US20220127354A1

US20220127354A1 - Antibodies targeting cdh19 for melanoma

Info

Publication number: US20220127354A1
Application number: US17/326,717
Authority: US
Inventors: Shouhua Xiao; Zheng Pan; Dineli Wickramasinghe; M. Shawn Jeffries; Chadwick Terence King; Brian Mingtung Chan
Original assignee: Amgen Inc
Current assignee: Amgen Inc
Priority date: 2013-01-25
Filing date: 2021-05-21
Publication date: 2022-04-28
Also published as: US9920121B2; WO2014114801A1; US20150322151A1; ES2728936T3; EP2948478B1; EP2948478A1; US11053311B2; US20180208654A1

Abstract

The present disclosure provides a human antibody or antigen binding fragment thereof or an antibody construct comprising a human binding domain or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell. The disclosure relates to a nucleic acid sequence encoding the antibody or antigen binding fragment thereof contained in the antibody construct, a vector comprising the nucleic acid sequence and a host cell transformed or transfected with the vector. Furthermore, the disclosure relates to a process for the production of the antibody construct of the disclosure, a medical use or a method of treatment using the antibody construct and a kit comprising the antibody or antigen binding fragment thereof or the antibody construct.

Description

RELATED APPLICATIONS

This application is related to a U.S. provisional application entitled “Antibody constructs for CDH19 and CD3,” filed on Mar. 15, 2013, the same day as the present application is filed. This related application is incorporated in its entirety by reference.

FIELD OF THE INVENTION

The present invention relates to compositions of antigen binding proteins including antibodies capable of binding to human CDH19 on the surface of a target cell, as well as related methods. Moreover, the invention provides a nucleic acid sequence encoding the antibody construct, a vector comprising the nucleic acid sequence and a host cell transformed or transfected with the nucleic acid sequence or a vector comprising the nucleic acid sequence. Furthermore, the invention provides a process for the production of the antibody of the invention, a method of treatment using the antibody and a kit comprising the antibody.

BACKGROUND OF THE INVENTION

Melanoma is a skin cancer that is caused by the oncogenic transformation of melanocytes, which are pigment producing skin cells. As of 2009, Melanoma had a prevalence of more than 870,000 cases in the US alone (US National Institutes of Health). Each year, over 75,000 new cases of melanoma are diagnosed in the US, and approximately 25% of patients have advanced disease at the time of diagnosis. Despite the fact that cases of primary melanoma can be cured by surgery if they are detected early enough, melanoma is the leading cause of death from skin disease in the US, responsible for about 10,000 deaths per year in the US. Once the disease has spread and became metastatic, the prognosis is poor, with a 5 year relative survival of 15%.
There are four basic types of melanomas. Three types are found in the top layers of the skin and the fourth one is invasive and has penetrated deeper into the skin and may have spread to other areas of the body.
Superficial spreading melanoma is the most common type of melanoma which accounts for about 70% of all cases. It grows along the top layer of the skin for a fairly long time before penetrating more deeply. It first appears as a flat or slightly raised discolored patch that has irregular borders and may be somewhat asymmetrical in form. The color varies, and you may see areas of tan, brown, black, red, blue or white. This type of melanoma can occur in a previously benign mole and is found most often in young people.
Lentigo maligna is similar to the superficial spreading type, as it also remains close to the skin surface for quite a while, and usually appears as a flat or mildly elevated mottled tan, brown or dark brown discoloration. It is found most often in the elderly. When this cancer becomes invasive, it is referred to as lentigo maligna melanoma.
Acral lentiginous melanoma also spreads superficially before penetrating more deeply. It is quite different from the others, though, as it usually appears as a black or brown discoloration under the nails or on the soles of the feet or palms of the hands. This type of melanoma is sometimes found on dark-skinned people, and can often advance more quickly than superficial spreading melanoma and lentigo maligna.
Nodular melanoma is usually invasive at the time it is first diagnosed. The malignancy is recognized when it becomes a bump. It is usually black, but occasionally is blue, gray, white, brown, tan, red or skin tone. This is the most aggressive of the melanomas, and is found in 10 to 15 percent of cases.
Common treatments for metastatic melanoma include chemotherapy, targeted therapies for eligible patients (e.g. BRAF inhibitor treatment for patients with BRAF mutations) and immunotherapy. Metastatic melanoma is a tumor type where immunotherapy has been demonstrated to not only slow disease progression, but to lead to cures in late stage patients. Interleukin-2 was approved for the use in metastatic melanoma in 1998, and in 2011 an antibody targeting CTLA4, a member of a new generation of immune checkpoint inhibitors, gained approval by the FDA.
CDH19 is a type II cadherin transmembrane protein of unknown function. The human gene was cloned in 2000 based on its sequence similarity to CDH7 (Kools, P. et al. Genomics. 2000). Expressed Sequence Tags (ESTs) for CDH19 were isolated from melanocyte cDNA libraries, indicating that expression of CDH19 may be limited to cells of neural crest origin (Kools, P. et al. Genomics. 2000). In support of this notion, rat CDH19 was found to be expressed primarily in nerve ganglia and in Schwann cells during rat embryonic development (Takahashi, M. and Osumi, O. Devl Dynamics. 2005).
Diagnostic antibodies detecting CDH19 in Western Blot, immunohistochemitstry or flow cytometry are known in the art and commercially available. Those antibodies comprise poly- and monoclonal antibodies generated in animal hosts.

SUMMARY OF THE INVENTION

The present invention provides an isolated human antibody or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell. In a preferred embodiment the antibody or antigen binding fragment thereof comprises a monoclonal antibody or a fragment thereof.
In one embodiment the human antibody or antigen binding fragment thereof of the invention comprises a human binding domain or antigen binding fragment thereof comprising a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:

(a) CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 222, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 252, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926, and CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 904, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926;
(b) CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 126, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 300, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 306, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 312, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 928, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 929, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 942, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 943, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 937, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 919, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 936, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 933, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 917, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 934, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 930, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 931, and
CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 932;
(c) CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 96, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 102, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID NO: 156, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 912, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 913, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 910, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 911, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 914, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, and
CDR-H1 as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID NO: 920, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324;
(d) CDR-H1 as depicted in SEQ ID NO: 4, CDR-H2 as depicted in SEQ ID NO: 5, CDR-H3 as depicted in SEQ ID NO: 6, CDR-L1 as depicted in SEQ ID NO: 172, CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3 as depicted in SEQ ID NO: 174, CDR-H1 as depicted in SEQ ID NO: 10, CDR-H2 as depicted in SEQ ID NO: 11, CDR-H3 as depicted in SEQ ID NO: 12, CDR-L1 as depicted in SEQ ID NO: 178, CDR-L2 as depicted in SEQ ID NO: 179 and CDR-L3 as depicted in SEQ ID NO: 180, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 198, CDR-H1 as depicted in SEQ ID NO: 34, CDR-H2 as depicted in SEQ ID NO: 35, CDR-H3 as depicted in SEQ ID NO: 36, CDR-L1 as depicted in SEQ ID NO: 202, CDR-L2 as depicted in SEQ ID NO: 203 and CDR-L3 as depicted in SEQ ID NO: 204, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 214, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 59, CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 64, CDR-H2 as depicted in SEQ ID NO: 65, CDR-H3 as depicted in SEQ ID NO: 66, CDR-L1 as depicted in SEQ ID NO: 232, CDR-L2 as depicted in SEQ ID NO: 233 and CDR-L3 as depicted in SEQ ID NO: 234, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 71, CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 328, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 902, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 903, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 925, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID NO: 908, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID NO: 906, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 921, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 940, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 941, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, and CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330; and
(e) CDR-H1 as depicted in SEQ ID NO: 76, CDR-H2 as depicted in SEQ ID NO: 77, CDR-H3 as depicted in SEQ ID NO: 78, CDR-L1 as depicted in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245 and CDR-L3 as depicted in SEQ ID NO: 246, CDR-H1 as depicted in SEQ ID NO: 88, CDR-H2 as depicted in SEQ ID NO: 89, CDR-H3 as depicted in SEQ ID NO: 90, CDR-L1 as depicted in SEQ ID NO: 256, CDR-L2 as depicted in SEQ ID NO: 257 and CDR-L3 as depicted in SEQ ID NO: 258, CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276, CDR-H1 as depicted in SEQ ID NO: 112, CDR-H2 as depicted in SEQ ID NO: 113, CDR-H3 as depicted in SEQ ID NO: 114, CDR-L1 as depicted in SEQ ID NO: 280, CDR-L2 as depicted in SEQ ID NO: 281 and CDR-L3 as depicted in SEQ ID NO: 282, and
CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276.

In a further embodiment of the human antibody or antigen binding fragment thereof of the invention the human binding domain or antigen binding fragment thereof comprises a VH region selected from the group consisting of VH regions

(a) as depicted in SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, and SEQ ID NO: 495;
(b) as depicted in SEQ ID NO: 342, SEQ ID NO: 366, SEQ ID NO: 370, SEQ ID NO: 344, SEQ ID NO: 372, SEQ ID NO: 368, SEQ ID NO: 496, SEQ ID NO: 497, SEQ ID NO: 498, SEQ ID NO: 499, SEQ ID NO: 500, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO: 510, SEQ ID NO: 511, SEQ ID NO: 512, SEQ ID NO: 519, SEQ ID NO: 520, SEQ ID NO: 521, SEQ ID NO: 522, SEQ ID NO: 523, SEQ ID NO: 524, SEQ ID NO: 525, SEQ ID NO: 526, SEQ ID NO: 527, SEQ ID NO: 528, SEQ ID NO: 529, SEQ ID NO: 530, SEQ ID NO: 531, SEQ ID NO: 532, SEQ ID NO: 533, SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 536, SEQ ID NO: 537, and SEQ ID NO: 538;
(c) as depicted in SEQ ID NO: 338, SEQ ID NO: 354, SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484, SEQ ID NO: 501, SEQ ID NO: 502, SEQ ID NO: 503, SEQ ID NO: 504, SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 517, and SEQ ID NO: 518;
(d) as depicted in SEQ ID NO: 352, SEQ ID NO: 360, SEQ ID NO: 388, SEQ ID NO: 386, SEQ ID NO: 340, SEQ ID NO: 346, SEQ ID NO: 374, SEQ ID NO: 348, SEQ ID NO: 390, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466, SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472, SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490, SEQ ID NO: 491, SEQ ID NO: 513, SEQ ID NO: 514, SEQ ID NO: 515, SEQ ID NO: 516, SEQ ID NO: 540, SEQ ID NO: 541, SEQ ID NO: 542, and SEQ ID NO: 543; and
(e) as depicted in SEQ ID NO: 376, SEQ ID NO: 392, SEQ ID NO: 358, SEQ ID NO: 350, and SEQ ID NO: 507.

In another embodiment the human antibody or antigen binding fragment thereof of the invention comprises the human binding domain or antigen binding fragment thereof comprising a VL region selected from the group consisting of VL regions

(a) as depicted in SEQ ID NO: 418, SEQ ID NO: 420, SEQ ID NO: 580, SEQ ID NO: 581, SEQ ID NO: 582, SEQ ID NO: 587, SEQ ID NO: 588, SEQ ID NO: 589, and SEQ ID NO: 590;
(b) as depicted in SEQ ID NO: 398, SEQ ID NO: 422, SEQ ID NO: 426, SEQ ID NO: 400, SEQ ID NO: 428, SEQ ID NO: 424, SEQ ID NO: 591, SEQ ID NO: 592, SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 603, SEQ ID NO: 604, SEQ ID NO: 605, SEQ ID NO: 606, SEQ ID NO: 607, SEQ ID NO: 614, SEQ ID NO: 615, SEQ ID NO: 616, SEQ ID NO: 617, SEQ ID NO: 618, SEQ ID NO: 619, SEQ ID NO: 620, SEQ ID NO: 621, SEQ ID NO: 622, SEQ ID NO: 623, SEQ ID NO: 624, SEQ ID NO: 625, SEQ ID NO: 626, SEQ ID NO: 627, SEQ ID NO: 628, SEQ ID NO: 629, SEQ ID NO: 630, SEQ ID NO: 631, SEQ ID NO: 632, and SEQ ID NO: 633;
(c) as depicted in SEQ ID NO: 394, SEQ ID NO: 410, SEQ ID NO: 434, SEQ ID NO: 412, SEQ ID NO: 571, SEQ ID NO: 572, SEQ ID NO: 573, SEQ ID NO: 574, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 578, SEQ ID NO: 579, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 598, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO: 601, SEQ ID NO: 612, and SEQ ID NO: 613;
(d) as depicted in SEQ ID NO: 408, SEQ ID NO: 416, SEQ ID NO: 444, SEQ ID NO: 442, SEQ ID NO: 396, SEQ ID NO: 402, SEQ ID NO: 430, SEQ ID NO: 404, SEQ ID NO: 446, SEQ ID NO: 558, SEQ ID NO: 559, SEQ ID NO: 560, SEQ ID NO: 561, SEQ ID NO: 562, SEQ ID NO: 563, SEQ ID NO: 564, SEQ ID NO: 565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO: 568, SEQ ID NO: 569, SEQ ID NO: 570, SEQ ID NO: 583, SEQ ID NO: 584, SEQ ID NO: 585, SEQ ID NO: 586, SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, SEQ ID NO: 611, SEQ ID NO: 635, SEQ ID NO: 636, SEQ ID NO: 637, and SEQ ID NO: 638; and
(e) as depicted in SEQ ID NO: 432, SEQ ID NO: 448, SEQ ID NO: 414, SEQ ID NO: 406, and SEQ ID NO: 602.

The invention further provides an embodiment of the human antibody or antigen binding fragment thereof of the invention, wherein the human binding domain or antigen binding fragment thereof comprises a VH region and a VL region selected from the group consisting of:

(1) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 362+418, SEQ ID NOs: 364+420, SEQ ID NOs: 485+580, SEQ ID NOs: 486+581, SEQ ID NOs: 487+582, SEQ ID NOs: 492+587, SEQ ID NOs: 493+588, SEQ ID NOs: 494+589, and SEQ ID NOs: 495+590;
(2) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 342+398, SEQ ID NOs: 366+422, SEQ ID NOs: 370+426, SEQ ID NOs: 344+400, SEQ ID NOs: 372+428, SEQ ID NOs: 368+424, SEQ ID NOs: 496+591, SEQ ID NOs: 497+592, SEQ ID NOs: 498+593, SEQ ID NOs: 499+594, SEQ ID NOs: 500+595, SEQ ID NOs: 508+603, SEQ ID NOs: 509+604, SEQ ID NOs: 510+605, SEQ ID NOs: 511+606, SEQ ID NOs: 512+607, SEQ ID NOs: 519+614, SEQ ID NOs: 520+615, SEQ ID NOs: 521+616, SEQ ID NOs: 522+617, SEQ ID NOs: 523+618, SEQ ID NOs: 524+619, SEQ ID NOs: 525+620, SEQ ID NOs: 526+621, SEQ ID NOs: 527+622, SEQ ID NOs: 528+623, SEQ ID NOs: 529+624, SEQ ID NOs: 530+625, SEQ ID NOs: 531+626, SEQ ID NOs: 532+627, SEQ ID NOs: 533+628, SEQ ID NOs: 534+629, SEQ ID NOs: 535+630, SEQ ID NOs: 536+631, SEQ ID NOs: 537+632, and SEQ ID NOs: 538+633;
(3) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 338+394, SEQ ID NOs: 354+410, SEQ ID NOs: 378+434, SEQ ID NOs: 356+412, SEQ ID NOs: 476+571, SEQ ID NOs: 477+572, SEQ ID NOs: 478+573, SEQ ID NOs: 479+574, SEQ ID NOs: 480+575, SEQ ID NOs: 481+576, SEQ ID NOs: 482+577, SEQ ID NOs: 483+578, SEQ ID NOs: 484+579, SEQ ID NOs: 501+596, SEQ ID NOs: 502+597, SEQ ID NOs: 503+598, SEQ ID NOs: 504+599, SEQ ID NOs: 505+600, SEQ ID NOs: 506+601, SEQ ID NOs: 517+612, and SEQ ID NOs: 518+613;
(4) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 352+408, SEQ ID NOs: 360+416, SEQ ID NOs: 388+444, SEQ ID NOs: 386+442, SEQ ID NOs: 340+396, SEQ ID NOs: 346+402, SEQ ID NOs: 374+430, SEQ ID NOs: 348+404, SEQ ID NOs: 390+446, SEQ ID NOs: 463+558, SEQ ID NOs: 464+559, SEQ ID NOs: 465+560, SEQ ID NOs: 466+561, SEQ ID NOs: 467+562, SEQ ID NOs: 468+563, SEQ ID NOs: 469+564, SEQ ID NOs: 470+565, SEQ ID NOs: 471+566, SEQ ID NOs: 472+567, SEQ ID NOs: 473+568, SEQ ID NOs: 474+569, SEQ ID NOs: 475+570, SEQ ID NOs: 488+583, SEQ ID NOs: 489+584, SEQ ID NOs: 490+585, SEQ ID NOs: 491+586, SEQ ID NOs: 513+608, SEQ ID NOs: 514+609, SEQ ID NOs: 515+610, SEQ ID NOs: 516+611, SEQ ID NOs: 540+635, SEQ ID NOs: 541+636, SEQ ID NOs: 542+637, and SEQ ID NOs: 543+638; and
(5) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 376+432, SEQ ID NOs: 392+448, SEQ ID NOs: 358+414, SEQ ID NOs: 350+406, and SEQ ID NOs: 507+602.

