVGTSVGSLFVED PDEPQNRMTKYSILRGDYQDAFTIETNPAHNEGIIKPMKPLDYEYIQQYSFIVEATDPT IDLRYMSPPAGNRAQVIINITDVDEPPIFQQPFYHFQLKENQKKPLIGTVLAMDPDAAR HSIGYSIRRTSDKGQFFRVTKKGDIYNEKELDREVYPWYNLTVEAKELDSTGTPTGKE SIVQVHIEVLDENDNAPEFAKPYQPKVCENAVHGQLVLQISAIDKDITPRNVKFKFILN TENNFTLTDNHDNTANITVKYGQFDREHTKVHFLPVVISDNGMPSRTGTSTLTVAVC KCNEQGEFTFCEDMAAQVGVSIQAVVAILLCILTITVITLLIFLRRRLRKQARAHGKSV PEIHEQLVTYDEEGGGEMDTTSYDVSVLNSVRRGGAKPPRPALDARPSLYAQVQKPP RHAPGAHGGPGEMAAMIEVKKDEADHDGDGPPYDTLHIYGYEGSESIAESLSSLGTD SSDSDVDYDFLNDWGPRFKMLAELYGSDPREELLY  45 Macaque cynomol aa MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVSF CDH1 gus EDCTGRQRTAYFSLDTRFKVGPDGVITVKRPLQFHNPQIHFLVYAWDSTYRKFSTKV TLNTVGHHSRTPPLHASVSGVQAELLTFPNSSPGLRRWKRDWVIPPISCPENEKGPFP KNLVQIKSNKDKEGKVFYSITGQGADTPPVGVFIIERETGWLKVTEPLDRENIATYTL FSHAVSSNGNAVEDPMEILITVTDQNDNKPVFTQEVFKGSVMEGALPGTSVMEVTAT DADDDVNTYNAAIAYSILSQDPELPDKNMFTINKNTGVISVVTTGLDRESFPMYTLV VQAADLQGEGLSTTATAVITVTDTNDNPPVFNPTTYKGQVPENQANFVITTLKVTDA DAPNTPAWEAVYTILNDNDGQFVVTTNPVTNDGILKTAKGLDFEAKQQYILHVAVT NVAPFEVSLTTSTATVTVDVLDVNEAPIFVPPEKRVEVSEDFGVGQEITSYTAREPDTF MEQKITYRIWRDAANWLEINPDTGAISTRAELDREDVEHVKNSTYTALIIATDNDHHL CDFLESHFLDEEVKLIKKIAQESIILKPKIALEVGDYKINLKLMDNQKKDQVTTLEVSV CDCEGAAGICKKAPLVEAGMQIPAILGILGGILALLILILLLLLFLRRRAVVKEPLLPP EDDTRDNVYYYDEEGGGEEDQDFDLSQLHRGLDARPEVTRNDVAPTLLSVPRYLPRP ANPDEIGNFIDENLKAADSDPTAPPYDSLLVFDYEGSGSEAASLSSLNSSESDKDQDY DYLNEWGNRFKKLADMYGGGEDD  46 Macaque cynomol aa MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEGQPLLN CDH2 gus VKFSNCNGKRKVQYESSEPADFKVDEDGMVYAVRSFPLSSEHAKFLIYAQDKETQE KWQVAVKLSLKPALTEESVKEPPEVEEIVFPRQLSKHSGHLQRQKRDWVIPPINLPEN SRGPFPQELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDREQI ARFHLRAHAVDINGNQVENPIDIVINVIDMNDNRPEFLHQVWNGTVPEGSKPGTYVMTV TAIDADDPNALNGMLRYRILSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTLI IQATDMEGNPTYGLSNTATAIITVTDVNDNPPEFTAMTFYGEVPENRVDVIVANLTVT DKDQPHTPAWNAVYRISGGDPTGRFAIQTDPNSNDGLVTVVKPIDFETNRMFVLTVA AENQVPLAKGIQHPPQSTATVSVTVIDVNENPYFAPNPKIIRQEEGLHAGTMLTTFTA QDPDRYMQQNIRYTKLSDPANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLAS DNGIPPMSGTGTLQIYLLDINDNAPQVLPQEAETCETPDPNSINITALDYDIDPNAGPF AFDLPLSPVTIKRNWTITRLNGDFAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISIL RVKVCQCDSNGDCTDVDRIVGAGLGTGAIIAILLCIIILLILVLMFVVWMKRRDKERQA KQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQLQQPDTVEPDAIKPVGIRRMDERP IHAEPQYPVRSAAPHPGDIGDFINEGLKAADNDPTAPPYDSLLVFDYEGSGSTAGSL SSLNSSSSGGEQDYDYLNDWGPRFKKLADMYGGGDD  47 Macaque cynomol aa MTAGAGVLLLLLSLSGALRAHNEDLTTRETCKAGFSEDDYTALISQNILEGEKLLQV CDH4 gus KFSSCVGTKGTQYETNSVDFKVGSDGTVFATRELQVPSEQVAFTVTAWDSQTAERW DAVVRLLVAQTSSLHSGHKPQKGKKIVALDPSPPPKDTLLPWPRHQNADGLRRRKR DWVIPPINVPENSRGPFPQQLVRIRSDKDNDIPIRYSITGVGADQPPMEVFSIDSMSGR MYVTRPMDREEHASYHLRAHAVDMNGNKVENPIDLYIYVIDMNDNRPEFINQVYNG SVDEGSKPGEAFSFSTRLSSPNTTTAPGNGDSHHVVTRRPRGGQGLGTQTCAAGDIVS LSRGMSREAKVQQYTVIVQATDMEGNLNYGLSNTATAIITVTDVNDNPPEFTASTFA GEVPENRVETVVANLTVMDRDQPHSPNWNAVYRIISGDPSGHFSVRTDPVTNEGMV TVVKAVDYELNRAFMLTVMVSNQAPLASGIQMSFQSTAGVTISVMDINEAPYFPSNH KLIRLEEGVPPGTVLTTFSAVDPDRFMQQAVRYSKLSDPANWLHINTTNGQITTAAV LDRESLYTKNNVYEATFLAADNGIPPASGTGTLQIYLIDINDNAPELLPKEAQICEKPN LNAINITAADADVDPNIGPYVFELPFVPAAVRKNWTITRLNGDYAQLSLRILYLEAGM YDVPIIVTDSGNPPLSNTSIIKVKVCPCDDNGDCTTIGAVAAAGLGTGAIVAILICILI LLTMVLLFVMWMKRREKERHTKQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQLQ QPEAMGHVPSKAPGVRRVDERPVGAEPQYPVRPMVPHPGDIGDFINEGLRAADNDP TAPPYDSLLVFDYEGSGSTAGSVSSLNSSSSGDQDYDYLNDWGPRFKKLADMYGGG EED  48 Macaque cynomol aa MQRLMMLVATSGACLGLLAAAAAAAAAGANPAQRDTPSLLPTHRRQKRDWIWNQ CDH5 gus MHIDEEKNTSLPHHVGKIKSSVSRKNAKYLLKGEFVDKVFRVDAETGDVFAIERLDR ENISEYHLTAVIVDKDTGENLETPSSFTIKVHDVNDNWPVFTHRLFNASVPESSAVGT SVISVTAVDADDPTVGDHASVMYQILKGKEYFAIDNSGRIVTITKSLDREKQARYEIV VEARDAQGLRGDSGTATVLVTLQDINDNFPFFTQTKYTFVVPEDTRVGTSVGSLFVE DPDEPQNRMTKYSILRGDYQDAFTIETNPTHNEGIIKPMKPLDYEYIQQYSFIVEATDP TIDLRYLSPPAGNRAQVIINITDVDEPPIFQQPFYHFQLKENQKKPLIGTVLAMDPDAA RHSIGYSIRRTSDKGQFFRVTKKGDIYNEKELDREVYPWYNLTVEAKELDSTGTPTG KESIVQVHIEVLDENDNAPEFAQPYQPKVCENAAHGQLVLQISAIDKDITPRNVKFKF TLNTENNFTLTDNHDNTANITVKYGQFDREHTKVHFLPVVISDNGMPSRTGTSTLTV AVCKCNEQGEFTFCEDMAAQVGVSIQAVVAILLSILTITVIALLIFLRRRLRKQARAHG KSVPEIHEQLVTYDEEGGGEMDTTSYDVSVLNSVRRGGAKPPRPALDARPSLYAQVQ KPPRHAPGAHGGPGEMAAMIEVKKDEADHDGDGPPYDTLHIYGYEGSESIAESLSSL GTDSSDSDVDYDFLNDWGPRFKMLAELYGSDPREELLY  49 D1B CDH3-1 VH aa SYAMS CDR1  50 VH aa TISSGGHYTYYPDSVKG CDR2  51 VH aa YYYGIPFGY CDR3  52 VL aa RASQDIGINLI CDR1  53 VL aa DTSSLDS CDR2  54 VL aa LQYGSSPLT CDR3  55 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSTISSGGHY TYYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGTL VTVSS  56 VL aa DIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQQKPGKAPKRLIYDTSSLDSGVP SRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPLTFGGGTKVEIK  57 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSTISSGGHY TYYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGTL VTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQQ KPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPLT FGGGTKVEIK  58 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSTISSGGHY specific TYYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGTL molecule VTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQQ KPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPLT FGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT VSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL  59 D1B CDH3-2 VH aa SYAMS CDR1  60 VH aa TISSGGHYTYYPDSVKG CDR2  61 VH aa YYYGIPFGY CDR3  62 VL aa RASQDIGINLI CDR1  63 VL aa DTSSLDS CDR2  64 VL aa LQYGSSPLT CDR3  65 VH aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT LVTVSS  66 VL aa DIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQQKPGKAPKRLIYDTSSLDSGVP SRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPLTFGGGTKVEIK  67 scFv aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQ QKPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPL TFGGGTKVEIK  68 bi- aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH specific YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT molecule LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQ QKPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPL TFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ APGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL  69 D1B CDH3-3 VH aa SYAMS CDR1  70 VH aa TISSGGHYTYYPDSVKG CDR2  71 VH aa YYYGIPFGY CDR3  72 VL aa RASQDIGINLI CDR1  73 VL aa DTSSLDS CDR2  74 VL aa LQYGSSPLT CDR3  75 VH aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT LVTVSS  76 VL aa DIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQQKPGKAPKRLIYDTSSLDSGVP SRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPLTFGGGTKVEIK  77 scFv aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQ QKPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPL TFGGGTKVEIK  78 bi- aa EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVATISSGGH specific YTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYYYGIPFGYWGQGT molecule LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSTLSASLGDRVTITCRASQDIGINLIWLQ QKPGKAPKRLIYDTSSLDSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLQYGSSPL TFGGGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWVRQ APGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDTAV YYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSG SLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL  79 D1B CDH3-4 VH aa SSWMN CDR1  80 VH aa RIYPGDGETKYADSVKG CDR2  81 VH aa QRDYGALYAMDY CDR3  82 VL aa RVSDDIYSYLA CDR1  83 VL aa NAKTLAE CDR2  84 VL aa QNHYVTPFT CDR3  85 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSWMNWVRQAPGKGLEWVSRIYPGDG ETKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKQRDYGALYAMDYW GQGTLVTVSS  86 VL aa DIQLTQSPSFLSASVGDRVTITCRVSDDIYSYLAWYQQKPGKAPKLLIYNAKTLAEGV PSRFSGSGSGTEFTLTISSLQPEDFATYYCQNHYVTPFTFGQGTKLEIK  87 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSWMNWVRQAPGKGLEWVSRIYPGDG ETKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKQRDYGALYAMDYW GQGTLVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRVSDDIYSYL AWYQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQNH YVTPFTFGQGTKLEIK  88 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSWMNWVRQAPGKGLEWVSRIYPGDG specific ETKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKQRDYGALYAMDYW molecule GQGTLVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRVSDDIYSYL AWYQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQNH YVTPFTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVT QEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPA RFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL  89 D1B CDH3-5 VH aa TSWMN CDR1  90 VH aa RIYPGDGETKYNGKFKG CDR2  91 VH aa QRDYGALYALDY CDR3  92 VL aa RASENIYSYLA CDR1  93 VL aa NAKTLAE CDR2  94 VL aa QHHYVPPYT CDR3  95 VH aa EVQLVEQSGAELVKPGASVKISCKASGYAFSTSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYALDY WGQGTRVTVSS  96 VL aa ELMMTQTPASLSASVGETVTFTCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLAE GVPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYVPPYTFGGGTKLEIK  97 scFv aa EVQLVEQSGAELVKPGASVKISCKASGYAFSTSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYALDY WGQGTRVTVSSGGGGSGGGGSGGGGSELMMTQTPASLSASVGETVTFTCRASENIY SYLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYY CQHHYVPPYTFGGGTKLEIK  98 bi- aa EVQLVEQSGAELVKPGASVKISCKASGYAFSTSWMNWVKQRPGKGLEWIGRIYPGD specific GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYALDY molecule WGQGTRVTVSSGGGGSGGGGSGGGGSELMMTQTPASLSASVGETVTFTCRASENIY SYLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYY CQHHYVPPYTFGGGTKLEIKRTGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN KYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHH HHHH  99 D1B CDH3-6 VH aa SSWMN CDR1 100 VH aa RIYPGDGETKYNGKFKG CDR2 101 VH aa QRDYGALYAMDY CDR3 102 VL aa RASDDIYSYLA CDR1 103 VL aa NAKTLAE CDR2 104 VL aa QNHYVTPFT CDR3 105 VH aa EVQLVEESGPELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYAMDY WGQGTSVTVSS 106 VL aa ELVMTQSPASLSASVGETVTITCRASDDIYSYLAWYQQKQGKSPQLLVYNAKTLAEG VPSRFSGSGSGTQFSLKINSLQPEDFGTYYCQNHYVTPFTFGAGTKLEIK 107 scFv aa EVQLVEESGPELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYAMDY WGQGTSVTVSSGGGGSGGGGSGGGGSELVMTQSPASLSASVGETVTITCRASDDIYS YLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGTYYC QNHYVTPFTFGAGTKLEIK 108 bi- aa EVQLVEESGPELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD specific GETKYNGKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARQRDYGALYAMDY molecule WGQGTSVTVSSGGGGSGGGGSGGGGSELVMTQSPASLSASVGETVTITCRASDDIYS YLAWYQQKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGTYYC QNHYVTPFTFGAGTKLEIKRTGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHH HH 109 D1B CDH3-7 VH aa SSWMN CDR1 110 VH aa RIYPGDGETKYNGKFKG CDR2 111 VH aa QRDYGALYAMDY CDR3 112 VL aa RLSENIYSYLA CDR1 113 VL aa NSKTLAE CDR2 114 VL aa QNHYGFPFT CDR3 115 VH aa EVQLVEQSGAELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSTLTSEDSAVYFCARQRDYGALYAMDY WGQGTSVTVSS 116 VL aa ELQMTQSPASLSASVGETVTITCRLSENIYSYLAWYRQKEGESPQLLVYNSKTLAEGV PSRFSGSGSGTQFSLKINSLQPEDFGNYYCQNHYGFPFTFGAGTKLEIK 117 scFv aa EVQLVEQSGAELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD GETKYNGKFKGKATLTADKSSSTAYMQLSTLTSEDSAVYFCARQRDYGALYAMDY WGQGTSVTVSSGGGGSGGGGSGGGGSELQMTQSPASLSASVGETVTITCRLSENIYS YLAWYRQKEGESPQLLVYNSKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGNYYC QNHYGFPFTFGAGTKLEIK 118 bi- aa EVQLVEQSGAELVKPGASVKISCKASGYAFSSSWMNWVKQRPGKGLEWIGRIYPGD specific GETKYNGKFKGKATLTADKSSSTAYMQLSTLTSEDSAVYFCARQRDYGALYAMDY molecule WGQGTSVTVSSGGGGSGGGGSGGGGSELQMTQSPASLSASVGETVTITCRLSENIYS YLAWYRQKEGESPQLLVYNSKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGNYYC QNHYGFPFTFGAGTKLEIKRTGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHH HH 119 D1B CDH3-8 VH aa SYWMN CDR1 120 VH aa HIYPGDGDTNYNGKFKG CDR2 121 VH aa DRGSFGAWFAY CDR3 122 VL aa RASQDISNYLN CDR1 123 VL aa YTSRLHS CDR2 124 VL aa QQGNRNPPT CDR3 125 VH aa EVQLVEQSGAEVVKPGASVKITCKASGYAFSSYWMNWVRQRPGKGLEWIGHIYPGD GDTNYNGKFKGKVTLTADKSSNTAYMQLSDLTPEDSAVYFCARDRGSFGAWFAYW GQGTTVTVSS 126 VL aa ELVMTQTPSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLHSGV PSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNRNPPTFGGGTKLEIK 127 scFv aa EVQLVEQSGAEVVKPGASVKITCKASGYAFSSYWMNWVRQRPGKGLEWIGHIYPGD GDTNYNGKFKGKVTLTADKSSNTAYMQLSDLTPEDSAVYFCARDRGSFGAWFAYW GQGTTVTVSSGGGGSGGGGSGGGGSELVMTQTPSSLSASLGDRVTISCRASQDISNYL NWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQG NRNPPTFGGGTKLEIK 128 bi- aa EVQLVEQSGAEVVKPGASVKITCKASGYAFSSYWMNWVRQRPGKGLEWIGHIYPGD specific GDTNYNGKFKGKVTLTADKSSNTAYMQLSDLTPEDSAVYFCARDRGSFGAWFAYW molecule GQGTTVTVSSGGGGSGGGGSGGGGSELVMTQTPSSLSASLGDRVTISCRASQDISNYL NWYQQKPDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQG NRNPPTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYA MNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 129 D1B CDH3-9 VH aa TYGMS CDR1 130 VH aa TISSGGHYSYYPDSVKG CDR2 131 VH aa YYYGSPFAY CDR3 132 VL aa RASQDIGSSLN CDR1 133 VL aa DTSSLDS CDR2 134 VL aa VQYGSSPLT CDR3 135 VH aa EVQLVEESGGDLVKPGGSLKLSCAASGFTFSTYGMSWVRQTPDKRLEWVATISSGG HYSYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGSPFAYWGQG TTVTVSS 136 VL aa ELQMTQSPSSLSASLGERVSLTCRASQDIGSSLNWLQQKPDGTIKRLIYDTSSLDSGVP KRFSGSRSGSDYSLTISSLESEDFGDYYCVQYGSSPLTFGAGTKLEIK 137 scFv aa EVQLVEESGGDLVKPGGSLKLSCAASGFTFSTYGMSWVRQTPDKRLEWVATISSGG HYSYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGSPFAYWGQG TTVTVSSGGGGSGGGGSGGGGSELQMTQSPSSLSASLGERVSLTCRASQDIGSSLNW LQQKPDGTIKRLIYDTSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFGDYYCVQYGSS PLTFGAGTKLEIK 138 bi- aa EVQLVEESGGDLVKPGGSLKLSCAASGFTFSTYGMSWVRQTPDKRLEWVATISSGG specific HYSYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGSPFAYWGQG molecule TTVTVSSGGGGSGGGGSGGGGSELQMTQSPSSLSASLGERVSLTCRASQDIGSSLNW LQQKPDGTIKRLIYDTSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFGDYYCVQYGSS PLTFGAGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVT QEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPA RFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 139 D1B CDH3-10 VH aa SYAMS CDR1 140 VH aa TISSGGHYTYYPDSVKG CDR2 141 VH aa YYYGIPFGY CDR3 142 VL aa RASQDIGINLI CDR1 143 VL aa DTSSLDS CDR2 144 VL aa LQYGSSPLT CDR3 145 VH aa EVQLVEESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPDKRLEWVATISSGGH YTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGIPFGYWGQGT TVTVSS 146 VL aa ELVMTQSPSSLSASLGEGVSLTCRASQDIGINLIWLRQEPDGTIKRLIYDTSSLDSGVP KRFSGSRSGSDYSLTISSLESEDFVHYYCLQYGSSPLTFGAGTKLEIK 147 scFv aa EVQLVEESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPDKRLEWVATISSGGH YTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGIPFGYWGQGT TVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLSASLGEGVSLTCRASQDIGINLIWLR QEPDGTIKRLIYDTSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFVHYYCLQYGSSPL TFGAGTKLEIK 148 bi- aa EVQLVEESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPDKRLEWVATISSGGH specific YTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCASYYYGIPFGYWGQGT molecule TVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLSASLGEGVSLTCRASQDIGINLIWLR QEPDGTIKRLIYDTSSLDSGVPKRFSGSRSGSDYSLTISSLESEDFVHYYCLQYGSSPL TFGAGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVR QAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTA VYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSG SLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 149 D2C CDH3-11 VH aa SYPIN CDR1 150 VH aa VIWTGGGTNYASSVKG CDR2 151 VH aa SRGVYDFDGRGAMDY CDR3 152 VL aa KSSQSLLYSSNQKNYLA CDR1 153 VL aa WASTRES CDR2 154 VL aa QQYYSYPYT CDR3 155 VH aa EVQLLESGGGLVQPGGSLRLSCAVSGFTLSSYPINWVRQAPGKGLEWVSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSS 156 VL aa DIVMTQSPDSLAVSVGERVTINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 157 scFv aa EVQLLESGGGLVQPGGSLRLSCAVSGFTLSSYPINWVRQAPGKGLEWVSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSVGERVTINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIK 158 bi- aa EVQLLESGGGLVQPGGSLRLSCAVSGFTLSSYPINWVRQAPGKGLEWVSVIWTGGGT specific NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSVGERVTINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 159 D2C CDH3-12 VH aa SYPIN CDR1 160 VH aa VIWTGGGTNYNPSLKS CDR2 161 VH aa SRGVYDFDGRGAMDY CDR3 162 VL aa KSSQSLLYSSNQKNYLA CDR1 163 VL aa WASTRES CDR2 164 VL aa QQYYSYPYT CDR3 165 VH aa QVQLQESGPGLVKPSETLSLTCTVSGVSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSS 166 VL aa DIVMTQSPASLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 167 scFv aa QVQLQESGPGLVKPSETLSLTCTVSGVSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPASLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIK 168 bi- aa QVQLQESGPGLVKPSETLSLTCTVSGVSITSYPINWIRQPPGKGLEWIGVIWTGGGTN specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG molecule QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPASLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTF NSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 169 D2C CDH3-13 VH aa SYPIN CDR1 170 VH aa VIWTGGGTNYASSVKG CDR2 171 VH aa SRGVYDFDGRGAMDY CDR3 172 VL aa KSSQSLLYSSNQKNYFA CDR1 173 VL aa WASTRES CDR2 174 VL aa QQYYSYPYT CDR3 175 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSS 176 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 177 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIK 178 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT specific NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 179 D2C CDH3-14 VH aa SYPIN CDR1 180 VH aa VIWTGGGTNYNPSLKS CDR2 181 VH aa SRGVYDFDGRGAMDY CDR3 182 VL aa KSSQSLLYSSNQKNYLA CDR1 183 VL aa WASTRES CDR2 184 VL aa QQYYSYPYT CDR3 185 VH aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSS 186 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 187 scFv aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIK 188 bi- aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG molecule QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTF NSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 189 D2C CDH3-15 VH aa SYPIN CDR1 190 VH aa VIWTGGGTNYASSVKG CDR2 191 VH aa SRGVYDFDGRGAMDY CDR3 192 VL aa KSSQSLLYSSNQKNYLA CDR1 193 VL aa WASTRES CDR2 194 VL aa QQYYSYPYT CDR3 195 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSS 196 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 197 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAED VAVYYCQQYYSYPYTFGQGTKLEIK 198 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT specific NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAED VAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNT AYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGG SGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIG GTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLT VL 199 D2C CDH3-16 VH aa SYPIN CDR1 200 VH aa VIWTGGGTNYNPSLKS CDR2 201 VH aa SRGVYDFDGRGAMDY CDR3 202 VL aa KSSQSLLYSSNQKNYLA CDR1 203 VL aa WASTRES CDR2 204 VL aa QQYYSYPYT CDR3 205 VH aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQVSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSS 206 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 207 scFv aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN YNPSLKSRVTISVDTSKNQVSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIK 208 bi- aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN specific YNPSLKSRVTISVDTSKNQVSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG molecule QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTF NSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 209 D2C CDH3-17 VH aa SYPIN CDR1 210 VH aa VIWTGGGTNYASSVKG CDR2 211 VH aa SRGVYDFDGRGAMDY CDR3 212 VL aa KSSQSLLYSSNQKNYLA CDR1 213 VL aa WASTRES CDR2 214 VL aa QQYYSYPYT CDR3 215 VH aa EVQLLESGGGLVPPGGSLRLSCAVSGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSS 216 VL aa DIVMTQSPDSLAVSVGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 217 scFv aa EVQLLESGGGLVPPGGSLRLSCAVSGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSVGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIK 218 bi- aa EVQLLESGGGLVPPGGSLRLSCAVSGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT specific NYASSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSVGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 219 D2C CDH3-18 VH aa SYPIN CDR1 220 VH aa VIWTGGGTNYASSVKG CDR2 221 VH aa SRGAYDFDGRGAMDY CDR3 222 VL aa KSSQSLLYSSNQKNYLA CDR1 223 VL aa WASTRES CDR2 224 VL aa QQYYSYPYT CDR3 225 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGAYDFDGRGAMDY WGQGTLVTVSS 226 VL aa DIVMTQSPDSLAVSLGEKATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 227 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGAYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGEKATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIK 228 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVGVIWTGGGT specific NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGAYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGEKATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 229 D2C CDH3-19 VH aa SYPIN CDR1 230 VH aa VIWTGGGTNYASSVKG CDR2 231 VH aa SRGVYDFDGRGAMDY CDR3 232 VL aa KSSQSLLYSSNQKNYLA CDR1 233 VL aa WASTRES CDR2 234 VL aa QQYYSYPYT CDR3 235 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWLSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSS 236 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 237 