In a further embodiment the human binding domain or antigen binding fragment thereof comprises the groups of heavy and light chains having an amino acid sequence selected from the group consisting of

(1) a heavy and light chain as depicted in SEQ ID NOs: 644+680, SEQ ID NOs: 650+686, SEQ ID NOs: 747+842, SEQ ID NOs: 748+843, SEQ ID NOs: 749+844, SEQ ID NOs: 754+849, SEQ ID NOs: 755+850, SEQ ID NOs: 756+851, and SEQ ID NOs: 757+852;
(2) a heavy and light chain as depicted in SEQ ID NOs: 660+696, SEQ ID NOs: 662+698, SEQ ID NOs: 668+704, SEQ ID NOs: 674+710, SEQ ID NOs: 672+708, SEQ ID NOs: 658+694, SEQ ID NOs: 758+853, SEQ ID NOs: 759+854, SEQ ID NOs: 760+855, SEQ ID NOs: 761+856, SEQ ID NOs: 762+857, SEQ ID NOs: 770+865, SEQ ID NOs: 771+866, SEQ ID NOs: 772+867, SEQ ID NOs: 773+868, SEQ ID NOs: 774+869, SEQ ID NOs: 781+876, SEQ ID NOs: 782+877, SEQ ID NOs: 783+878, SEQ ID NOs: 784+879, SEQ ID NOs: 785+880, SEQ ID NOs: 786+881, SEQ ID NOs: 787+882, SEQ ID NOs: 788+883, SEQ ID NOs: 789+884, SEQ ID NOs: 790+885, SEQ ID NOs: 791+886, SEQ ID NOs: 792+887, SEQ ID NOs: 793+888, SEQ ID NOs: 794+889, SEQ ID NOs: 795+890, SEQ ID NOs: 796+891, SEQ ID NOs: 797+892, SEQ ID NOs: 798+893, SEQ ID NOs: 799+894, and SEQ ID NOs: 800+895;
(3) a heavy and light chain as depicted in SEQ ID NOs: 656+692, SEQ ID NOs: 654+690, SEQ ID NOs: 664+700, SEQ ID NOs: 670+706, SEQ ID NOs: 738+833, SEQ ID NOs: 739+834, SEQ ID NOs: 740+835, SEQ ID NOs: 741+836, SEQ ID NOs: 742+837, SEQ ID NOs: 743+838, SEQ ID NOs: 744+839, SEQ ID NOs: 745+840, SEQ ID NOs: 746+841, SEQ ID NOs: 763+858, SEQ ID NOs: 764+859, SEQ ID NOs: 765+860, SEQ ID NOs: 766+861, SEQ ID NOs: 767+862, SEQ ID NOs: 768+863, SEQ ID NOs: 779+874, and SEQ ID NOs: 780+875;
(4) a heavy and light chain as depicted in SEQ ID NOs: 640+676, SEQ ID NOs: 642+678, SEQ ID NOs: 646+682, SEQ ID NOs: 648+684, SEQ ID NOs: 666+702, SEQ ID NOs: 725+820, SEQ ID NOs: 726+821, SEQ ID NOs: 727+822, SEQ ID NOs: 728+823, SEQ ID NOs: 729+824, SEQ ID NOs: 730+825, SEQ ID NOs: 731+826, SEQ ID NOs: 732+827, SEQ ID NOs: 733+828, SEQ ID NOs: 734+829, SEQ ID NOs: 735+830, SEQ ID NOs: 736+831, SEQ ID NOs: 737+832, SEQ ID NOs: 750+845, SEQ ID NOs: 751+846, SEQ ID NOs: 752+847, SEQ ID NOs: 753+848, SEQ ID NOs: 775+870, SEQ ID NOs: 776+871, SEQ ID NOs: 777+872, SEQ ID NOs: 778+873, SEQ ID NOs: 802+897, SEQ ID NOs: 803+898, SEQ ID NOs: 804+899, and SEQ ID NOs: 805+900; and
(5) a heavy and light chain as depicted in SEQ ID NOs: 652+688, and SEQ ID NOs: 769+864.

In another embodiment the invention is directed to an antibody construct comprising the human antibody or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell as described above that is conjugated to a chemotherapeutic agent.
In one embodiment of the antibody construct of the invention a linker conjugates the chemotherapeutic agent to the human antibody or antigen binding fragment thereof.
In a preferred embodiment of the antibody construct of the invention the linker is a non-cleavable linker.
It is also preferred that the linker in the antibody construct of the invention comprises MCC.
In a further embodiment of the antibody construct of the invention the chemotherapeutic agent is conjugated to one or more lysines contained in the human antibody or antigen binding fragment thereof.
In one embodiment of the antibody construct of the invention the chemotherapeutic agent is DM1.
In a preferred embodiment of the antibody construct of the invention the average number of DM1 molecules per antibody construct is between 1 and 10.
It is also preferred for the antibody construct of the invention that the average number of DM1 molecules per antibody construct is between 3 and 7.
Moreover, it is preferred for the antibody construct of the invention that the average number of DM1 molecules per antibody construct is between 4 and 6.
In a further alternative embodiment of the antibody construct of the invention the average number of DM1 molecules per antibody construct is about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0.
The invention further provides an isolated nucleic acid molecule or sequence encoding a human antibody or antigen binding fragment thereof of the invention.
Furthermore, the invention provides a vector comprising a nucleic acid sequence of the invention. Moreover, the invention provides a host cell transformed or transfected with the nucleic acid sequence of the invention or with a vector comprising the nucleic acid molecule.
In a further embodiment the invention provides a process for the production of a human antibody or an antigen binding fragment thereof of the invention, said process comprising culturing a host cell of the invention under conditions allowing the expression of the human antibody or antigen binding fragment thereof of the invention and recovering the produced antibody or antigen binding fragment thereof from the culture.
In a further embodiment the invention provides a process for the production of an antibody construct comprising a human antibody or an antigen binding fragment thereof of the invention, said process comprising culturing a host cell of the invention under conditions allowing the expression of the human antibody or antigen binding fragment thereof of the invention and recovering the produced antibody or antigen binding fragment thereof from the culture, and conjugating a chemotherapeutic agent to the recovered antibody or antigen binding fragment thereof to produce the antibody conjugate.
Moreover, the invention provides a pharmaceutical composition comprising a human antibody or antigen binding fragment thereof of the invention or an antibody construct of the invention or produced according to the process of the invention in admixture with a pharmaceutically acceptable carrier thereof.
In one embodiment the invention provides the human antibody or antigen binding fragment thereof of the invention, the antibody construct of the invention, or produced according to the process of the invention for use in the prevention, treatment or amelioration of a melanoma disease or metastatic melanoma disease. Preferably, the melanoma disease or metastatic melanoma disease is selected from the group consisting of superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, acral lentiginous melanoma and nodular melanoma.
The invention also provides a method for the treatment or amelioration of a melanoma disease or metastatic melanoma disease, comprising the step of administering to a subject in need thereof the antibody or antigen binding fragment thereof of the invention, the antibody construct of the invention, an antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention produced according to the process of the invention or a pharmaceutical composition of the invention.
In a preferred embodiment method the invention the melanoma disease or metastatic melanoma disease is selected from the group consisting of superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, acral lentiginous melanoma and nodular melanoma.
In a further embodiment, the invention provides a kit comprising an antibody or antigen binding fragment thereof of the invention, an antibody construct of the invention, an antibody or antigen binding fragment thereof of the invention or the antibody construct produced according to the process of the invention, a vector of the invention, and/or a host cell of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts cell viability data of Colo-699 cells that have been treated with fully human anti-CDH19 antibodies and a high concentration of a goat anti-human Fc monovalent Fab conjugated with DM1 (DM1-Fab) at a drug-antibody ratio (DAR) (˜1.3).

FIG. 2 depicts the average cell viability data from a CHL-1 assay plotted against the average cell viability data from the Colo-699 assay.

FIG. 3 shows the relative expression of CDH19 mRNA in metastatic and primary melanoma samples.

FIG. 4 shows the expression of CDH19 protein in human tumor samples by IHC.

FIG. 5 shows the results of the analysis of tumor cell lines by flow cytometry and IHC to identify model systems with CDH19 expression similar to human tumors based on the number of CDH19 receptors present on the cell surface.

FIG. 6 shows in vitro activity of a CDH19 ADC against the model tumor cell lines.

FIG. 7 shows in vitro activity of a CDH19 ADC in model tumor cell lines at varying DAR ratios.

FIG. 8 shows in vivo activity of CDH19 ADCs in a xenograft mouse model as compared to naked CDH19 antibodies.

FIG. 9 shows in vivo activity of CDH19 ADCs in a xenograft mouse model. 4B10-DM1 Moderately Inhibited Tumor Growth at 182 μg/kg DM1 in CHL-1 Xenografts

FIG. 10 shows in vivo activity of CDH19 ADCs in a xenograft mouse model. Increasing the DAR Did Not Increase Tumor Growth Inhibition in CHL-1 Xenografts

FIG. 11 shows in vivo activity of CDH19 ADCs in a xenograft mouse model. Anti-CDH19 ADCs Moderately Inhibited Tumor Growth in COLO699 Xenografts

DETAILED DESCRIPTION OF THE INVENTION

Definitions

It must be noted that as used herein, the singular forms “a”, “an”, and “the”, include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “a reagent” includes one or more of such different reagents and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein.
Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.
The term “and/or” wherever used herein includes the meaning of “and”, “or” and “all or any other combination of the elements connected by said term”.
The term “about” or “approximately” as used herein means within ±20%, preferably within ±15%, more preferably within ±10%, and most preferably within ±5% of a given value or range.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. When used herein the term “comprising” can be substituted with the term “containing” or “including” or sometimes when used herein with the term “having”.
When used herein “consisting of” excludes any element, step, or ingredient not specified in the claim element. When used herein, “consisting essentially of” does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.
In each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms.
The definition of the term “antibody” includes embodiments such as monoclonal, chimeric, single chain, humanized and human antibodies, as well as antibody fragments, like, inter alia, Fab fragments. Antibody fragments or derivatives further comprise F(ab′)₂, Fv, scFv fragments or single domain antibodies such as domain antibodies or nanobodies, single variable domain antibodies or immunoglobulin single variable domain comprising merely one variable domain, which might be VHH, VH or VL, that specifically bind an antigen or epitope independently of other V regions or domains; see, for example, Harlow and Lane (1988) and (1999), loc. cit.; Kontermann and Dübel, Antibody Engineering, Springer, 2nd ed. 2010 and Little, Recombinant Antibodies for Immunotherapy, Cambridge University Press 2009. Such immunoglobulin single variable domain encompasses not only an isolated antibody single variable domain polypeptide, but also larger polypeptides that comprise one or more monomers of an antibody single variable domain polypeptide sequence.
In line with this definition all above described embodiments of the term antibody can be subsumed under the term “antibody construct”. Said term also includes diabodies or Dual-Affinity Re-Targeting (DART) antibodies. Further envisaged are (bispecific) single chain diabodies, tandem diabodies (Tandab's), “minibodies” exemplified by a structure which is as follows: (VH-VL-CH3)₂, (scFv-CH3)₂or (scFv-CH3-scFv)₂, “Fc DART” antibodies and “IgG DART” antibodies, and multibodies such as triabodies. Immunoglobulin single variable domains encompass not only an isolated antibody single variable domain polypeptide, but also larger polypeptides that comprise one or more monomers of an antibody single variable domain polypeptide sequence.
Various procedures are known in the art and may be used for the production of such antibody constructs (antibodies and/or fragments). Thus, (antibody) derivatives can be produced by peptidomimetics. Further, techniques described for the production of single chain antibodies (see, inter alia, U.S. Pat. No. 4,946,778, Kontermann and Dübel (2010), loc. cit. and Little (2009), loc. cit.) can be adapted to produce single chain antibodies specific for elected polypeptide(s). Also, transgenic animals may be used to express humanized antibodies specific for polypeptides and fusion proteins of this invention. For the preparation of monoclonal antibodies, any technique, providing antibodies produced by continuous cell line cultures can be used. Examples for such techniques include the hybridoma technique (Köhler and Milstein Nature 256 (1975), 495-497), the trioma technique, the human B-cell hybridoma technique (Kozbor, Immunology Today 4 (1983), 72) and the EBV-hybridoma technique to produce human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), 77-96). Surface plasmon resonance as employed in the BIAcore system can be used to increase the efficiency of phage antibodies which bind to an epitope of a target polypeptide, such as CDH19 (Schier, Human Antibodies Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol. Methods 183 (1995), 7-13). It is also envisaged in the context of this invention that the term “antibody” comprises antibody constructs, which may be expressed in a host as described herein below, e.g. antibody constructs which may be transfected and/or transduced via, inter alia, viruses or plasmid vectors.
Furthermore, the term “antibody” as employed in the invention also relates to derivatives or variants of the antibodies described herein which display the same specificity as the described antibodies. Accordingly, the term “antibody” also subsumes antibody constructs such as different types of fragments of antibodies, which still are characterized by the feature of specific binding for CDH19.
The terms “antigen-binding domain”, “antigen-binding fragment” and “antibody binding region” when used herein refer to a part of an antibody molecule that comprises amino acids responsible for the specific binding between antibody and antigen. The part of the antigen that is specifically recognized and bound by the antibody is referred to as the “epitope” as described herein above. As mentioned above, an antigen-binding domain may typically comprise an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH); however, it does not have to comprise both. Fd fragments, for example, have two VH regions and often retain some antigen-binding function of the intact antigen-binding domain. Examples of antigen-binding fragments of an antibody include (1) a Fab fragment, a monovalent fragment having the VL, VH, CL and CH1 domains; (2) a F(ab′)2 fragment, a bivalent fragment having two Fab fragments linked by a disulfide bridge at the hinge region; (3) a Fd fragment having the two VH and CH1 domains; (4) a Fv fragment having the VL and VH domains of a single arm of an antibody, (5) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which has a VH domain; (6) an isolated complementarity determining region (CDR), and (7) a single chain Fv (scFv). Although the two domains of the Fv fragment, VL and VH are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Huston et al. (1988) Proc. Natl. Acad. Sci USA 85:5879-5883). These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are evaluated for function in the same manner as are intact antibodies.
The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations and/or post-translation modifications (e.g., isomerizations, amidations) that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler et al., Nature, 256: 495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature, 352: 624-628 (1991) and Marks et al., J. Mol. Biol., 222: 581-597 (1991), for example.
The term “human antibody” includes antibodies having variable and constant regions corresponding substantially to human germline immunoglobulin sequences known in the art, including, for example, those described by Kabat et al. (See Kabat et al. (1991) loc. cit.). The human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs, and in particular, CDR3. The human antibody can have at least one, two, three, four, five, or more positions replaced with an amino acid residue that is not encoded by the human germline immunoglobulin sequence. It is emphasized that the definition of human antibodies as used herein also contemplates fully human antibodies, which include only non-artificially and/or genetically altered human sequences of antibodies as those can be derived by technologies using systems such as the Xenomice.
Examples of “antibody variants” include humanized variants of non-human antibodies, “affinity matured” antibodies (see, e.g. Hawkins et al. J. Mol. Biol. 254, 889-896 (1992) and Lowman et al., Biochemistry 30, 10832-10837 (1991)) and antibody mutants with altered effector function (s) (see, e.g., U.S. Pat. No. 5,648,260, Kontermann and Dübel (2010), loc. cit. and Little (2009), loc. cit.).
As used herein, “in vitro generated antibody” refers to an antibody where all or part of the variable region (e.g., at least one CDR) is generated in a non-immune cell selection (e.g., an in vitro phage display, protein chip or any other method in which candidate sequences can be tested for their ability to bind to an antigen). This term thus preferably excludes sequences generated by genomic rearrangement in an immune cell.
The pairing of a VH and VL together forms a single antigen-binding site. The CH domain most proximal to VH is designated as CH1. Each L chain is linked to an H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. The VH and VL domains consist of four regions of relatively conserved sequences called framework regions (FR1, FR2, FR3, and FR4), which form a scaffold for three regions of hypervariable sequences (complementarity determining regions, CDRs). The CDRs contain most of the residues responsible for specific interactions of the antibody with the antigen. CDRs are referred to as CDR 1, CDR2, and CDR3. Accordingly, CDR constituents on the heavy chain are referred to as H1, H2, and H3, while CDR constituents on the light chain are referred to as L1, L2, and L3.
The term “variable” refers to the portions of the immunoglobulin domains that exhibit variability in their sequence and that are involved in determining the specificity and binding affinity of a particular antibody (i.e., the “variable domain(s)”). Variability is not evenly distributed throughout the variable domains of antibodies; it is concentrated in sub-domains of each of the heavy and light chain variable regions. These sub-domains are called “hypervariable” regions or “complementarity determining regions” (CDRs). The more conserved (i.e., non-hypervariable) portions of the variable domains are called the “framework” regions (FRM). The variable domains of naturally occurring heavy and light chains each comprise four FRM regions, largely adopting a β-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the β-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRM and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site (see Kabat et al., loc. cit.). The constant domains are not directly involved in antigen binding, but exhibit various effector functions, such as, for example, antibody-dependent, cell-mediated cytotoxicity and complement activation.
The terms “CDR”, and its plural “CDRs”, refer to a complementarity determining region (CDR) of which three make up the binding character of a light chain variable region (CDRL1, CDRL2 and CDRL3) and three make up the binding character of a heavy chain variable region (CDRH1, CDRH2 and CDRH3). CDRs contribute to the functional activity of an antibody molecule and are separated by amino acid sequences that comprise scaffolding or framework regions. The exact definitional CDR boundaries and lengths are subject to different classification and numbering systems. CDRs may therefore be referred to by Kabat, Chothia, contact or any other boundary definitions, including the numbering system described herein. Despite differing boundaries, each of these systems has some degree of overlap in what constitutes the so called “hypervariable regions” within the variable sequences. CDR definitions according to these systems may therefore differ in length and boundary areas with respect to the adjacent framework region. See for example Kabat, Chothia, and/or MacCallum (Kabat et al., loc. cit.; Chothia et al., J. Mol. Biol, 1987, 196: 901; and MacCallum et al., J. Mol. Biol, 1996, 262: 732). However, the numbering in accordance with the so-called Kabat system is preferred. The CDR3 of the light chain and, particularly, CDR3 of the heavy chain may constitute the most important determinants in antigen binding within the light and heavy chain variable regions. In some antibodies, the heavy chain CDR3 appears to constitute the major area of contact between the antigen and the antibody. In vitro selection schemes in which CDR3 alone is varied can be used to vary the binding properties of an antibody or determine which residues contribute to the binding of an antigen.
In one embodiment, the antibody of the invention may comprise from one to six of the exemplary CDRs described herein. The antibodies of the invention may be of any type including IgM, IgG (including IgG1, IgG2, IgG3, IgG4), IgD, IgA, or IgE antibody. In a specific embodiment the antigen binding protein is an IgG type antibody, e.g., a IgG1 antibody.
In one embodiment, the antibody of the invention may be a mutlispecific antibody, and notably a bispecfic antibody, also sometimes referred to as “diabodies.” These are antibodies that bind to two or more different antigens or different epitopes on a single antigen. In certain embodiments, a bispecific antibody binds CDH19 and an antigen on a human effector cell (e.g., T cell). Such antibodies are useful in targeting an effector cell response against a CDH19 expressing cells, such as a tumor cell. In preferred embodiments, the human effector cell antigen is CD3 (see corresponding formats e.g. in WO 2008/119567. Methods of making bispecific antibodies are known in the art. One such method involves engineering the Fc portion of the heavy chains such as to create “knobs” and “holes” which facilitate heterodimer formation of the heavy chains when co-expressed in a cell. U.S. Pat. No. 7,695,963. Another method also involves engineering the Fc portion of the heavy chain but uses electrostatic steering to encourage heterodimer formation while discouraging homodimer formation of the heavy chains when co-expressed in a cell. WO 2009/089004, which is incorporated herein by reference in its entirety.
In one embodiment, antibody of the invention is a minibody. Minibodies are minimized antibody-like proteins comprising a scFv joined to a CH3 domain. Hu et al., 1996, Cancer Res. 56:3055-3061.
In one embodiment, the antibody of the invention is a domain antibody; see, for example U.S. Pat. No. 6,248,516. Domain antibodies (dAbs) are functional binding domains of antibodies, corresponding to the variable regions of either the heavy (VH) or light (VL) chains of human antibodies. dABs have a molecular weight of approximately 13 kDa, or less than one-tenth the size of a full antibody. dABs are well expressed in a variety of hosts including bacterial, yeast, and mammalian cell systems. In addition, dAbs are highly stable and retain activity even after being subjected to harsh conditions, such as freeze-drying or heat denaturation. See, for example, U.S. Pat. Nos. 6,291,158; 6,582,915; 6,593,081; 6,172,197; US Serial No. 2004/0110941; European Patent 0368684; U.S. Pat. No. 6,696,245, WO04/058821, WO04/003019 and WO03/002609.
In one embodiment, the antibody of the invention is an antibody fragment, that is a fragment of any of the antibodies outlined herein that retain binding specificity to CDH19. In various embodiments, the antibody binding proteins comprise, but are not limited to, a F(ab), F(ab′), F(ab′)2, Fv, or a single chain Fv fragments. At a minimum, an antibody, as meant herein, comprises a polypeptide that can bind specifically to CDH19 comprising all or part of a light or heavy chain variable region, such as one or more CDRs.
Naturally occurring antibodies typically include a signal sequence, which directs the antibody into the cellular pathway for protein secretion and which is typically not present in the mature antibody. A polynucleotide encoding an antibody of the invention may encode a naturally occurring a signal sequence or a heterologous signal sequence as described below.
“Consisting essentially of” means that the amino acid sequence can vary by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% relative to the recited SEQ ID NO: sequence and still retain biological activity, as described herein.
In some embodiments, the antibodies of the invention are isolated proteins or substantially pure proteins. An “isolated” protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, for example constituting at least about 5%, or at least about 50% by weight of the total protein in a given sample. It is understood that the isolated protein may constitute from 5 to 99.9% by weight of the total protein content depending on the circumstances. For example, the protein may be made at a significantly higher concentration through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels. The definition includes the production of an antigen binding protein in a wide variety of organisms and/or host cells that are known in the art.
For amino acid sequences, sequence identity and/or similarity is determined by using standard techniques known in the art, including, but not limited to, the local sequence identity algorithm of Smith and Waterman, 1981, Adv. Appl. Math. 2:482, the sequence identity alignment algorithm of Needleman and Wunsch, 1970, J. Mol. Biol. 48:443, the search for similarity method of Pearson and Lipman, 1988, Proc. Nat. Acad. Sci. U.S.A. 85:2444, computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, Wis.), the Best Fit sequence program described by Devereux et al., 1984, Nucl. Acid Res. 12:387-395, preferably using the default settings, or by inspection. Preferably, percent identity is calculated by FastDB based upon the following parameters: mismatch penalty of 1; gap penalty of 1; gap size penalty of 0.33; and joining penalty of 30, “Current Methods in Sequence Comparison and Analysis,” Macromolecule Sequencing and Synthesis, Selected Methods and Applications, pp 127-149 (1988), Alan R. Liss, Inc.
An example of a useful algorithm is PILEUP. PILEUP creates a multiple sequence alignment from a group of related sequences using progressive, pairwise alignments. It can also plot a tree showing the clustering relationships used to create the alignment. PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle, 1987, J. Mol. Evol. 35:351-360; the method is similar to that described by Higgins and Sharp, 1989, CABIOS 5:151-153. Useful PILEUP parameters including a default gap weight of 3.00, a default gap length weight of 0.10, and weighted end gaps.
Another example of a useful algorithm is the BLAST algorithm, described in: Altschul et al., 1990, J. Mol. Biol. 215:403-410; Altschul et al., 1997, Nucleic Acids Res. 25:3389-3402; and Karin et al., 1993, Proc. Natl. Acad. Sci. U.S.A. 90:5873-5787. A particularly useful BLAST program is the WU-BLAST-2 program which was obtained from Altschul et al., 1996, Methods in Enzymology 266:460-480. WU-BLAST-2 uses several search parameters, most of which are set to the default values. The adjustable parameters are set with the following values: overlap span=1, overlap fraction=0.125, word threshold (T)=II. The HSP S and HSP S2 parameters are dynamic values and are established by the program itself depending upon the composition of the particular sequence and composition of the particular database against which the sequence of interest is being searched; however, the values may be adjusted to increase sensitivity.
An additional useful algorithm is gapped BLAST as reported by Altschul et al., 1993, Nucl. Acids Res. 25:3389-3402. Gapped BLAST uses BLOSUM-62 substitution scores; threshold T parameter set to 9; the two-hit method to trigger ungapped extensions, charges gap lengths of k a cost of 10+k; Xu set to 16, and Xg set to 40 for database search stage and to 67 for the output stage of the algorithms. Gapped alignments are triggered by a score corresponding to about 22 bits.
Generally, the amino acid homology, similarity, or identity between individual variant CDRs are at least 80% to the sequences depicted herein, and more typically with preferably increasing homologies or identities of at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and almost 100%. In a similar manner, “percent (%) nucleic acid sequence identity” with respect to the nucleic acid sequence of the binding proteins identified herein is defined as the percentage of nucleotide residues in a candidate sequence that are identical with the nucleotide residues in the coding sequence of the antigen binding protein. A specific method utilizes the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.
Generally, the nucleic acid sequence homology, similarity, or identity between the nucleotide sequences encoding individual variant CDRs and the nucleotide sequences depicted herein are at least 80%, and more typically with preferably increasing homologies or identities of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, and almost 100%.
Thus, a “variant CDR” is one with the specified homology, similarity, or identity to the parent CDR of the invention, and shares biological function, including, but not limited to, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the specificity and/or activity of the parent CDR.
While the site or region for introducing an amino acid sequence variation is predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed antigen binding protein CDR variants screened for the optimal combination of desired activity. Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example, M13 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of antigen binding protein activities, such as CDH19 binding.
The term “amino acid” or “amino acid residue” typically refers to an amino acid having its art recognized definition such as an amino acid selected from the group consisting of: alanine (Ala or A); arginine (Arg or R); asparagine (Asn or N); aspartic acid (Asp or D); cysteine (Cys or C); glutamine (Gln or Q); glutamic acid (Glu or E); glycine (Gly or G); histidine (His or H); isoleucine (He or I): leucine (Leu or L); lysine (Lys or K); methionine (Met or M); phenylalanine (Phe or F); pro line (Pro or P); serine (Ser or S); threonine (Thr or T); tryptophan (Trp or W); tyrosine (Tyr or Y); and valine (Val or V), although modified, synthetic, or rare amino acids may be used as desired. Generally, amino acids can be grouped as having a nonpolar side chain (e.g., Ala, Cys, He, Leu, Met, Phe, Pro, Val); a negatively charged side chain (e.g., Asp, Glu); a positively charged sidechain (e.g., Arg, His, Lys); or an uncharged polar side chain (e.g., Asn, Cys, Gln, Gly, His, Met, Phe, Ser, Thr, Trp, and Tyr).
The term “hypervariable region” (also known as “complementarity determining regions” or CDRs) when used herein refers to the amino acid residues of an antibody which are (usually three or four short regions of extreme sequence variability) within the V-region domain of an immunoglobulin which form the antigen-binding site and are the main determinants of antigen specificity. There are at least two methods for identifying the CDR residues: (1) An approach based on cross-species sequence variability (i. e., Kabat et al., loc. cit.); and (2) An approach based on crystallographic studies of antigen-antibody complexes (Chothia, C. et al., J. Mol. Biol. 196: 901-917 (1987)). However, to the extent that two residue identification techniques define regions of overlapping, but not identical regions, they can be combined to define a hybrid CDR. However, in general, the CDR residues are preferably identified in accordance with the so-called Kabat (numbering) system.
The term “framework region” refers to the art-recognized portions of an antibody variable region that exist between the more divergent (i.e., hypervariable) CDRs. Such framework regions are typically referred to as frameworks 1 through 4 (FR1, FR2, FR3, and FR4) and provide a scaffold for the presentation of the six CDRs (three from the heavy chain and three from the light chain) in three dimensional space, to form an antigen-binding surface.
Typically, CDRs form a loop structure that can be classified as a canonical structure. The term “canonical structure” refers to the main chain conformation that is adopted by the antigen binding (CDR) loops. From comparative structural studies, it has been found that five of the six antigen binding loops have only a limited repertoire of available conformations. Each canonical structure can be characterized by the torsion angles of the polypeptide backbone. Correspondent loops between antibodies may, therefore, have very similar three dimensional structures, despite high amino acid sequence variability in most parts of the loops (Chothia and Lesk, J. Mol. Biol., 1987, 196: 901; Chothia et al., Nature, 1989, 342: 877; Martin and Thornton, J. Mol. Biol, 1996, 263: 800, each of which is incorporated by reference in its entirety). Furthermore, there is a relationship between the adopted loop structure and the amino acid sequences surrounding it. The conformation of a particular canonical class is determined by the length of the loop and the amino acid residues residing at key positions within the loop, as well as within the conserved framework (i.e., outside of the loop). Assignment to a particular canonical class can therefore be made based on the presence of these key amino acid residues. The term “canonical structure” may also include considerations as to the linear sequence of the antibody, for example, as catalogued by Kabat (Kabat et al., loc. cit.). The Kabat numbering scheme (system) is a widely adopted standard for numbering the amino acid residues of an antibody variable domain in a consistent manner and is the preferred scheme applied in the present invention as also mentioned elsewhere herein. Additional structural considerations can also be used to determine the canonical structure of an antibody. For example, those differences not fully reflected by Kabat numbering can be described by the numbering system of Chothia et al and/or revealed by other techniques, for example, crystallography and two or three-dimensional computational modeling. Accordingly, a given antibody sequence may be placed into a canonical class which allows for, among other things, identifying appropriate chassis sequences (e.g., based on a desire to include a variety of canonical structures in a library). Kabat numbering of antibody amino acid sequences and structural considerations as described by Chothia et al., loc. cit. and their implications for construing canonical aspects of antibody structure, are described in the literature.
CDR3 is typically the greatest source of molecular diversity within the antibody-binding site. H3, for example, can be as short as two amino acid residues or greater than 26 amino acids. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known in the art. For a review of the antibody structure, see Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, eds. Harlow et al., 1988. One of skill in the art will recognize that each subunit structure, e.g., a CH, VH, CL, VL, CDR, FR structure, comprises active fragments, e.g., the portion of the VH, VL, or CDR subunit the binds to the antigen, i.e., the antigen-binding fragment, or, e.g., the portion of the CH subunit that binds to and/or activates, e.g., an Fc receptor and/or complement. The CDRs typically refer to the Kabat CDRs, as described in Sequences of Proteins of immunological Interest, US Department of Health and Human Services (1991), eds. Kabat et al. Another standard for characterizing the antigen binding site is to refer to the hypervariable loops as described by Chothia. See, e.g., Chothia, et al. (1987; J. Mol. Biol. 227:799-817); and Tomlinson et al. (1995) EMBO J. 14: 4628-4638. Still another standard is the AbM definition used by Oxford Molecular's AbM antibody modeling software. See, generally, e.g., Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Antibody Engineering Lab Manual (Ed.: Duebel, S. and Kontermann, R., Springer-Verlag, Heidelberg). Embodiments described with respect to Kabat CDRs can alternatively be implemented using similar described relationships with respect to Chothia hypervariable loops or to the AbM-defined loops.
The sequence of antibody genes after assembly and somatic mutation is highly varied, and these varied genes are estimated to encode 10¹⁰different antibody molecules (Immunoglobulin Genes, 2^nded., eds. Jonio et al., Academic Press, San Diego, Calif., 1995). Accordingly, the immune system provides a repertoire of immunoglobulins. The term “repertoire” refers to at least one nucleotide sequence derived wholly or partially from at least one sequence encoding at least one immunoglobulin. The sequence(s) may be generated by rearrangement in vivo of the V, D, and J segments of heavy chains, and the V and J segments of light chains. Alternatively, the sequence(s) can be generated from a cell in response to which rearrangement occurs, e.g., in vitro stimulation. Alternatively, part or all of the sequence(s) may be obtained by DNA splicing, nucleotide synthesis, mutagenesis, and other methods, see, e.g., U.S. Pat. No. 5,565,332. A repertoire may include only one sequence or may include a plurality of sequences, including ones in a genetically diverse collection.
The term “binding molecule” or “antibody construct” in the sense of the present disclosure indicates any molecule capable of (specifically) binding to, interacting with or recognizing the target molecule CDH19. Such molecules or constructs may include proteinaceous parts and non-proteinaceous parts (e.g. chemical linkers or chemical cross-linking agents such as glutaraldehyde).
The term “multispecific” as used herein refers to a binding molecule which is an antibody construct and comprises at least a first and a second binding domain, wherein the first binding domain is capable of binding to one antigen or target, and the second binding domain is capable of binding to another antigen or target. Accordingly, antibody constructs according to the invention comprise at least a specificity for CDH19. The “antibody construct” of the invention also comprises multispecific binding molecules such as e.g. trispecific binding molecules, the latter ones including three binding domains.
It is also envisaged that the antibody construct of the invention has, in addition to its function to bind to the target molecules CDH19 and CD3, a further function. In this format, the antibody construct is a bi-, tri- or multifunctional antibody construct by targeting plasma cells through binding to CDH19, mediating cytotoxic T cell activity through CD3 binding and providing a further function such as a fully functional Fc constant domain mediating antibody-dependent cellular cytotoxicity through recruitment of effector cells like NK cells, a label (fluorescent etc.), a therapeutic agent such as, e.g. a toxin or radionuclide, and/or means to enhance serum half-life, etc.
The term “binding domain” characterizes in connection with the present invention a domain which is capable of specifically binding to/interacting with a given target epitope or a given target site on the target molecule CDH19.
Binding domains can be derived from a binding domain donor such as for example an antibody. It is envisaged that a binding domain of the present invention comprises at least said part of any of the aforementioned binding domains that is required for binding to/interacting with a given target epitope or a given target site on the target molecule CDH19.
It is envisaged that the binding domain of the aforementioned binding domain donors is characterized by that part of these donors that is responsible for binding the respective target, i.e. when that part is removed from the binding domain donor, said donor loses its binding capability. “Loses” means a reduction of at least 50% of the binding capability when compared with the binding donor. Methods to map these binding sites are well known in the art—it is therefore within the standard knowledge of the skilled person to locate/map the binding site of a binding domain donor and, thereby, to “derive” said binding domain from the respective binding domain donors.
The term “epitope” refers to a site on an antigen to which a binding domain, such as an antibody or immunoglobulin or derivative or fragment of an antibody or of an immunoglobulin, specifically binds. An “epitope” is antigenic and thus the term epitope is sometimes also referred to herein as “antigenic structure” or “antigenic determinant”. Thus, the binding domain is an “antigen-interaction-site”. Said binding/interaction is also understood to define a “specific recognition”. In one example, said binding domain which (specifically) binds to/interacts with a given target epitope or a given target site on the target molecule CDH19 is an antibody or immunoglobulin, and said binding domain is a VH and/or VL region of an antibody or of an immunoglobulin.
“Epitopes” can be formed both by contiguous amino acids or non-contiguous amino acids juxtaposed by tertiary folding of a protein. A “linear epitope” is an epitope where an amino acid primary sequence comprises the recognized epitope. A linear epitope typically includes at least 3 or at least 4, and more usually, at least 5 or at least 6 or at least 7, for example, about 8 to about 10 amino acids in a unique sequence.
A “conformational epitope”, in contrast to a linear epitope, is an epitope wherein the primary sequence of the amino acids comprising the epitope is not the sole defining component of the epitope recognized (e.g., an epitope wherein the primary sequence of amino acids is not necessarily recognized by the binding domain). Typically a conformational epitope comprises an increased number of amino acids relative to a linear epitope. With regard to recognition of conformational epitopes, the binding domain recognizes a three-dimensional structure of the antigen, preferably a peptide or protein or fragment thereof (in the context of the present invention, the antigen for one of the binding domains is comprised within the CDH19 protein). For example, when a protein molecule folds to form a three-dimensional structure, certain amino acids and/or the polypeptide backbone forming the conformational epitope become juxtaposed enabling the antibody to recognize the epitope. Methods of determining the conformation of epitopes include, but are not limited to, x-ray crystallography, two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy and site-directed spin labelling and electron paramagnetic resonance (EPR) spectroscopy. Moreover, the provided examples describe a further method to characterize a given binding domain by way of binning, which includes a test whether the given binding domain binds to one or more epitope cluster(s) of a given protein, in particular CDH19.
As used herein, the term “epitope cluster” denotes the entirety of epitopes lying in a defined contiguous stretch of an antigen. An epitope cluster can comprise one, two or more epitopes. The concept of epitope cluster is also used in the characterization of the features of the antibody or antigen binding fragment thereof of the invention.
The terms “(capable of) binding to”, “specifically recognizing”, “directed to” and “reacting with” mean in accordance with this invention that a binding domain is capable of specifically interacting with one or more, preferably at least two, more preferably at least three and most preferably at least four amino acids of an epitope.
As used herein, the terms “specifically interacting”, “specifically binding” or “specifically bind(s)” mean that a binding domain exhibits appreciable affinity for a particular protein or antigen and, generally, does not exhibit significant reactivity with proteins or antigens other than CDH19. “Appreciable affinity” includes binding with an affinity of about 10⁻⁶M (KD) or stronger. Preferably, binding is considered specific when binding affinity is about 10⁻¹²to 10⁻⁸M, 10⁻¹²to 10⁻⁹M, 10⁻¹²to 10⁻¹⁰M, 10⁻¹¹to 10⁻⁸M, preferably of about 10⁻¹¹to 10⁻⁹M. Whether a binding domain specifically reacts with or binds to a target can be tested readily by, inter alia, comparing the reaction of said binding domain with a target protein or antigen with the reaction of said binding domain with proteins or antigens other than CDH19. Preferably, a binding domain of the invention does not essentially bind or is not capable of binding to proteins or antigens other than CDH19.
The term “does not essentially bind”, or “is not capable of binding” means that a binding domain of the present invention does not bind another protein or antigen other than CDH19, i.e., does not show reactivity of more than 30%, preferably not more than 20%, more preferably not more than 10%, particularly preferably not more than 9%, 8%, 7%, 6% or 5% with proteins or antigens other than CDH19, whereby binding to CDH19, respectively, is set to be 100%.
Specific binding is believed to be effected by specific motifs in the amino acid sequence of the binding domain and the antigen. Thus, binding is achieved as a result of their primary, secondary and/or tertiary structure as well as the result of secondary modifications of said structures. The specific interaction of the antigen-interaction-site with its specific antigen may result in a simple binding of said site to the antigen. Moreover, the specific interaction of the antigen-interaction-site with its specific antigen may alternatively or additionally result in the initiation of a signal, e.g. due to the induction of a change of the conformation of the antigen, an oligomerization of the antigen, etc.
Proteins (including fragments thereof, preferably biologically active fragments, and peptides, usually having less than 30 amino acids) comprise one or more amino acids coupled to each other via a covalent peptide bond (resulting in a chain of amino acids). The term “polypeptide” as used herein describes a group of molecules, which consist of more than 30 amino acids. Polypeptides may further form multimers such as dimers, trimers and higher oligomers, i.e. consisting of more than one polypeptide molecule. Polypeptide molecules forming such dimers, trimers etc. may be identical or non-identical. The corresponding higher order structures of such multimers are, consequently, termed homo- or heterodimers, homo- or heterotrimers etc. An example for a hereteromultimer is an antibody molecule, which, in its naturally occurring form, consists of two identical light polypeptide chains and two identical heavy polypeptide chains. The terms “polypeptide” and “protein” also refer to naturally modified polypeptides/proteins wherein the modification is effected e.g. by post-translational modifications like glycosylation, acetylation, phosphorylation and the like. A “polypeptide” when referred to herein may also be chemically modified such as pegylated. Such modifications are well known in the art.
“Isolated” when used to describe the antibody or antigen binding fragment thereof or antibody construct disclosed herein, refers to the antibody or antigen binding fragment thereof or antibody construct disclosed herein that has been identified, separated and/or recovered from a component of its production environment. Preferably, the isolated the antibody or antigen binding fragment thereof or antibody construct disclosed herein is free of association with all other components from its production environment. Contaminant components of its production environment, such as that resulting from recombinant transfected cells, are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the the antibody or antigen binding fragment thereof or antibody construct will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Ordinarily, however, an isolated antibody will be prepared by at least one purification step.
Amino acid sequence modifications of the the antibody or antigen binding fragment thereof or antibody construct described herein are contemplated. For example, it may be desirable to improve the binding affinity and/or other biological properties of the antibody. Amino acid sequence variants of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein are prepared by introducing appropriate nucleotide changes into the the antibody or antigen binding fragment thereof or antibody construct nucleic acid, or by peptide synthesis.
Such modifications include, for example, deletions from, and/or insertions into, and/or substitutions of, residues within the amino acid sequences of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein. Any combination of deletion, insertion, and substitution is made to arrive at the final construct, provided that the final construct possesses the desired characteristics. The amino acid changes also may alter post-translational processes of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein, such as changing the number or position of glycosylation sites. Preferably, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids may be substituted in a CDR, while 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 25 amino acids may be substituted in the framework regions (FRs). The substitutions are preferably conservative substitutions as described herein. Additionally or alternatively, 1, 2, 3, 4, 5, or 6 amino acids may be inserted or deleted in each of the CDRs (of course, dependent on their length), while 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 25 amino acids may be inserted or deleted in each of the FRs.
A useful method for identification of certain residues or regions of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein that are preferred locations for mutagenesis is called “alanine scanning mutagenesis” as described by Cunningham and Wells in Science, 244: 1081-1085 (1989). Here, a residue or group of target residues within the the antibody or antigen binding fragment thereof or antibody construct disclosed herein is/are identified (e.g. charged residues such as arg, asp, his, lys, and glu) and replaced by a neutral or negatively charged amino acid (most preferably alanine or polyalanine) to affect the interaction of the amino acids with the epitope.
Those amino acid locations demonstrating functional sensitivity to the substitutions then are refined by introducing further or other variants at, or for, the sites of substitution. Thus, while the site for introducing an amino acid sequence variation is predetermined, the nature of the mutation per se needs not to be predetermined. For example, to analyze the performance of a mutation at a given site, ala scanning or random mutagenesis is conducted at a target codon or region and the expressed the antibody or antigen binding fragment thereof or antibody construct disclosed herein variants are screened for the desired activity.
Preferably, amino acid sequence insertions include amino- and/or carboxyl-terminal fusions ranging in length from 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 residues to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. An insertional variant of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein includes the fusion to the N- or C-terminus of the antibody to an enzyme or a fusion to a polypeptide which increases the serum half-life of the antibody.
Another type of variant is an amino acid substitution variant. These variants have preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid residues in the the antibody or antigen binding fragment thereof or antibody construct disclosed herein replaced by a different residue. The sites of greatest interest for substitutional mutagenesis include the CDRs of the heavy and/or light chain, in particular the hypervariable regions, but FR alterations in the heavy and/or light chain are also contemplated.
For example, if a CDR sequence encompasses 6 amino acids, it is envisaged that one, two or three of these amino acids are substituted. Similarly, if a CDR sequence encompasses 15 amino acids it is envisaged that one, two, three, four, five or six of these amino acids are substituted.
Generally, if amino acids are substituted in one or more or all of the CDRs of the heavy and/or light chain, it is preferred that the then-obtained “substituted” sequence is at least 60%, more preferably 65%, even more preferably 70%, particularly preferably 75%, more particularly preferably 80% identical to the “original” CDR sequence. This means that it is dependent of the length of the CDR to which degree it is identical to the “substituted” sequence. For example, a CDR having 5 amino acids is preferably 80% identical to its substituted sequence in order to have at least one amino acid substituted. Accordingly, the CDRs of the the antibody or antigen binding fragment thereof or antibody construct disclosed herein may have different degrees of identity to their substituted sequences, e.g., CDRL1 may have 80%, while CDRL3 may have 90%.
Preferred substitutions (or replacements) are conservative substitutions. However, any substitution (including non-conservative substitution or one or more from the “exemplary substitutions” listed in Table 1, below) is envisaged as long as the the antibody or antigen binding fragment thereof or antibody construct retains its capability to bind to CDH19 v and/or its CDRs have an identity to the then substituted sequence (at least 60%, more preferably 65%, even more preferably 70%, particularly preferably 75%, more particularly preferably 80% identical to the “original” CDR sequence).
Conservative substitutions are shown in Table 1 under the heading of “preferred substitutions”. If such substitutions result in a change in biological activity, then more substantial changes, denominated “exemplary substitutions” in Table 1, or as further described below in reference to amino acid classes, may be introduced and the products screened for a desired characteristic.

TABLE 1

Amino Acid Substitutions

		Preferred
Original	Exemplary Substitutions	Substitutions

Ala (A)	val, leu, ile	val
Arg (R)	lys, gin, asn	lys
Asn (N)	gin, his, asp, lys, arg	gin
Asp (D)	glu, asn	glu
Cys (C)	ser, ala	ser
Gln (Q)	asn, glu	asn
Glu (E)	asp, gin	Asp
Gly (G)	ala	Ala
His (H)	asn, gin, lys, arg	Arg
Ile (I)	leu, val, met, ala, phe	Leu
Leu (L)	norleucine, ile, val, met, ala	Ile
Lys (K)	arg, gin, asn	Arg
Met (M)	leu, phe, ile	Leu
Phe (F)	leu, val, ile, ala, tyr	Tyr
Pro (P)	ala	Ala
Ser (S)	thr	Thr
Thr (T)	ser	Ser
Trp (W)	tyr, phe	Tyr
Tyr (Y)	trp, phe, thr, ser	Phe
Val (V)	ile, leu, met, phe, ala	Leu

Substantial modifications in the biological properties of the the antibody or antigen binding fragment thereof or antibody construct of the present invention are accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side-chain properties: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophilic: cys, ser, thr; (3) acidic: asp, glu; (4) basic: asn, gin, his, lys, arg; (5) residues that influence chain orientation: gly, pro; and (6) aromatic: trp, tyr, phe.
Non-conservative substitutions will entail exchanging a member of one of these classes for another class. Any cysteine residue not involved in maintaining the proper conformation of the the antibody or antigen binding fragment thereof or antibody construct may be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine bond(s) may be added to the antibody to improve its stability (particularly where the antibody is an antibody fragment such as an Fv fragment).
A particularly preferred type of substitutional variant involves substituting one or more hypervariable region residues of a parent antibody (e. g. a humanized or human antibody). Generally, the resulting variant(s) selected for further development will have improved biological properties relative to the parent antibody from which they are generated. A convenient way for generating such substitutional variants involves affinity maturation using phage display. Briefly, several hypervariable region sites (e. g. 6-7 sites) are mutated to generate all possible amino acid substitutions at each site. The antibody variants thus generated are displayed in a monovalent fashion from filamentous phage particles as fusions to the gene III product of M13 packaged within each particle. The phage-displayed variants are then screened for their biological activity (e. g. binding affinity) as herein disclosed. In order to identify candidate hypervariable region sites for modification, alanine scanning mutagenesis can be performed to identify hypervariable region residues contributing significantly to antigen binding. Alternatively, or additionally, it may be beneficial to analyze a crystal structure of the antigen-antibody complex to identify contact points between the binding domain and, e.g., human CDH19. Such contact residues and neighbouring residues are candidates for substitution according to the techniques elaborated herein. Once such variants are generated, the panel of variants is subjected to screening as described herein and antibodies with superior properties in one or more relevant assays may be selected for further development.
Other modifications of the the antibody or antigen binding fragment thereof or antibody construct are contemplated herein. For example, the the antibody or antigen binding fragment thereof or antibody construct may be linked to one of a variety of non-proteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, polyoxyalkylenes, or copolymers of polyethylene glycol and polypropylene glycol. The the antibody or antigen binding fragment thereof or antibody construct may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization (for example, hydroxymethylcellulose or gelatine-microcapsules and poly (methylmethacylate) microcapsules, respectively), in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules), or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences, 16th edition, Oslo, A., Ed., (1980).
The the antibody or antigen binding fragment thereof or antibody construct disclosed herein may also be formulated as immuno-liposomes. A “liposome” is a small vesicle composed of various types of lipids, phospholipids and/or surfactant which is useful for delivery of a drug to a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to the lipid arrangement of biological membranes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); U.S. Pat. Nos. 4,485,045 and 4,544,545; and WO 97/38731 published Oct. 23, 1997. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556. Particularly useful liposomes can be generated by the reverse phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al. J. Biol. Chem. 257: 286-288 (1982) via a disulfide interchange reaction. A chemotherapeutic agent is optionally contained within the liposome. See Gabizon et al. J. National Cancer Inst. 81 (19) 1484 (1989).
When using recombinant techniques, the antibody, antigen binding fragment thereof or antibody construct can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the antibody, antigen binding fragment thereof or antibody construct is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, are removed, for example, by centrifugation or ultrafiltration. Carter et al., Bio/Technology 10: 163-167 (1992) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli.
The antibody, antigen binding fragment thereof or antibody construct composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred purification technique.
The term “agent” is used herein to denote a chemical compound, a mixture of chemical compounds, a biological macromolecule, or an extract made from biological materials.
The term “nucleic acid” is well known to the skilled person and encompasses DNA (such as cDNA) and RNA (such as mRNA). The nucleic acid can be double stranded and single stranded, linear and circular. Said nucleic acid molecule is preferably comprised in a vector which is preferably comprised in a host cell. Said host cell is, e.g. after transformation or transfection with the nucleic acid sequence of the invention, capable of expressing the the antibody or antigen binding fragment thereof or antibody construct disclosed herein. For that purpose the nucleic acid molecule is operatively linked with control sequences.
A vector is a nucleic acid molecule used as a vehicle to transfer (foreign) genetic material into a cell. The term “vector” encompasses—but is not restricted to—plasmids, viruses, cosmids and artificial chromosomes. In general, engineered vectors comprise an origin of replication, a multicloning site and a selectable marker. The vector itself is generally a nucleotide sequence, commonly a DNA sequence, that comprises an insert (transgene) and a larger sequence that serves as the “backbone” of the vector. Modern vectors may encompass additional features besides the transgene insert and a backbone: promoter, genetic marker, antibiotic resistance, reporter gene, targeting sequence, protein purification tag. Vectors called expression vectors (expression constructs) specifically are for the expression of the transgene in the target cell, and generally have control sequences such as a promoter sequence that drives expression of the transgene. Insertion of a vector into the target cell is usually called “transformation” for bacteria, “transfection” for eukaryotic cells, although insertion of a viral vector is also called “transduction”.
As used herein, the term “host cell” is intended to refer to a cell into which a nucleic acid encoding the the antibody or antigen binding fragment thereof or antibody construct of the invention is introduced by way of transformation, transfection and the like. It should be understood that such terms refer not only to the particular subject cell but to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.
As used herein, the term “expression” includes any step involved in the production of a the antibody or antigen binding fragment thereof or antibody construct of the invention including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion.
The term “control sequences” refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
A nucleic acid is “operably linked” when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, “operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.
The terms “host cell,” “target cell” or “recipient cell” are intended to include any individual cell or cell culture that can be or has/have been recipients for vectors or the incorporation of exogenous nucleic acid molecules, polynucleotides and/or proteins. It also is intended to include progeny of a single cell, and the progeny may not necessarily be completely identical (in morphology or in genomic or total DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. The cells may be prokaryotic or eukaryotic, and include but are not limited to bacteria, yeast cells, animal cells, and mammalian cells, e.g., murine, rat, macaque or human.
Suitable host cells include prokaryotes and eukaryotic host cells including yeasts, fungi, insect cells and mammalian cells.
The the antibody or antigen binding fragment thereof or antibody construct of the invention can be produced in bacteria. After expression, the the antibody or antigen binding fragment thereof or antibody construct of the invention, preferably the the antibody or antigen binding fragment thereof or antibody construct is isolated from the E. coli cell paste in a soluble fraction and can be purified through, e.g., affinity chromatography and/or size exclusion. Final purification can be carried out similar to the process for purifying antibody expressed e. g, in CHO cells.
In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for the the antibody or antigen binding fragment thereof or antibody construct of the invention. Saccharomyces cerevisiae, or common baker's yeast, is the most commonly used among lower eukaryotic host microorganisms. However, a number of other genera, species, and strains are commonly available and useful herein, such as Schizosaccharomyces pombe, Kluyveromyces hosts such as, e.g., K. lactis, K. fragilis (ATCC 12424), K. bulgaricus (ATCC 16045), K. wickeramii (ATCC 24178), K. waltii (ATCC 56500), K. drosophilarum (ATCC 36906), K. thermotolerans, and K. marxianus; yarrowia (EP 402 226); Pichia pastoris (EP 183 070); Candida; Trichoderma reesia (EP 244 234); Neurospora crassa; Schwanniomyces such as Schwanniomyces occidentalis; and filamentous fungi such as, e.g., Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts such as A. nidulans and A. niger.
Suitable host cells for the expression of glycosylated the antibody or antigen binding fragment thereof or antibody construct of the invention, preferably antibody derived antibody constructs are derived from multicellular organisms. Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruit fly), and Bombyx mori have been identified. A variety of viral strains for transfection are publicly available, e. g., the L-1 variant of Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV, and such viruses may be used as the virus herein according to the present invention, particularly for transfection of Spodoptera frugiperda cells.
Plant cell cultures of cotton, corn, potato, soybean, petunia, tomato, Arabidopsis and tobacco can also be utilized as hosts. Cloning and expression vectors useful in the production of proteins in plant cell culture are known to those of skill in the art. See e.g. Hiatt et al., Nature (1989) 342: 76-78, Owen et al. (1992) Bio/Technology 10: 790-794, Artsaenko et al. (1995) The Plant J 8: 745-750, and Fecker et al. (1996) Plant Mol Biol 32: 979-986.
However, interest has been greatest in vertebrate cells, and propagation of vertebrate cells in culture (tissue culture) has become a routine procedure. Examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol. 36: 59 (1977)); baby hamster kidney cells (BHK, ATCC CCL 10); Chinese hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77: 4216 (1980)); mouse sertoli cells (TM4, Mather, Biol. Reprod. 23: 243-251 (1980)); monkey kidney cells (CVI ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL1587); human cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2,1413 8065); mouse mammary tumor (MMT 060562, ATCC CCLS 1); TRI cells (Mather et al., Annals N. Y Acad. Sci. 383: 44-68 (1982)); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2).
When using recombinant techniques, the antibody or antigen binding fragment thereof or antibody construct of the invention can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the the antibody or antigen binding fragment thereof or antibody construct is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, are removed, for example, by centrifugation or ultrafiltration. Carter et al., Bio/Technology 10: 163-167 (1992) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 min. Cell debris can be removed by centrifugation. Where the antibody is secreted into the medium, supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit. A protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.
The the antibody or antigen binding fragment thereof or antibody construct of the invention prepared from the host cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred purification technique.
The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly (styrenedivinyl) benzene allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the antibody or antigen binding fragment thereof or antibody construct of the invention comprises a CH3 domain, the Bakerbond ABXMresin (J. T. Baker, Phillipsburg, N.J.) is useful for purification. Other techniques for protein purification such as fractionation on an ion-exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on heparin SEPHAROSE™ chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), chromato-focusing, SDS-PAGE, and ammonium sulfate precipitation are also available depending on the antibody to be recovered.
The term “culturing” refers to the in vitro maintenance, differentiation, growth, proliferation and/or propagation of cells under suitable conditions in a medium.
As used herein, the term “pharmaceutical composition” relates to a composition for administration to a patient, preferably a human patient. The particular preferred pharmaceutical composition of this invention comprises the antibody or antigen binding fragment thereof or antibody construct of the invention. Preferably, the pharmaceutical composition comprises suitable formulations of carriers, stabilizers and/or excipients. In a preferred embodiment, the pharmaceutical composition comprises a composition for parenteral, transdermal, intraluminal, intraarterial, intrathecal and/or intranasal administration or by direct injection into tissue. It is in particular envisaged that said composition is administered to a patient via infusion or injection. Administration of the suitable compositions may be effected by different ways, e.g., by intravenous, intraperitoneal, subcutaneous, intramuscular, topical or intradermal administration. In particular, the present invention provides for an uninterrupted administration of the suitable composition. As a non-limiting example, uninterrupted, i.e. continuous administration may be realized by a small pump system worn by the patient for metering the influx of therapeutic agent into the body of the patient. The pharmaceutical composition comprising the antibody or antigen binding fragment thereof or antibody construct of the invention can be administered by using said pump systems. Such pump systems are generally known in the art, and commonly rely on periodic exchange of cartridges containing the therapeutic agent to be infused. When exchanging the cartridge in such a pump system, a temporary interruption of the otherwise uninterrupted flow of therapeutic agent into the body of the patient may ensue. In such a case, the phase of administration prior to cartridge replacement and the phase of administration following cartridge replacement would still be considered within the meaning of the pharmaceutical means and methods of the invention together make up one “uninterrupted administration” of such therapeutic agent.
The continuous or uninterrupted administration of these antibody or antigen binding fragment thereof or antibody constructs of the invention may be intravenous or subcutaneous by way of a fluid delivery device or small pump system including a fluid driving mechanism for driving fluid out of a reservoir and an actuating mechanism for actuating the driving mechanism. Pump systems for subcutaneous administration may include a needle or a cannula for penetrating the skin of a patient and delivering the suitable composition into the patient's body. Said pump systems may be directly fixed or attached to the skin of the patient independently of a vein, artery or blood vessel, thereby allowing a direct contact between the pump system and the skin of the patient. The pump system can be attached to the skin of the patient for 24 hours up to several days. The pump system may be of small size with a reservoir for small volumes. As a non-limiting example, the volume of the reservoir for the suitable pharmaceutical composition to be administered can be between 0.1 and 50 ml.
The continuous administration may be transdermal by way of a patch worn on the skin and replaced at intervals. One of skill in the art is aware of patch systems for drug delivery suitable for this purpose. It is of note that transdermal administration is especially amenable to uninterrupted administration, as exchange of a first exhausted patch can advantageously be accomplished simultaneously with the placement of a new, second patch, for example on the surface of the skin immediately adjacent to the first exhausted patch and immediately prior to removal of the first exhausted patch. Issues of flow interruption or power cell failure do not arise.
The inventive compositions may further comprise a pharmaceutically acceptable carrier. Examples of suitable pharmaceutical carriers are well known in the art and include solutions, e.g. phosphate buffered saline solutions, water, emulsions, such as oil/water emulsions, various types of wetting agents, sterile solutions, liposomes, etc. Compositions comprising such carriers can be formulated by well known conventional methods. Formulations can comprise carbohydrates, buffer solutions, amino acids and/or surfactants. Carbohydrates may be non-reducing sugars, preferably trehalose, sucrose, octasulfate, sorbitol or xylitol. In general, as used herein, “pharmaceutically acceptable carrier” means any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed and include: additional buffering agents; preservatives; co-solvents; antioxidants, including ascorbic acid and methionine; chelating agents such as EDTA; metal complexes (e.g., Zn-protein complexes); biodegradable polymers, such as polyesters; salt-forming counter-ions, such as sodium, polyhydric sugar alcohols; amino acids, such as alanine, glycine, asparagine, 2-phenylalanine, and threonine; sugars or sugar alcohols, such as trehalose, sucrose, octasulfate, sorbitol or xylitol stachyose, mannose, sorbose, xylose, ribose, myoinisitose, galactose, lactitol, ribitol, myoinisitol, galactitol, glycerol, cyclitols (e.g., inositol), polyethylene glycol; sulfur containing reducing agents, such as glutathione, thioctic acid, sodium thioglycolate, thioglycerol, [alpha]-monothioglycerol, and sodium thio sulfate; low molecular weight proteins, such as human serum albumin, bovine serum albumin, gelatin, or other immunoglobulins; and hydrophilic polymers, such as polyvinylpyrrolidone. Such formulations may be used for continuous administrations which may be intravenous or subcutaneous with and/or without pump systems. Amino acids may be charged amino acids, preferably lysine, lysine acetate, arginine, glutamate and/or histidine. Surfactants may be detergents, preferably with a molecular weight of >1.2 KD and/or a polyether, preferably with a molecular weight of >3 KD. Non-limiting examples for preferred detergents are Tween 20, Tween 40, Tween 60, Tween 80 or Tween 85. Non-limiting examples for preferred polyethers are PEG 3000, PEG 3350, PEG 4000 or PEG 5000. Buffer systems used in the present invention can have a preferred pH of 5-9 and may comprise citrate, succinate, phosphate, histidine and acetate.
The compositions of the present invention can be administered to the subject at a suitable dose which can be determined e.g. by dose escalating studies by administration of increasing doses of the polypeptide of the invention exhibiting cross-species specificity described herein to non-chimpanzee primates, for instance macaques. As set forth above, the antibody or antigen binding fragment thereof or antibody construct of the invention exhibiting cross-species specificity described herein can be advantageously used in identical form in preclinical testing in non-chimpanzee primates and as drug in humans. These compositions can also be administered in combination with other proteinaceous and non-proteinaceous drugs. These drugs may be administered simultaneously with the composition comprising the polypeptide of the invention as defined herein or separately before or after administration of said polypeptide in timely defined intervals and doses. The dosage regimen will be determined by the attending physician and clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently.
Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, inert gases and the like. In addition, the composition of the present invention might comprise proteinaceous carriers, like, e.g., serum albumin or immunoglobulin, preferably of human origin. It is envisaged that the composition of the invention might comprise, in addition to the polypeptide of the invention defined herein, further biologically active agents, depending on the intended use of the composition. Such agents might be drugs acting on the gastro-intestinal system, drugs acting as cytostatica, drugs preventing hyperurikemia, drugs inhibiting immunoreactions (e.g. corticosteroids), drugs modulating the inflammatory response, drugs acting on the circulatory system and/or agents such as cytokines known in the art. It is also envisaged that the antibody or antigen binding fragment thereof or antibody construct of the present invention is applied in a co-therapy, i.e., in combination with another anti-cancer medicament.
The biological activity of the pharmaceutical composition defined herein can be determined for instance by cytotoxicity assays, as described in the following examples, in WO 99/54440 or by Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12). “Efficacy” or “in vivo efficacy” as used herein refers to the response to therapy by the pharmaceutical composition of the invention, using e.g. standardized NCI response criteria. The success or in vivo efficacy of the therapy using a pharmaceutical composition of the invention refers to the effectiveness of the composition for its intended purpose, i.e. the ability of the composition to cause its desired effect, i.e. depletion of pathologic cells, e.g. tumor cells. The in vivo efficacy may be monitored by established standard methods for the respective disease entities including, but not limited to white blood cell counts, differentials, Fluorescence Activated Cell Sorting, bone marrow aspiration. In addition, various disease specific clinical chemistry parameters and other established standard methods may be used. Furthermore, computer-aided tomography, X-ray, nuclear magnetic resonance tomography (e.g. for National Cancer Institute-criteria based response assessment [Cheson B D, Horning S J, Coiffier B, Shipp M A, Fisher R I, Connors J M, Lister T A, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris N L, Armitage J O, Carter W, Hoppe R, Canellos G P. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 April; 17(4):1244]), positron-emission tomography scanning, white blood cell counts, differentials, Fluorescence Activated Cell Sorting, bone marrow aspiration, lymph node biopsies/histologies, and various lymphoma specific clinical chemistry parameters (e.g. lactate dehydrogenase) and other established standard methods may be used.
Another major challenge in the development of drugs such as the pharmaceutical composition of the invention is the predictable modulation of pharmacokinetic properties. To this end, a pharmacokinetic profile of the drug candidate, i.e. a profile of the pharmacokinetic parameters that affect the ability of a particular drug to treat a given condition, can be established. Pharmacokinetic parameters of the drug influencing the ability of a drug for treating a certain disease entity include, but are not limited to: half-life, volume of distribution, hepatic first-pass metabolism and the degree of blood serum binding. The efficacy of a given drug agent can be influenced by each of the parameters mentioned above.
“Half-life” means the time where 50% of an administered drug are eliminated through biological processes, e.g. metabolism, excretion, etc.
By “hepatic first-pass metabolism” is meant the propensity of a drug to be metabolized upon first contact with the liver, i.e. during its first pass through the liver.
“Volume of distribution” means the degree of retention of a drug throughout the various compartments of the body, like e.g. intracellular and extracellular spaces, tissues and organs, etc. and the distribution of the drug within these compartments.
“Degree of blood serum binding” means the propensity of a drug to interact with and bind to blood serum proteins, such as albumin, leading to a reduction or loss of biological activity of the drug.
Pharmacokinetic parameters also include bioavailability, lag time (Tlag), Tmax, absorption rates, more onset and/or Cmax for a given amount of drug administered. “Bioavailability” means the amount of a drug in the blood compartment. “Lag time” means the time delay between the administration of the drug and its detection and measurability in blood or plasma.
“Tmax” is the time after which maximal blood concentration of the drug is reached, and “Cmax” is the blood concentration maximally obtained with a given drug. The time to reach a blood or tissue concentration of the drug which is required for its biological effect is influenced by all parameters. Pharmacokinetic parameters of bispecific single chain antibodies exhibiting cross-species specificity, which may be determined in preclinical animal testing in non-chimpanzee primates as outlined above, are also set forth e.g. in the publication by Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12).
The term “toxicity” as used herein refers to the toxic effects of a drug manifested in adverse events or severe adverse events. These side events might refer to a lack of tolerability of the drug in general and/or a lack of local tolerance after administration. Toxicity could also include teratogenic or carcinogenic effects caused by the drug.
The term “safety”, “in vivo safety” or “tolerability” as used herein defines the administration of a drug without inducing severe adverse events directly after administration (local tolerance) and during a longer period of application of the drug. “Safety”, “in vivo safety” or “tolerability” can be evaluated e.g. at regular intervals during the treatment and follow-up period. Measurements include clinical evaluation, e.g. organ manifestations, and screening of laboratory abnormalities. Clinical evaluation may be carried out and deviations to normal findings recorded/coded according to NCI-CTC and/or MedDRA standards. Organ manifestations may include criteria such as allergy/immunology, blood/bone marrow, cardiac arrhythmia, coagulation and the like, as set forth e.g. in the Common Terminology Criteria for adverse events v3.0 (CTCAE). Laboratory parameters which may be tested include for instance hematology, clinical chemistry, coagulation profile and urine analysis and examination of other body fluids such as serum, plasma, lymphoid or spinal fluid, liquor and the like. Safety can thus be assessed e.g. by physical examination, imaging techniques (i.e. ultrasound, x-ray, CT scans, Magnetic Resonance Imaging (MRI), other measures with technical devices (i.e. electrocardiogram), vital signs, by measuring laboratory parameters and recording adverse events. For example, adverse events in non-chimpanzee primates in the uses and methods according to the invention may be examined by histopathological and/or histochemical methods.
The term “effective dose” or “effective dosage” is defined as an amount sufficient to achieve or at least partially achieve the desired effect. The term “therapeutically effective dose” is defined as an amount sufficient to cure or at least partially arrest the disease and its complications in a patient already suffering from the disease. Amounts effective for this use will depend upon the severity of the infection and the general state of the subject's own immune system. The term “patient” includes human and other mammalian subjects that receive either prophylactic or therapeutic treatment.
The term “effective and non-toxic dose” as used herein refers to a tolerable dose of an inventive antibody or antigen binding fragment thereof or antibody construct which is high enough to cause depletion of pathologic cells, tumor elimination, tumor shrinkage or stabilization of disease without or essentially without major toxic effects. Such effective and non-toxic doses may be determined e.g. by dose escalation studies described in the art and should be below the dose inducing severe adverse side events (dose limiting toxicity, DLT).
The above terms are also referred to e.g. in the Preclinical safety evaluation of biotechnology-derived pharmaceuticals S6; ICH Harmonised Tripartite Guideline; ICH Steering Committee meeting on Jul. 16, 1997.
The appropriate dosage, or therapeutically effective amount, of the antibody or antigen binding fragment thereof or antibody construct of the invention will depend on the condition to be treated, the severity of the condition, prior therapy, and the patient's clinical history and response to the therapeutic agent. The proper dose can be adjusted according to the judgment of the attending physician such that it can be administered to the patient one time or over a series of administrations. The pharmaceutical composition can be administered as a sole therapeutic or in combination with additional therapies such as anti-cancer therapies as needed.
The pharmaceutical compositions of this invention are particularly useful for parenteral administration, i.e., subcutaneously, intramuscularly, intravenously, intra-articular and/or intra-synovial. Parenteral administration can be by bolus injection or continuous infusion.
If the pharmaceutical composition has been lyophilized, the lyophilized material is first reconstituted in an appropriate liquid prior to administration. The lyophilized material may be reconstituted in, e.g., bacteriostatic water for injection (BWFI), physiological saline, phosphate buffered saline (PBS), or the same formulation the protein had been in prior to lyophilization.
In an internal analysis of proprietary mRNA expression data it has been surprisingly found that CDH19 expression is elevated in both primary and metastatic melanoma tumors compared to normal, untransformed tissues. Internal analysis also confirmed that expression of CDH19 in normal tissues is limited to neural crest derived peripheral nerve ganglia and nerve fibers. The differential CDH19 expression in normal and tumor tissues makes this protein attractive for cell-surface targeting therapeutics. Although CDH 19 was discussed as one marker as part of long lists of markers associated with some cancer types (see e.g. WO2009/055937) or Parkinson's disease (see e.g. WO2005/067391) CDH19 was never discussed as a prognostic marker or a drug target in connection with melanoma tumors.
As stated above, the present invention provides an isolated human antibody or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell. In a preferred embodiment the antibody or antigen binding fragment thereof comprises a monoclonal antibody or a fragment thereof.
The “CDH19 extracellular domain” or “CDH19 ECD” refers to a form of CDH19 which is essentially free of transmembrane and cytoplasmic domains of CDH19. It will be understood by the skilled artisan that the transmembrane domain identified for the CDH19 polypeptide of the present invention is identified pursuant to criteria routinely employed in the art for identifying that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain specifically mentioned herein. A preferred human CDH19 ECD is shown in SEQ ID NO: 948 (aa residues 44-596). In this context it is understood that the CDH19 ECD represents the part of CDH19 on the surface of a target cell.
The affinity of the antibody or fragment thereof for human CDH19 is preferably ≤15 nM, more preferably ≤10 nM, even more preferably ≤5 nM, even more preferably ≤1 nM, even more preferably ≤0.5 nM, even more preferably ≤0.1 nM, and most preferably ≤0.05 nM. The affinity of the first binding domain for macaque CDH19 is preferably ≤15 nM, more preferably ≤10 nM, even more preferably ≤5 nM, even more preferably ≤1 nM, even more preferably ≤0.5 nM, even more preferably ≤0.1 nM, and most preferably ≤0.05 nM or even ≤0.01 nM. The affinity can be measured for example in a Biacore assay or in a Scatchard assay, e.g. as described in the Examples. The affinity gap for binding to macaque CDH19 versus human CDH19 is preferably [1:10-1:5] or [5:1-10:1], more preferably [1:5-5:1], and most preferably [1:2-3:1] or even [1:1-3:1]. Other methods of determining the affinity are well-known to the skilled person.
Human antibodies avoid some of the problems associated with antibodies that possess murine or rat variable and/or constant regions. The presence of such murine or rat derived proteins can lead to the rapid clearance of the antibodies or can lead to the generation of an immune response against the antibody by a patient. In order to avoid the utilization of murine or rat derived antibodies, human or fully human antibodies can be generated through the introduction of human antibody function into a rodent so that the rodent produces fully human antibodies.
The ability to clone and reconstruct megabase-sized human loci in YACs and to introduce them into the mouse germline provides a powerful approach to elucidating the functional components of very large or crudely mapped loci as well as generating useful models of human disease. Furthermore, the utilization of such technology for substitution of mouse loci with their human equivalents could provide unique insights into the expression and regulation of human gene products during development, their communication with other systems, and their involvement in disease induction and progression.
An important practical application of such a strategy is the “humanization” of the mouse humoral immune system. Introduction of human immunoglobulin (Ig) loci into mice in which the endogenous Ig genes have been inactivated offers the opportunity to study the mechanisms underlying programmed expression and assembly of antibodies as well as their role in B-cell development. Furthermore, such a strategy could provide an ideal source for production of fully human monoclonal antibodies (mAbs)—an important milestone towards fulfilling the promise of antibody therapy in human disease. Fully human antibodies are expected to minimize the immunogenic and allergic responses intrinsic to mouse or mouse-derivatized mAbs and thus to increase the efficacy and safety of the administered antibodies. The use of fully human antibodies can be expected to provide a substantial advantage in the treatment of chronic and recurring human diseases, such as inflammation, autoimmunity, and cancer, which require repeated antibody administrations.
One approach towards this goal was to engineer mouse strains deficient in mouse antibody production with large fragments of the human Ig loci in anticipation that such mice would produce a large repertoire of human antibodies in the absence of mouse antibodies. Large human Ig fragments would preserve the large variable gene diversity as well as the proper regulation of antibody production and expression. By exploiting the mouse machinery for antibody diversification and selection and the lack of immunological tolerance to human proteins, the reproduced human antibody repertoire in these mouse strains should yield high affinity antibodies against any antigen of interest, including human antigens. Using the hybridoma technology, antigen-specific human mAbs with the desired specificity could be readily produced and selected. This general strategy was demonstrated in connection with our generation of the first XenoMouse mouse strains, as published in 1994. (See Green et al. Nature Genetics 7:13-21 (1994)) The XenoMouse strains were engineered with yeast artificial chromosomes (YACs) containing 245 kb and 190 kb-sized germline configuration fragments of the human heavy chain locus and kappa light chain locus, respectively, which contained core variable and constant region sequences. Id. The human Ig containing YACs proved to be compatible with the mouse system for both rearrangement and expression of antibodies and were capable of substituting for the inactivated mouse Ig genes. This was demonstrated by their ability to induce B-cell development, to produce an adult-like human repertoire of fully human antibodies, and to generate antigen-specific human mAbs. These results also suggested that introduction of larger portions of the human Ig loci containing greater numbers of V genes, additional regulatory elements, and human Ig constant regions might recapitulate substantially the full repertoire that is characteristic of the human humoral response to infection and immunization. The work of Green et al. was recently extended to the introduction of greater than approximately 80% of the human antibody repertoire through introduction of megabase sized, germline configuration YAC fragments of the human heavy chain loci and kappa light chain loci, respectively. See Mendez et al. Nature Genetics 15:146-156 (1997) and U.S. patent application Ser. No. 08/759,620, filed Dec. 3, 1996, the disclosures of which are hereby incorporated by reference.
The production of the XenoMouse mice is further discussed and delineated in U.S. patent application Ser. No. 07/466,008, filed Jan. 12, 1990, Ser. No. 07/610,515, filed Nov. 8, 1990, Ser. No. 07/919,297, filed Jul. 24, 1992, Ser. No. 07/922,649, filed Jul. 30, 1992, filed Ser. No. 08/031,801, filed Mar. 15, 1993, Ser. No. 08/112,848, filed Aug. 27, 1993, Ser. No. 08/234,145, filed Apr. 28, 1994, Ser. No. 08/376,279, filed Jan. 20, 1995, Ser. No. 08/430,938, Apr. 27, 1995, Ser. No. 08/464,584, filed Jun. 5, 1995, Ser. No. 08/464,582, filed Jun. 5, 1995, Ser. No. 08/463,191, filed Jun. 5, 1995, Ser. No. 08/462,837, filed Jun. 5, 1995, Ser. No. 08/486,853, filed Jun. 5, 1995, Ser. No. 08/486,857, filed Jun. 5, 1995, Ser. No. 08/486,859, filed Jun. 5, 1995, Ser. No. 08/462,513, filed Jun. 5, 1995, Ser. No. 08/724,752, filed Oct. 2, 1996, and Ser. No. 08/759,620, filed Dec. 3, 1996 and U.S. Pat. Nos. 6,162,963, 6,150,584, 6,114,598, 6,075,181, and 5,939,598 and Japanese Patent Nos. 3 068 180 B2, 3 068 506 B2, and 3 068 507 B2. See also Mendez et al. Nature Genetics 15:146-156 (1997) and Green and Jakobovits J. Exp. Med. 188:483-495 (1998). See also European Patent No., EP 0 463151 B1, grant published Jun. 12, 1996, International Patent Application No., WO 94/02602, published Feb. 3, 1994, International Patent Application No., WO 96/34096, published Oct. 31, 1996, WO 98/24893, published Jun. 11, 1998, WO 00/76310, published Dec. 21, 2000, WO 03/47336. The disclosures of each of the above-cited patents, applications, and references are hereby incorporated by reference in their entirety.
In an alternative approach, others, including GenPharm International, Inc., have utilized a “minilocus” approach. In the minilocus approach, an exogenous Ig locus is mimicked through the inclusion of pieces (individual genes) from the Ig locus. Thus, one or more V.sub.H genes, one or more D.sub.H genes, one or more J.sub.H genes, a mu constant region, and a second constant region (preferably a gamma constant region) are formed into a construct for insertion into an animal. This approach is described in U.S. Pat. No. 5,545,807 to Surani et al. and U.S. Pat. Nos. 5,545,806, 5,625,825, 5,625,126, 5,633,425, 5,661,016, 5,770,429, 5,789,650, 5,814,318, 5,877,397, 5,874,299, and 6,255,458 each to Lonberg and Kay, U.S. Pat. Nos. 5,591,669 and 6,023.010 to Krimpenfort and Berns, U.S. Pat. Nos. 5,612,205, 5,721,367, and 5,789,215 to Berns et al., and U.S. Pat. No. 5,643,763 to Choi and Dunn, and GenPharm International U.S. patent application Ser. No. 07/574,748, filed Aug. 29, 1990, Ser. No. 07/575,962, filed Aug. 31, 1990, Ser. No. 07/810,279, filed Dec. 17, 1991, Ser. No. 07/853,408, filed Mar. 18, 1992, Ser. No. 07/904,068, filed Jun. 23, 1992, Ser. No. 07/990,860, filed Dec. 16, 1992, Ser. No. 08/053,131, filed Apr. 26, 1993, Ser. No. 08/096,762, filed Jul. 22, 1993, Ser. No. 08/155,301, filed Nov. 18, 1993, Ser. No. 08/161,739, filed Dec. 3, 1993, Ser. No. 08/165,699, filed Dec. 10, 1993, Ser. No. 08/209,741, filed Mar. 9, 1994, the disclosures of which are hereby incorporated by reference. See also European Patent No. 0 546 073 B 1, International Patent Application Nos. WO 92/03918, WO 92/22645, WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO 96/14436, WO 97/13852, and WO 98/24884 and U.S. Pat. No. 5,981,175, the disclosures of which are hereby incorporated by reference in their entirety. See further Taylor et al., 1992, Chen et al., 1993, Tuaillon et al., 1993, Choi et al., 1993, Lonberg et al., (1994), Taylor et al., (1994), and Tuaillon et al., (1995), Fishwild et al., (1996), the disclosures of which are hereby incorporated by reference in their entirety.
Kirin has also demonstrated the generation of human antibodies from mice in which, through microcell fusion, large pieces of chromosomes, or entire chromosomes, have been introduced. See European Patent Application Nos. 773 288 and 843 961, the disclosures of which are hereby incorporated by reference. Xenerex Biosciences is developing a technology for the potential generation of human antibodies. In this technology, SCID mice are reconstituted with human lymphatic cells, e.g., B and/or T cells. Mice are then immunized with an antigen and can generate an immune response against the antigen. See U.S. Pat. Nos. 5,476,996, 5,698,767, and 5,958,765.
Human anti-mouse antibody (HAMA) responses have led the industry to prepare chimeric or otherwise humanized antibodies. While chimeric antibodies have a human constant region and a murine variable region, it is expected that certain human anti-chimeric antibody (HACA) responses will be observed, particularly in chronic or multi-dose utilizations of the antibody. Thus, it would be desirable to provide fully human antibodies against EGFRvIII in order to vitiate concerns and/or effects of HAMA or HACA response.
According to one embodiment the antibody of the present invention is a dimer comprising two fusion proteins created by fusing a CDH19 binding fragment of a CDH19 antibody to the Fc region of an antibody. The dimer can be made by, for example, inserting a gene fusion encoding the fusion protein into an appropriate expression vector, expressing the gene fusion in host cells transformed with the recombinant expression vector, and allowing the expressed fusion protein to assemble much like antibody molecules, whereupon interchain disulfide bonds form between the Fc moieties to yield the dimer.
The term “Fc polypeptide” as used herein includes native and mutein forms of polypeptides derived from the Fc region of an antibody. Truncated forms of such polypeptides containing the hinge region that promotes dimerization also are included. Fusion proteins comprising Fc moieties (and oligomers formed therefrom) offer the advantage of facile purification by affinity chromatography over Protein A or Protein G columns.
One suitable Fc polypeptide, described in PCT application WO 93/10151 (hereby incorporated by reference), is a single chain polypeptide extending from the N-terminal hinge region to the native C-terminus of the Fc region of a human IgG antibody. Another useful Fc polypeptide is the Fc mutein described in U.S. Pat. No. 5,457,035 and in Baum et al., 1994, EMBO J. 13:3992-4001. The amino acid sequence of this mutein is identical to that of the native Fc sequence presented in WO 93/10151, except that amino acid 19 has been changed from Leu to Ala, amino acid 20 has been changed from Leu to Glu, and amino acid 22 has been changed from Gly to Ala. The mutein exhibits reduced affinity for Fc receptors.
Alternatively, the antibody of the invention is a fusion protein comprising multiple CDH19 antibody polypeptides, with or without peptide linkers (spacer peptides). Among the suitable peptide linkers are those described in U.S. Pat. Nos. 4,751,180 and 4,935,233 or WO 88/09344.
Another method for preparing oligomeric CDH19 antibody derivatives involves use of a leucine zipper. Leucine zipper domains are peptides that promote oligomerization of the proteins in which they are found. Leucine zippers were originally identified in several DNA-binding proteins (Landschulz et al., 1988, Science 240:1759), and have since been found in a variety of different proteins. Among the known leucine zippers are naturally occurring peptides and derivatives thereof that dimerize or trimerize. Examples of leucine zipper domains suitable for producing soluble oligomeric proteins are described in PCT application WO 94/10308, and the leucine zipper derived from lung surfactant protein D (SPD) described in Hoppe et al., 1994, FEBS Letters 344:191, hereby incorporated by reference. The use of a modified leucine zipper that allows for stable trimerization of a heterologous protein fused thereto is described in Fanslow et al., 1994, Semin. Immunol. 6:267-78. In one approach, recombinant fusion proteins comprising CDH19 antibody fragment or derivative fused to a leucine zipper peptide are expressed in suitable host cells, and the soluble oligomeric CDH19 antibody fragments or derivatives that form are recovered from the culture supernatant.
Covalent modifications of antigen binding proteins are included within the scope of this invention, and are generally, but not always, done post-translationally. For example, several types of covalent modifications of the antigen binding protein are introduced into the molecule by reacting specific amino acid residues of the antigen binding protein with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C-terminal residues.
Cysteinyl residues most commonly are reacted with α-haloacetates (and corresponding amines), such as chloroacetic acid or chloroacetamide, to give carboxymethyl or carboxyamidomethyl derivatives. Cysteinyl residues also are derivatized by reaction with bromotrifluoroacetone, α-bromo-β-(5-imidozoyl)propionic acid, chloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl 2-pyridyl disulfide, p-chloromercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa-1,3-diazole.
Histidyl residues are derivatized by reaction with diethylpyrocarbonate at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain. Para-bromophenacyl bromide also is useful; the reaction is preferably performed in 0.1 M sodium cacodylate at pH 6.0.
Lysinyl and amino terminal residues are reacted with succinic or other carboxylic acid anhydrides. Derivatization with these agents has the effect of reversing the charge of the lysinyl residues. Other suitable reagents for derivatizing alpha-amino-containing residues include imidoesters such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea; 2,4-pentanedione; and transaminase-catalyzed reaction with glyoxylate.
Arginyl residues are modified by reaction with one or several conventional reagents, among them phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin. Derivatization of arginine residues requires that the reaction be performed in alkaline conditions because of the high pKa of the guanidine functional group. Furthermore, these reagents may react with the groups of lysine as well as the arginine epsilon-amino group.
The specific modification of tyrosyl residues may be made, with particular interest in introducing spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. Most commonly, N-acetylimidizole and tetranitromethane are used to form O-acetyl tyrosyl species and 3-nitro derivatives, respectively. Tyrosyl residues are iodinated using ¹²⁵I or ¹³¹I to prepare labeled proteins for use in radioimmunoassay, the chloramine T method described above being suitable.
Carboxyl side groups (aspartyl or glutamyl) are selectively modified by reaction with carbodiimides (R′—N═C═N—R′), where R and R′ are optionally different alkyl groups, such as 1-cyclohexyl-3-(2-morpholinyl-4-ethyl) carbodiimide or 1-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide. Furthermore, aspartyl and glutamyl residues are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.
Derivatization with bifunctional agents is useful for crosslinking antigen binding proteins to a water-insoluble support matrix or surface for use in a variety of methods. Commonly used crosslinking agents include, e.g., 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3′-dithiobis(succinimidylpropionate), and bifunctional maleimides such as bis-N-maleimido-1,8-octane. Derivatizing agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate yield photoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbohydrates and the reactive substrates described in U.S. Pat. Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440 are employed for protein immobilization.
Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues, respectively. Alternatively, these residues are deamidated under mildly acidic conditions. Either form of these residues falls within the scope of this invention.
Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the α-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, 1983, pp. 79-86), acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.
Another type of covalent modification of the antigen binding protein included within the scope of this invention comprises altering the glycosylation pattern of the protein. As is known in the art, glycosylation patterns can depend on both the sequence of the protein (e.g., the presence or absence of particular glycosylation amino acid residues, discussed below), or the host cell or organism in which the protein is produced. Particular expression systems are discussed below.
Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tri-peptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tri-peptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose, to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
Addition of glycosylation sites to the antigen binding protein is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tri-peptide sequences (for N-linked glycosylation sites). The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the starting sequence (for O-linked glycosylation sites). For ease, the antigen binding protein amino acid sequence is preferably altered through changes at the DNA level, particularly by mutating the DNA encoding the target polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
Another means of increasing the number of carbohydrate moieties on the antigen binding protein is by chemical or enzymatic coupling of glycosides to the protein. These procedures are advantageous in that they do not require production of the protein in a host cell that has glycosylation capabilities for N- and O-linked glycosylation. Depending on the coupling mode used, the sugar(s) may be attached to (a) arginine and histidine, (b) free carboxyl groups, (c) free sulfhydryl groups such as those of cysteine, (d) free hydroxyl groups such as those of serine, threonine, or hydroxyproline, (e) aromatic residues such as those of phenylalanine, tyrosine, or tryptophan, or (f) the amide group of glutamine. These methods are described in WO 87/05330 published Sep. 11, 1987, and in Aplin and Wriston, 1981, CRC Crit. Rev. Biochem., pp. 259-306.
Removal of carbohydrate moieties present on the starting antigen binding protein may be accomplished chemically or enzymatically. Chemical deglycosylation requires exposure of the protein to the compound trifluoromethanesulfonic acid, or an equivalent compound. This treatment results in the cleavage of most or all sugars except the linking sugar (N-acetylglucosamine or N-acetylgalactosamine), while leaving the polypeptide intact. Chemical deglycosylation is described by Hakimuddin et al., 1987, Arch. Biochem. Biophys. 259:52 and by Edge et al., 1981, Anal. Biochem. 118:131. Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases as described by Thotakura et al., 1987, Meth. Enzymol. 138:350. Glycosylation at potential glycosylation sites may be prevented by the use of the compound tunicamycin as described by Duskin et al., 1982, J. Biol. Chem. 257:3105. Tunicamycin blocks the formation of protein-N-glycoside linkages.
Another type of covalent modification of the antigen binding protein comprises linking the antigen binding protein to various non-proteinaceous polymers, including, but not limited to, various polyols such as polyethylene glycol, polypropylene glycol or polyoxyalkylenes, in the manner set forth in U.S. Pat. Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337. In addition, as is known in the art, amino acid substitutions may be made in various positions within the antigen binding protein to facilitate the addition of polymers such as PEG.
In some embodiments, the covalent modification of the antigen binding proteins of the invention comprises the addition of one or more labels.
The term “labelling group” means any detectable label. Examples of suitable labelling groups include, but are not limited to, the following: radioisotopes or radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I), fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphors), enzymatic groups (e.g., horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase), chemiluminescent groups, biotinyl groups, or predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, the labelling group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labelling proteins are known in the art and may be used in performing the present invention.
In general, labels fall into a variety of classes, depending on the assay in which they are to be detected: a) isotopic labels, which may be radioactive or heavy isotopes; b) magnetic labels (e.g., magnetic particles); c) redox active moieties; d) optical dyes; enzymatic groups (e.g. horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase); e) biotinylated groups; and f) predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags, etc.). In some embodiments, the labelling group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labelling proteins are known in the art and may be used in performing the present invention.
Specific labels include optical dyes, including, but not limited to, chromophores, phosphors and fluorophores, with the latter being specific in many instances. Fluorophores can be either “small molecule” fluores, or proteinaceous fluores.
By “fluorescent label” is meant any molecule that may be detected via its inherent fluorescent properties. Suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin, methyl-coumarins, pyrene, Malacite green, stilbene, Lucifer Yellow, Cascade BlueJ, Texas Red, IAEDANS, EDANS, BODIPY FL, LC Red 640, Cy 5, Cy 5.5, LC Red 705, Oregon green, the Alexa-Fluor dyes (Alexa Fluor 350, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660, Alexa Fluor 680), Cascade Blue, Cascade Yellow and R-phycoerythrin (PE) (Molecular Probes, Eugene, Oreg.), FITC, Rhodamine, and Texas Red (Pierce, Rockford, Ill.), Cy5, Cy5.5, Cy7 (Amersham Life Science, Pittsburgh, Pa.). Suitable optical dyes, including fluorophores, are described in Molecular Probes Handbook by Richard P. Haugland, hereby expressly incorporated by reference.
Suitable proteinaceous fluorescent labels also include, but are not limited to, green fluorescent protein, including a Renilla, Ptilosarcus, or Aequorea species of GFP (Chalfie et al., 1994, Science 263:802-805), EGFP (Clontech Laboratories, Inc., Genbank Accession Number U55762), blue fluorescent protein (BFP, Quantum Biotechnologies, Inc. 1801 de Maisonneuve Blvd. West, 8th Floor, Montreal, Quebec, Canada H3H 1J9; Stauber, 1998, Biotechniques 24:462-471; Heim et al., 1996, Curr. Biol. 6:178-182), enhanced yellow fluorescent protein (EYFP, Clontech Laboratories, Inc.), luciferase (Ichiki et al., 1993, J. Immunol. 150:5408-5417), β galactosidase (Nolan et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:2603-2607) and Renilla (WO92/15673, WO95/07463, WO98/14605, WO98/26277, WO99/49019, U.S. Pat. Nos. 5,292,658, 5,418,155, 5,683,888, 5,741,668, 5,777,079, 5,804,387, 5,874,304, 5,876,995, 5,925,558). All of the above-cited references are expressly incorporated herein by reference.
As described in appended example 2 a broad number of CDH19 specific binder has been characterized with respect to identified binding characteristics and those binders were grouped into five different bins, which refers to five different subgroups of CDH19 specific binding domains. Accordingly, in one embodiment the human antibody or antigen binding fragment thereof of the invention comprises a human binding domain or antigen binding fragment thereof comprising a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:

(a) CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 222, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 252, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926, and CDR-H1 as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID NO: 904, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926; which all characterize binding domains for CDH19 grouped into bin 1;
(b) CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 126, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 300, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 306, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 312, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 928, CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 929, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 942, CDR-H1 as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 943, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 937, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 919, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 936, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 933, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 917, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 934, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 930, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 931, and
CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 932; which all characterize binding domains for CDH19 grouped into bin 2;
(c) CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 96, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 102, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID NO: 156, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 912, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 913, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 910, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 911, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 914, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, and
CDR-H1 as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID NO: 920, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324; which all characterize binding domains for CDH19 grouped into bin 3;
(d) CDR-H1 as depicted in SEQ ID NO: 4, CDR-H2 as depicted in SEQ ID NO: 5, CDR-H3 as depicted in SEQ ID NO: 6, CDR-L1 as depicted in SEQ ID NO: 172, CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3 as depicted in SEQ ID NO: 174, CDR-H1 as depicted in SEQ ID NO: 10, CDR-H2 as depicted in SEQ ID NO: 11, CDR-H3 as depicted in SEQ ID NO: 12, CDR-L1 as depicted in SEQ ID NO: 178, CDR-L2 as depicted in SEQ ID NO: 179 and CDR-L3 as depicted in SEQ ID NO: 180, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 198, CDR-H1 as depicted in SEQ ID NO: 34, CDR-H2 as depicted in SEQ ID NO: 35, CDR-H3 as depicted in SEQ ID NO: 36, CDR-L1 as depicted in SEQ ID NO: 202, CDR-L2 as depicted in SEQ ID NO: 203 and CDR-L3 as depicted in SEQ ID NO: 204, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 214, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 59, CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 64, CDR-H2 as depicted in SEQ ID NO: 65, CDR-H3 as depicted in SEQ ID NO: 66, CDR-L1 as depicted in SEQ ID NO: 232, CDR-L2 as depicted in SEQ ID NO: 233 and CDR-L3 as depicted in SEQ ID NO: 234, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 71, CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 328, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 902, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 903, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID NO: 925, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID NO: 908, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID NO: 906, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 921, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 940, CDR-H1 as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID NO: 941, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, and
CDR-H1 as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330; which all characterize binding domains for CDH19 grouped into bin 4; and
(e) CDR-H1 as depicted in SEQ ID NO: 76, CDR-H2 as depicted in SEQ ID NO: 77, CDR-H3 as depicted in SEQ ID NO: 78, CDR-L1 as depicted in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245 and CDR-L3 as depicted in SEQ ID NO: 246, CDR-H1 as depicted in SEQ ID NO: 88, CDR-H2 as depicted in SEQ ID NO: 89, CDR-H3 as depicted in SEQ ID NO: 90, CDR-L1 as depicted in SEQ ID NO: 256, CDR-L2 as depicted in SEQ ID NO: 257 and CDR-L3 as depicted in SEQ ID NO: 258, CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276, CDR-H1 as depicted in SEQ ID NO: 112, CDR-H2 as depicted in SEQ ID NO: 113, CDR-H3 as depicted in SEQ ID NO: 114, CDR-L1 as depicted in SEQ ID NO: 280, CDR-L2 as depicted in SEQ ID NO: 281 and CDR-L3 as depicted in SEQ ID NO: 282, and
CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276 which all characterize binding domains for CDH19 grouped into bin 5;

(a) as depicted in SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, and SEQ ID NO: 495;
- which all characterize binding domains for CDH19 grouped into bin 1;
(b) as depicted in SEQ ID NO: 342, SEQ ID NO: 366, SEQ ID NO: 370, SEQ ID NO: 344, SEQ ID NO: 372, SEQ ID NO: 368, SEQ ID NO: 496, SEQ ID NO: 497, SEQ ID NO: 498, SEQ ID NO: 499, SEQ ID NO: 500, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO: 510, SEQ ID NO: 511, SEQ ID NO: 512, SEQ ID NO: 519, SEQ ID NO: 520, SEQ ID NO: 521, SEQ ID NO: 522, SEQ ID NO: 523, SEQ ID NO: 524, SEQ ID NO: 525, SEQ ID NO: 526, SEQ ID NO: 527, SEQ ID NO: 528, SEQ ID NO: 529, SEQ ID NO: 530, SEQ ID NO: 531, SEQ ID NO: 532, SEQ ID NO: 533, SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 536, SEQ ID NO: 537, and SEQ ID NO: 538;
- which all characterize binding domains for CDH19 grouped into bin 2;
(c) as depicted in SEQ ID NO: 338, SEQ ID NO: 354, SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484, SEQ ID NO: 501, SEQ ID NO: 502, SEQ ID NO: 503, SEQ ID NO: 504, SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 517, and SEQ ID NO: 518;
- which all characterize binding domains for CDH19 grouped into bin 3;
(d) as depicted in SEQ ID NO: 352, SEQ ID NO: 360, SEQ ID NO: 388, SEQ ID NO: 386, SEQ ID NO: 340, SEQ ID NO: 346, SEQ ID NO: 374, SEQ ID NO: 348, SEQ ID NO: 390, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466, SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472, SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490, SEQ ID NO: 491, SEQ ID NO: 513, SEQ ID NO: 514, SEQ ID NO: 515, SEQ ID NO: 516, SEQ ID NO: 540, SEQ ID NO: 541, SEQ ID NO: 542, and SEQ ID NO: 543;
- which all characterize binding domains for CDH19 grouped into bin 4; and
(e) as depicted in SEQ ID NO: 376, SEQ ID NO: 392, SEQ ID NO: 358, SEQ ID NO: 350, and SEQ ID NO: 507;
- which all characterize binding domains for CDH19 grouped into bin 5.

(a) as depicted in SEQ ID NO: 418, SEQ ID NO: 420, SEQ ID NO: 580, SEQ ID NO: 581, SEQ ID NO: 582, SEQ ID NO: 587, SEQ ID NO: 588, SEQ ID NO: 589, and SEQ ID NO: 590;
- which all characterize binding domains for CDH19 grouped into bin 1;
(b) as depicted in SEQ ID NO: 398, SEQ ID NO: 422, SEQ ID NO: 426, SEQ ID NO: 400, SEQ ID NO: 428, SEQ ID NO: 424, SEQ ID NO: 591, SEQ ID NO: 592, SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 603, SEQ ID NO: 604, SEQ ID NO: 605, SEQ ID NO: 606, SEQ ID NO: 607, SEQ ID NO: 614, SEQ ID NO: 615, SEQ ID NO: 616, SEQ ID NO: 617, SEQ ID NO: 618, SEQ ID NO: 619, SEQ ID NO: 620, SEQ ID NO: 621, SEQ ID NO: 622, SEQ ID NO: 623, SEQ ID NO: 624, SEQ ID NO: 625, SEQ ID NO: 626, SEQ ID NO: 627, SEQ ID NO: 628, SEQ ID NO: 629, SEQ ID NO: 630, SEQ ID NO: 631, SEQ ID NO: 632, and SEQ ID NO: 633;
- which all characterize binding domains for CDH19 grouped into bin 2;
(c) as depicted in SEQ ID NO: 394, SEQ ID NO: 410, SEQ ID NO: 434, SEQ ID NO: 412, SEQ ID NO: 571, SEQ ID NO: 572, SEQ ID NO: 573, SEQ ID NO: 574, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 578, SEQ ID NO: 579, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 598, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO: 601, SEQ ID NO: 612, and SEQ ID NO: 613;
- which all characterize binding domains for CDH19 grouped into bin 3;
(d) as depicted in SEQ ID NO: 408, SEQ ID NO: 416, SEQ ID NO: 444, SEQ ID NO: 442, SEQ ID NO: 396, SEQ ID NO: 402, SEQ ID NO: 430, SEQ ID NO: 404, SEQ ID NO: 446, SEQ ID NO: 558, SEQ ID NO: 559, SEQ ID NO: 560, SEQ ID NO: 561, SEQ ID NO: 562, SEQ ID NO: 563, SEQ ID NO: 564, SEQ ID NO: 565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO: 568, SEQ ID NO: 569, SEQ ID NO: 570, SEQ ID NO: 583, SEQ ID NO: 584, SEQ ID NO: 585, SEQ ID NO: 586, SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, SEQ ID NO: 611, SEQ ID NO: 635, SEQ ID NO: 636, SEQ ID NO: 637, and SEQ ID NO: 638;
- which all characterize binding domains for CDH19 grouped into bin 4; and
(e) as depicted in SEQ ID NO: 432, SEQ ID NO: 448, SEQ ID NO: 414, SEQ ID NO: 406, and SEQ ID NO: 602;
- which all characterize binding domains for CDH19 grouped into bin 5.

(1) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 362+418, SEQ ID NOs: 364+420, SEQ ID NOs: 485+580, SEQ ID NOs: 486+581, SEQ ID NOs: 487+582, SEQ ID NOs: 492+587, SEQ ID NOs: 493+588, SEQ ID NOs: 494+589, and SEQ ID NOs: 495+590;
- all pairs grouped into bin 1;
(2) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 342+398, SEQ ID NOs: 366+422, SEQ ID NOs: 370+426, SEQ ID NOs: 344+400, SEQ ID NOs: 372+428, SEQ ID NOs: 368+424, SEQ ID NOs: 496+591, SEQ ID NOs: 497+592, SEQ ID NOs: 498+593, SEQ ID NOs: 499+594, SEQ ID NOs: 500+595, SEQ ID NOs: 508+603, SEQ ID NOs: 509+604, SEQ ID NOs: 510+605, SEQ ID NOs: 511+606, SEQ ID NOs: 512+607, SEQ ID NOs: 519+614, SEQ ID NOs: 520+615, SEQ ID NOs: 521+616, SEQ ID NOs: 522+617, SEQ ID NOs: 523+618, SEQ ID NOs: 524+619, SEQ ID NOs: 525+620, SEQ ID NOs: 526+621, SEQ ID NOs: 527+622, SEQ ID NOs: 528+623, SEQ ID NOs: 529+624, SEQ ID NOs: 530+625, SEQ ID NOs: 531+626, SEQ ID NOs: 532+627, SEQ ID NOs: 533+628, SEQ ID NOs: 534+629, SEQ ID NOs: 535+630, SEQ ID NOs: 536+631, SEQ ID NOs: 537+632, and SEQ ID NOs: 538+633;
- all pairs grouped into bin 2;
(3) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 338+394, SEQ ID NOs: 354+410, SEQ ID NOs: 378+434, SEQ ID NOs: 356+412, SEQ ID NOs: 476+571, SEQ ID NOs: 477+572, SEQ ID NOs: 478+573, SEQ ID NOs: 479+574, SEQ ID NOs: 480+575, SEQ ID NOs: 481+576, SEQ ID NOs: 482+577, SEQ ID NOs: 483+578, SEQ ID NOs: 484+579, SEQ ID NOs: 501+596, SEQ ID NOs: 502+597, SEQ ID NOs: 503+598, SEQ ID NOs: 504+599, SEQ ID NOs: 505+600, SEQ ID NOs: 506+601, SEQ ID NOs: 517+612, and SEQ ID NOs: 518+613;
- all pairs grouped into bin 3;
(4) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 352+408, SEQ ID NOs: 360+416, SEQ ID NOs: 388+444, SEQ ID NOs: 386+442, SEQ ID NOs: 340+396, SEQ ID NOs: 346+402, SEQ ID NOs: 374+430, SEQ ID NOs: 348+404, SEQ ID NOs: 390+446, SEQ ID NOs: 463+558, SEQ ID NOs: 464+559, SEQ ID NOs: 465+560, SEQ ID NOs: 466+561, SEQ ID NOs: 467+562, SEQ ID NOs: 468+563, SEQ ID NOs: 469+564, SEQ ID NOs: 470+565, SEQ ID NOs: 471+566, SEQ ID NOs: 472+567, SEQ ID NOs: 473+568, SEQ ID NOs: 474+569, SEQ ID NOs: 475+570, SEQ ID NOs: 488+583, SEQ ID NOs: 489+584, SEQ ID NOs: 490+585, SEQ ID NOs: 491+586, SEQ ID NOs: 513+608, SEQ ID NOs: 514+609, SEQ ID NOs: 515+610, SEQ ID NOs: 516+611, SEQ ID NOs: 540+635, SEQ ID NOs: 541+636, SEQ ID NOs: 542+637, and SEQ ID NOs: 543+638;
- all pairs grouped into bin 4; and
(5) pairs of a VH region and a VL region as depicted in SEQ ID NOs: 376+432, SEQ ID NOs: 392+448, SEQ ID NOs: 358+414, SEQ ID NOs: 350+406, and SEQ ID NOs: 507+602;
- all pairs grouped into bin 5.

(1) a heavy and light chain as depicted in SEQ ID NOs: 644+680, SEQ ID NOs: 650+686, SEQ ID NOs: 747+842, SEQ ID NOs: 748+843, SEQ ID NOs: 749+844, SEQ ID NOs: 754+849, SEQ ID NOs: 755+850, SEQ ID NOs: 756+851, and SEQ ID NOs: 757+852;
- all pairs grouped into bin 1;
(2) a heavy and light chain as depicted in SEQ ID NOs: 660+696, SEQ ID NOs: 662+698, SEQ ID NOs: 668+704, SEQ ID NOs: 674+710, SEQ ID NOs: 672+708, SEQ ID NOs: 658+694, SEQ ID NOs: 758+853, SEQ ID NOs: 759+854, SEQ ID NOs: 760+855, SEQ ID NOs: 761+856, SEQ ID NOs: 762+857, SEQ ID NOs: 770+865, SEQ ID NOs: 771+866, SEQ ID NOs: 772+867, SEQ ID NOs: 773+868, SEQ ID NOs: 774+869, SEQ ID NOs: 781+876, SEQ ID NOs: 782+877, SEQ ID NOs: 783+878, SEQ ID NOs: 784+879, SEQ ID NOs: 785+880, SEQ ID NOs: 786+881, SEQ ID NOs: 787+882, SEQ ID NOs: 788+883, SEQ ID NOs: 789+884, SEQ ID NOs: 790+885, SEQ ID NOs: 791+886, SEQ ID NOs: 792+887, SEQ ID NOs: 793+888, SEQ ID NOs: 794+889, SEQ ID NOs: 795+890, SEQ ID NOs: 796+891, SEQ ID NOs: 797+892, SEQ ID NOs: 798+893, SEQ ID NOs: 799+894, and SEQ ID NOs: 800+895;
- all pairs grouped into bin 2;
(3) a a heavy and light chain as depicted in SEQ ID NOs: 656+692, SEQ ID NOs: 654+690, SEQ ID NOs: 664+700, SEQ ID NOs: 670+706, SEQ ID NOs: 738+833, SEQ ID NOs: 739+834, SEQ ID NOs: 740+835, SEQ ID NOs: 741+836, SEQ ID NOs: 742+837, SEQ ID NOs: 743+838, SEQ ID NOs: 744+839, SEQ ID NOs: 745+840, SEQ ID NOs: 746+841, SEQ ID NOs: 763+858, SEQ ID NOs: 764+859, SEQ ID NOs: 765+860, SEQ ID NOs: 766+861, SEQ ID NOs: 767+862, SEQ ID NOs: 768+863, SEQ ID NOs: 779+874, and SEQ ID NOs: 780+875;
- all pairs grouped into bin 3;
(4) a heavy and light chain as depicted in SEQ ID NOs: 640+676, SEQ ID NOs: 642+678, SEQ ID NOs: 646+682, SEQ ID NOs: 648+684, SEQ ID NOs: 666+702, SEQ ID NOs: 725+820, SEQ ID NOs: 726+821, SEQ ID NOs: 727+822, SEQ ID NOs: 728+823, SEQ ID NOs: 729+824, SEQ ID NOs: 730+825, SEQ ID NOs: 731+826, SEQ ID NOs: 732+827, SEQ ID NOs: 733+828, SEQ ID NOs: 734+829, SEQ ID NOs: 735+830, SEQ ID NOs: 736+831, SEQ ID NOs: 737+832, SEQ ID NOs: 750+845, SEQ ID NOs: 751+846, SEQ ID NOs: 752+847, SEQ ID NOs: 753+848, SEQ ID NOs: 775+870, SEQ ID NOs: 776+871, SEQ ID NOs: 777+872, SEQ ID NOs: 778+873, SEQ ID NOs: 802+897, SEQ ID NOs: 803+898, SEQ ID NOs: 804+899, and SEQ ID NOs: 805+900;
- all pairs grouped into bin 4; and
(5) a heavy and light chain as depicted in SEQ ID NOs: 652+688, and SEQ ID NOs: 769+864 all pairs grouped into bin 5.

In another embodiment the invention is directed to an antibody construct comprising the human antibody or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell as described above that is conjugated to a chemotherapeutic agent.
In one embodiment of the antibody construct of the invention a linker conjugates the chemotherapeutic agent to the human antibody or antigen binding fragment thereof. Accordingly, embodiments of the antibody construct comprising of the invention include antibody drug conjugates (ADCs). Generally the antibody construct comprising of the invention comprises an antibody conjugated to a chemotherapeutic agent, e.g., a cytotoxic agent, a cytostatic agent, a toxin, or a radioactive agent. A linker molecule can be used to conjugate the drug to the antibody. A wide variety of linkers and drugs useful e.g. in ADC technology are known in the art and may be used in embodiments of the present invention. (See US20090028856; US2009/0274713; US2007/0031402; WO2005/084390; WO2009/099728; U.S. Pat. Nos. 5,208,020; 5,416,064; 5,475,092; 5,585,499; 6,436,931; 6,372,738; and 6,340,701, all incorporated herein by reference).
In certain embodiments, the antibody construct comprising of the invention comprises a linker made up of one or more linker components. Exemplary linker components include 6-maleimidocaproyl, maleimidopropanoyl, valine-citrulline, alanine-phenylalanine, p-aminobenzyloxycarbonyl, and those resulting from conjugation with linker reagents, including, but not limited to, N-succinimidyl 4-(2-pyridylthio) pentanoate (“SPP”), N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (“SMCC,” also referred to herein also as “MCC”), and N-succinimidyl (4-iodo-acetyl) aminobenzoate (“SIAB”). Linkers may be a “cleavable” linker or a “non-cleavable” linker (Ducry and Stump, Bioconjugate Chem. 2010, 21, 5-13; incorporated herein by reference in its entirety) Cleavable linkers are designed to release the drug when subjected to certain environment factors, e.g., when internalized into the target cell. Cleavable linkers include acid labile linkers, protease sensitive linkers, photolabile linkers, dimethyl linker or disulfide-containing linkers. Non-cleavable linkers tend to remain covalently associated with at least one amino acid of the antibody and the drug upon internalization by and degradation within the target cell. An exemplary non-cleavable linker is MCC.
In a preferred embodiment of the antibody construct of the invention the linker is a non-cleavable linker.
It is also preferred that the linker in the antibody construct of the invention comprises MCC.
In a further embodiment of the antibody construct of the invention the chemotherapeutic agent is conjugated to one or more lysines contained in the human antibody or antigen binding fragment thereof.
In certain embodiments, the antibody of the invention is conjugated to a chemotherapeutic agent. Examples of chemotherapeutic agents include alkylating agents, such as thiotepa and cyclophosphamide (CYTOXAN™); alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines, such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CBI-TMI); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlomaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics, such as the enediyne antibiotics (e.g. calicheamicin, especially calicheamicin .gammal and calicheamicin theta I, see, e.g., Angew Chem. Intl. Ed. Engl. 