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWLSVIWTGGGT NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAED VAVYYCQQYYSYPYTFGQGTKLEIK 238 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWLSVIWTGGGT specific NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAED VAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNT AYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGG SGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIG GTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLT VL 239 D2C CDH3-20 VH aa SYPIN CDR1 240 VH aa VIWTGGGTNYADSVKG CDR2 241 VH aa RGVYDFDGRGAMDY CDR3 242 VL aa KSSQSLLYSSNQKNYLA CDR1 243 VL aa WASTRES CDR2 244 VL aa QQYYSYPYT CDR3 245 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT NYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGVYDFDGRGAMDY WGQGTLVTVSS 246 VL aa DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYLAWYQQKPGQPPKLLIYWA STRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK 247 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT NYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIK 248 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPINWVRQAPGKGLEWVSVIWTGGGT specific NYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGVYDFDGRGAMDY molecule WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 249 D2C CDH3-21 VH aa SYPIN CDR1 250 VH aa VIWTGGGTNYNSALKS CDR2 251 VH aa SRGVYDFDGRGAMDY CDR3 252 VL aa KSSQSLLYSSNQKNYLA CDR1 253 VL aa WASTRES CDR2 254 VL aa QQYYSYPYT CDR3 255 VH aa EVQLLEESGPGLVTPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY WGQGTTVTVSS 256 VL aa ELVMTQSPSSLAVSVGEKVTMSCKSSQSLLYSSNQKNYLAWYQQKPGQSPKLLIYW ASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPYTFGGGTKLEIK 257 scFv aa EVQLLEESGPGLVTPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIK 258 bi- aa EVQLLEESGPGLVTPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT specific NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY molecule WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSC AASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDS KNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSG GGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPR GLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGG TKLTVLHHHHHH 259 D2C CDH3-22 VH aa SYPIN CDR1 260 VH aa VIWTGGGTNYNSALKS CDR2 261 VH aa SRGVYDFDGRGAMDY CDR3 262 VL aa KSSQSLLYSSNQKNYLA CDR1 263 VL aa WASTRES CDR2 264 VL aa QQYYSYPYT CDR3 265 VH aa EVQLLEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY WGQGTTVTVSS 266 VL aa ELVMTQSPSSLAVSVGEKVTMSCKSSQSLLYSSNQKNYLAWYQQKPGQSPKLLIYW ASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPYTFGGGTKLEIK EVQLLEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY 267 scFv aa WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIK 268 bi- aa EVQLLEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT specific NYNSALKSRLSITKDNSKSQVFLKMTSLQTDDTARYYCAKSRGVYDFDGRGAMDY molecule WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSC AASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDS KNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSG GGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPR GLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGG TKLTVLHHHHHH 269 D2C CDH3-23 VH aa SYPIN CDR1 270 VH aa VIWTGGGTNYDSALKS CDR2 271 VH aa SRGAYDFDGRGAMDY CDR3 272 VL aa KSSQSLLYSSNQKNYLA CDR1 273 VL aa WASTRES CDR2 274 VL aa QQYYSYPYT CDR3 275 VH aa EVQLVEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYDSALKSRLTISKDNSKSQVFLKMNSLQTDDTARYYCARSRGAYDFDGRGAMDY WGQGTTVTVSS 276 VL aa ELVMTQSPSSLAVSVGEKVTMSCKSSQSLLYSSNQKNYLAWYQQKPGQSPKLLIYW ASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPYTFGGGTKLEIK 277 scFv aa EVQLVEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT NYDSALKSRLTISKDNSKSQVFLKMNSLQTDDTARYYCARSRGAYDFDGRGAMDY WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIK 278 bi- aa EVQLVEESGPGLVAPSQSLSITCTVSGFSLTSYPINWVRQPPGKGLEWLGVIWTGGGT specific NYDSALKSRLTISKDNSKSQVFLKMNSLQTDDTARYYCARSRGAYDFDGRGAMDY molecule WGQGTTVTVSSGGGGSGGGGSGGGGSELVMTQSPSSLAVSVGEKVTMSCKSSQSLL YSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAE DLAVYYCQQYYSYPYTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSC AASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDS KNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSG GGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPR GLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGG TKLTVLHHHHHH 279 D3A CDH3-24 VH aa SYWMH CDR1 280 VH aa VIDTSDSYTIYNQKFQG CDR2 281 VH aa SGPGYFDV CDR3 282 VL aa RASGNIHNYLA CDR1 283 VL aa NAKTLAD CDR2 284 VL aa QHFWSTPYT CDR3 285 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFQGRVTMTRDTSTSTAYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSS 286 VL aa DIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWYQQKPGKAPKLLIYNAKTLADG VPSRFSGSGSGTEFTLKISSLQPEDFATYYCQHFWSTPYTFGQGTKLEIK 287 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFQGRVTMTRDTSTSTAYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAW YQQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLKISSLQPEDFATYYCQHFWS TPYTFGQGTKLEIK 288 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS specific DSYTIYNQKFQGRVTMTRDTSTSTAYMELSSLRSEDTAVYYCARSGPGYFDVWGQG molecule TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAW YQQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLKISSLQPEDFATYYCQHFWS TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 289 D3A CDH3-25 VH aa SYWMH CDR1 290 VH aa VIDTSDSYTIYNQKFKG CDR2 291 VH aa SGPGYFDV CDR3 292 VL aa RASENIYSYLA CDR1 293 VL aa NAKTLAE CDR2 294 VL aa QHHYGTPYT CDR3 295 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSS 296 VL aa DIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQKPGKAPKLLIYNAKTLAEGV PSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYGTPYTFGQGTKLEIK 297 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIK 298 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS specific DSYTIYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG molecule TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 299 D3A CDH3-26 VH aa SYWMH CDR1 300 VH aa VIDTSDSYTIYNQKFQG CDR2 301 VH aa SGPGYFDV CDR3 302 VL aa RASENIYSYLA CDR1 303 VL aa NAKTLAE CDR2 304 VL aa QHHYGTPYT CDR3 305 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSS 306 VL aa DIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQKPGKAPKLLVYNAKTLAEG VPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYGTPYTFGQGTKLEIK 307 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLVYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHY GTPYTFGQGTKLEIK 308 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS specific DSYTIYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG molecule TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLVYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHY GTPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNW VRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTED TAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPAR FSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 309 D3A CDH3-27 VH aa SYWMH CDR1 310 VH aa VIDTSDSYTIYAQKFQG CDR2 311 VH aa SGPGYFDV CDR3 312 VL aa RASENIYSYLA CDR1 313 VL aa NAKTLAE CDR2 314 VL aa QHHYGTPYT CDR3 315 VH aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSS 316 VL aa DIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQKPGKAPKLLIYNAKTLAEGV PSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYGTPYTFGQGTKLEIK 317 scFv aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS DSYTIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIK 318 bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS specific DSYTIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG molecule TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 319 D3A CDH3-28 VH aa SYWMH CDR1 320 VH aa VIDTSDSYTIYNQKVKG CDR2 321 VH aa SGPGYFDV CDR3 322 VL aa RASGNIHNYLA CDR1 323 VL aa NAKTLAD CDR2 324 VL aa QHSWSTPYT CDR3 325 VH aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT MVTVSS 326 VL aa DIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWYQQKQGKAPKLLIYNAKTLADG VPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWSTPYTFGQGTKLEIK 327 scFv aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWY QQKQGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWST PYTFGQGTKLEIK 328 bi- aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS specific YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT molecule MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWY QQKQGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWST PYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 329 D3A CDH3-29 VH aa SYWMH CDR1 330 VH aa VIDTSDSYTIYNQKVKG CDR2 331 VH aa SGPGYFDV CDR3 332 VL aa RASGNIHNYLA CDR1 333 VL aa NAKTLAD CDR2 334 VL aa QHSWSTPYT CDR3 335 VH aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT MVTVSS 336 VL aa DIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWYQQKPGKAPKLLIYNAKTLADG VPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWSTPYTFGQGTKLEIK 337 scFv aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWY QQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWST PYTFGQGTKLEIK 338 bi- aa EVQLLESGGGLVRPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWIGVIDTSDS specific YTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCARSGPGYFDVWGQGT molecule MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAWY QQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHSWST PYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 339 D3A CDH3-30 VH aa SYWMH CDR1 340 VH aa VIDTSDSYTIYNQKVKG CDR2 341 VH aa SGPGYFDV CDR3 342 VL aa RASENIYSYLA CDR1 343 VL aa NAKTLAE CDR2 344 VL aa QHHYGTPYT CDR3 345 VH aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWMGVIDTSD SYTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAGDTAVYYCARSGPGYFDVWGQGT MVTVSS 346 VL aa DIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQKPGKAPKLLIYNAKTLAEGV PSRFSGSGSGTEFTLTISSLQPEDFGTYYCQHHYGTPYTFGQGTKLEIK 347 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWMGVIDTSD SYTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAGDTAVYYCARSGPGYFDVWGQGT MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWY QQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFGTYYCQHHYGT PYTFGQGTKLEIK 348 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWMGVIDTSD specific SYTIYNQKVKGRFTISRDNSKNTVYLQMNSLRAGDTAVYYCARSGPGYFDVWGQGT molecule MVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWY QQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFGTYYCQHHYGT PYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 349 D3A CDH3-31 VH aa SYWMH CDR1 350 VH aa VIDTSDSYTIYNQKVKG CDR2 351 VH aa SGPGYFDV CDR3 352 VL aa RASENIYSYLA CDR1 353 VL aa NAKTLAE CDR2 354 VL aa QHHYGTPYT CDR3 355 VH aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWVGVIDTSDS YTIYNQKVKGRFTISRDTSKNTVYLQLNSLRAEDTAVYYCAKSGPGYFDVWGQGTM VTVSS 356 VL aa DIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQKPGKAPKLLIYNAKTLAEGV PSRFSGSGSGTEFTLTISSLQPEDFASYYCQHHYGTPYTFGQGTKLEIK 357 scFv aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWVGVIDTSDS YTIYNQKVKGRFTISRDTSKNTVYLQLNSLRAEDTAVYYCAKSGPGYFDVWGQGTM VTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQ KPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFASYYCQHHYGTPYT FGQGTKLEIK 358 bi- aa EVQLLESGGGLVQPGGSLRLSCAASGYTFSSYWMHWVRQAPGKGLEWVGVIDTSDS specific YTIYNQKVKGRFTISRDTSKNTVYLQLNSLRAEDTAVYYCAKSGPGYFDVWGQGTM molecule VTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAWYQQ KPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFASYYCQHHYGTPYT FGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA PGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT VSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 359 D3A CDH3-32 VH aa SYWMH CDR1 360 VH aa VIDTSDSYTIYNQKFKG CDR2 361 VH aa SGPGYFDV CDR3 362 VL aa RASENIYSYLA CDR1 363 VL aa NAKTLAE CDR2 364 VL aa QHHYGTPYT CDR3 365 VH aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSSVYFCARSGPGYFDVWGQGTT VTVSS 366 VL aa ELQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLAEG VPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGTPYTFGGGTKLEIK 367 scFv aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSSVYFCARSGPGYFDVWGQGTT VTVSSGGGGSGGGGSGGGGSELQMTQSPASLSASVGETVTITCRASENIYSYLAWYQ QKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGT PYTFGGGTKLEIK 368 bi- aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD specific SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSEDSSVYFCARSGPGYFDVWGQGTT molecule VTVSSGGGGSGGGGSGGGGSELQMTQSPASLSASVGETVTITCRASENIYSYLAWYQ QKQGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGT PYTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVT QEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPA RFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 369 D3A CDH3-33 VH aa SYWMH CDR1 370 VH aa VIDTSDSYTIYNQKFKG CDR2 371 VH aa SGPGYFDV CDR3 372 VL aa RASGNIHNYLA CDR1 373 VL aa NAKTLAD CDR2 374 VL aa QHFWSTPYT CDR3 375 VH aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSGDSSVYFCARSGPGYFDVWGQGTT VTVSS 376 VL aa ELVMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAKTLAD GVPSRFSGSGSGTQYSLKINSLQPEDFGTYYCQHFWSTPYTFGGGTKLEIK 377 scFv aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSGDSSVYFCARSGPGYFDVWGQGTT VTVSSGGGGSGGGGSGGGGSELVMTQSPASLSASVGETVTITCRASGNIHNYLAWYQ QKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPEDFGTYYCQHFWST PYTFGGGTKLEIK 378 bi- aa EVQLVEQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGVIDTSD specific SYTIYNQKFKGKATLTVDTSSSTAYMQLSSLTSGDSSVYFCARSGPGYFDVWGQGTT molecule VTVSSGGGGSGGGGSGGGGSELVMTQSPASLSASVGETVTITCRASGNIHNYLAWYQ QKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPEDFGTYYCQHFWST PYTFGGGTKLEIKRTSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVT QEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPA RFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 379 D2C CDH3-13 aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT xI2C - NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY HALB WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL PGGGGSDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFA KTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHK DDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKA AFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARL SQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYE YARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQ NCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRM PCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFN AETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGKKLVAASQAALGL 380 D2C CDH3-13 aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT xI2C - NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY HALB- WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY variant-1 SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL PGGGGSDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFA KTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHK DDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKA AFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARL SQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYE YARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQ NCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRM PCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFN AGTFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAAMDDFAAFVEKCC KADDKETCFAEEGKKLVAASQAALGL 381 D2C CDH3-13 aa QRFVTGHFGGLYPANGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - LY- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-CH VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFCTGHFGGLHPCNGP 382 D2C CDH3-13 aa QRFVTGHFGGLHPANGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - LH- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-CH VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFCTGHFGGLHPCNGP 383 D2C CDH3-13 aa QRFVTGHFGGLHPANGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - LH- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-LH VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFVTGHFGGLHPANGP 384 D2C CDH3-13 aa QRFVTGHFGGLYPANGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - LY- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-LH VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFVTGHFGGLHPANGP 385 D2C CDH3-13 aa QRFCTGHFGGLHPCNGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - CH- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-LH VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNVVVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFVTGHFGGLHPANGP 386 D2C CDH3-13 aa QRFCTGHFGGLHPCNGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - CH- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-LY VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFVTGHFGGLYPANGP 387 D2C CDH3-13 aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT xI2C - 156 NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL GGGGSGGGSRDWDFDVFGGGTPVGGP 388 D2C CDH3-13 aa QRFVTGHFGGLYPANGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - LY- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA FcB-CH- VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS 156 PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFCTGHFGGLHPCNGGGGGSGGGSRD WDFDVFGGGTPVGGP 389 D2C CDH3-13 aa QRFCTGHFGGLHPCNGGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINW xI2C - CH- VRQAPGKGLEWVGVIWTGGGTNYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTA 156 FcB-LY- VYYCAKSRGVYDFDGRGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQS PDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWASTRESGV PDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVLGGGGSQRFVTGHFGGLYPANGGGGGSGGGSRD WDFDVFGGGTPVGGP 390 Human human aa HTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVF epitope cluster D3C 391 Macaque cyno- aa HTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVF epitope molgus cluster D3C 392 linker 1 artificial aa GGGG 393 linker 2 artificial aa GGGGS 394 linker 3 artificial aa GGGGQ 395 linker 4 artificial aa SGGGGS 396 linker 5 artificial aa PGGGGS 397 linker 6 artificial aa PGGDGS 398 linker 7 artificial aa GGGGSGGGS 399 linker 8 artificial aa GGGGSGGGGS 400 linker 9 artificial aa GGGGSGGGGSGGGGS 401 linker 10 artificial aa GGGGSGGGGSGGGGSGGGGS (G4S)4 402 linker 11 artificial aa GGGGSGGGGSGGGGSGGGGSGGGGS (G4S)5 403 linker 12 artificial aa GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (G4S)6 404 linker 13 artificial aa GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (G4S)7 405 linker 14 artificial aa GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (G4S)8 406 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-1 VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK +c/−g TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 407 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-2 VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK +c/−g/ TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY delGK KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 408 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-3 VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE −c/+g KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 409 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-4 VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE −c/+g/ KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN delGK YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 410 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-5 VDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE −c/−g KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 411 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-6 VDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE −c/−g/ KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN delGK YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 412 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-7 VDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK +c/+g TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 413 Fc mono- artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY mer-8 VDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK +c/+g/ TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY delGK KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 414 scFc-1 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK 415 scFc-2 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGG GSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSP 416 scFc-3 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 417 scFc-4 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSP 418 scFc-5 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVV SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 419 scFc-6 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSP 420 scFc-7 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK 421 scFc-8 artificial aa DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYNSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGG GSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYNSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSP 422 D2C CDH3-11 Bi- aa EVQLLESGGGLVQPGGSLRLSCAVSGFTLSSYPINWVRQAPGKGLEWVSVIWTGGGT xI2C -scFc specific NYASSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY HLE WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSVGERVTINCKSSQSLLY molecule SSNQKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 423 D2C CDH3-12 Bi- aa QVQLQESGPGLVKPSETLSLTCTVSGVSITSYPINWIRQPPGKGLEWIGVIWTGGGTN xF12q  specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG -scFc HLE QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPASLAVSLGERATINCKSSQSLLYSSN molecule QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTF NSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 424 D2C CDH3-12 Bi- aa QVQLQESGPGLVKPSETLSLTCTVSGVSITSYPINWIRQPPGKGLEWIGVIWTGGGTN xI2C -scFc specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG HLE QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPASLAVSLGERATINCKSSQSLLYSSN molecule QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 425 D2C CDH3-13 Bi- aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGT xI2C -scFc specific NYASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDY HLE WGQGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLY molecule SSNQKNYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGT KFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 426 D2C CDH3-14 Bi- aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN xF12q  specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG -scFc HLE QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN molecule QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTF NSYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 427 D2C CDH3-14 Bi- aa QVQLQESGPGLVKPSETLSLTCTVSGGSITSYPINWIRQPPGKGLEWIGVIWTGGGTN xI2C -scFc specific YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSRGVYDFDGRGAMDYWG HLE QGTLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSN molecule QKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAV YYCQQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGG GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 428 D3A CDH3-24 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xF12q specific DSYTIYNQKFQGRVTMTRDTSTSTAYMELSSLRSEDTAVYYCARSGPGYFDVWGQG -scFc HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAW molecule YQQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLKISSLQPEDFATYYCQHFWS TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG GGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 429 D3A CDH3-24 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xI2C -scFc specific DSYTIYNQKFQGRVTMTRDTSTSTAYMELSSLRSEDTAVYYCARSGPGYFDVWGQG HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASGNIHNYLAW molecule YQQKPGKAPKLLIYNAKTLADGVPSRFSGSGSGTEFTLKISSLQPEDFATYYCQHFWS TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNW VRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTE DTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPAR FSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 430 D3A CDH3-25 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xF12q specific DSYTIYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG -scFc HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG GGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 431 D3A CDH3-25 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xI2C -scFc specific DSYTIYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNW VRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTE DTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPAR FSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 432 D3A CDH3-26 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xF12q specific DSYTIYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG -scFc HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLVYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHY GTPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNW VRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTED TAVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPAR FSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 433 D3A CDH3-26 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xI2C -scFc specific DSYTIYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLVYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHY GTPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVT QEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPA RFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG SGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK 434 D3A CDH3-27 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xF12q  specific DSYTIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG -scFc HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWV RQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDT AVYYCVRHGNFGNSYVSWWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQE PSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFS GSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG GGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK 435 D3A CDH3-27 Bi- aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGVIDTS xI2C -scFc specific DSYTIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSGPGYFDVWGQG HLE TMVTVSSGGGGSGGGGSGGGGSDIQLTQSPSFLSASVGDRVTITCRASENIYSYLAW molecule YQQKPGKAPKLLIYNAKTLAEGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQHHYG TPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNW VRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTE DTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPAR FSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 436 Hexa-his artificial aa HHHHHH 437 P156 artificial aa RDWDFDVFGGGTPVGG 438 linear artificial aa QRFVTGHFGGLXPANG FcRn BP 439 linear artificial aa QRFVTGHFGGLYPANG FcRn BP-Y 440 linear artificial aa QRFVTGHFGGLHPANG FcRn BP-H 441 core FcRn artificial aa TGHFGGLHP BP-H 442 cyclic artificial aa QRFCTGHFGGLHPCNG FcRn BP-H 443 HALB human aa DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECC QAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPK AEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKP LLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRH PDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELF EQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAED YLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTF HADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKE TCFAEEGKKLVAASQAALGL 444 HALB human aa DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVAD variant 1 ESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECC QAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPK AEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKP LLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRH PDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELF EQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAED YLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAGTFT FHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAAMDDFAAFVEKCCKADDK ETCFAEEGKKLVAASQAALGL 445 CDR-L1 of artificial aa GSSTGAVTSGYYPN F6A 446 CDR-L2 of artificial aa GTKFLAP F6A 447 CDR-L3 of artificial aa ALWYSNRWV F6A 448 CDR-H1 of artificial aa IYAMN F6A 449 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKS F6A 450 CDR-H3 of artificial aa HGNFGNSYVSFFAY F6A 451 VH of F6A artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFF AYWGQGTLVTVSS 452 VL of F6A artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 453 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYN F6A NYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFF AYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCALWYSNRWVFGGGTKLTVL 454 CDR-L1 of artificial aa GSSTGAVTSGYYPN H2C 455 CDR-L2 of artificial aa GTKFLAP H2C 456 CDR-L3 of artificial aa ALWYSNRWV H2C 457 CDR-H1 of artificial aa KYAMN H2C 458 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKD H2C 459 CDR-H3 of artificial aa HGNFGNSYISYWAY H2C 460 VH of H2C artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSS 461 VL of H2C artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 462 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY H2C NNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 463 CDR-L1 of artificial aa GSSTGAVTSGYYPN H1E 464 CDR-L2 of artificial aa GTKFLAP H1E 465 CDR-L3 of artificial aa ALWYSNRWV H1E 466 CDR-H1 of artificial aa SYAMN H1E 467 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKG H1E 468 CDR-H3 of artificial aa HGNFGNSYLSFWAY H1E 469 VH of H1E artificial aa EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSF WAYWGQGTLVTVSS 470 VL of H1E artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 471 VH-VL of artificial aa EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYN H1E NYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSF WAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 472 CDR-L1 of artificial aa GSSTGAVTSGYYPN G4H 473 CDR-L2 of artificial aa GTKFLAP G4H 474 CDR-L3 of artificial aa ALWYSNRWV G4H 475 CDR-H1 of artificial aa RYAMN G4H 476 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKG G4H 477 CDR-H3 of artificial aa HGNFGNSYLSYFAY G4H 478 VH of G4H artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLS YFAYWGQGTLVTVSS 479 VL of G4H artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 480 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKY G4H NNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLS YFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSST GAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCALWYSNRWVFGGGTKLTVL 481 CDR-L1 of artificial aa RSSTGAVTSGYYPN A2J 482 CDR-L2 of artificial aa ATDMRPS A2J 483 CDR-L3 of artificial aa ALWYSNRWV A2J 484 CDR-H1 of artificial aa VYAMN A2J 485 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKK A2J 486 CDR-H3 of artificial aa HGNFGNSYLSWWAY A2J 487 VH of A2J artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLS WWAYWGQGTLVTVSS 488 VL of A2J artificial aa QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRP SGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 489 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKY A2J NNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLS WWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCRSST GAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQP EDEAEYYCALWYSNRWVFGGGTKLTVL 490 CDR-L1 of artificial aa GSSTGAVTSGYYPN E1L 491 CDR-L2 of artificial aa GTKFLAP E1L 492 CDR-L3 of artificial aa ALWYSNRWV E1L 493 CDR-H1 of artificial aa KYAMN E1L 494 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKS E1L 495 CDR-H3 of artificial aa HGNFGNSYTSYYAY E1L 496 VH of E1L artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSY YAYWGQGTLVTVSS 497 VL of E1L artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 498 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY E1L NNYATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSY YAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 499 CDR-L1 of artificial aa RSSTGAVTSGYYPN E2M 500 CDR-L2 of artificial aa ATDMRPS E2M 501 CDR-L3 of artificial aa ALWYSNRWV E2M 502 CDR-H1 of artificial aa GYAMN E2M 503 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKE E2M 504 CDR-H3 of artificial aa HRNFGNSYLSWFAY E2M 505 VH of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKY E2M NNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLS WFAYWGQGTLVTVSS 506 VL of E2M artificial aa QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRP SGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 507 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKY E2M NNYATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLS WFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCRSST GAVTSGYYPNWVQQKPGQAPRGLIGATDMRPSGTPARFSGSLLGGKAALTLSGVQP EDEAEYYCALWYSNRWVFGGGTKLTVL 508 CDR-L1 of artificial aa GSSTGAVTSGYYPN F7O 509 CDR-L2 of artificial aa GTKFLAP F7O 510 CDR-L3 of artificial aa ALWYSNRWV F7O 511 CDR-H1 of artificial aa VYAMN F7O 512 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKK F7O 513 CDR-H3 of artificial aa HGNFGNSYISWWAY F7O 514 VH of F7O artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYIS WWAYWGQGTLVTVSS 515 VL of F7O artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL 516 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKY F7O NNYATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYIS WWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSS TGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP EDEAEYYCALWYSNRWVFGGGTKLTVL 517 CDR-L1 of artificial aa GSSTGAVTSGNYPN F12Q 518 CDR-L2 of artificial aa GTKFLAP F12Q 519 CDR-L3 of artificial aa VLWYSNRWV F12Q 520 CDR-H1 of artificial aa SYAMN F12Q 521 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKG F12Q 522 CDR-H3 of artificial aa HGNFGNSYVSWWAY F12Q 523 VH of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKY F12Q NNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVS WWAYWGQGTLVTVSS 524 VL of artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA F12Q PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 525 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKY F12Q NNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVS WWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSS TGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP EDEAEYYCVLWYSNRWVFGGGTKLTVL 526 CDR-L1 of artificial aa GSSTGAVTSGNYPN I2C 527 CDR-L2 of artificial aa GTKFLAP I2C 528 CDR-L3 of artificial aa VLWYSNRWV I2C 529 CDR-H1 of artificial aa KYAMN I2C 530 CDR-H2 of artificial aa RIRSKYNNYATYYADSVKD I2C 531 CDR-H3 of artificial aa HGNFGNSYISYWAY I2C 532 VH of I2C artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSS 533 VL of I2C artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 534 VH-VL of artificial aa EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY I2C NNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 535 VH of artificial aa EVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYN F12q NYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDTAVYYCVRHGNFGNSYVSW WAYWGQGTLVTVSS 536 VL of F12q artificial aa QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 537 VH-VL of artificial aa EVQLVESGGGLVQPGGSLRLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYN F12q NYATYYADSVKGRFTISRDDSKNTAYLQMNSLKTEDTAVYYCVRHGNFGNSYVSW WAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL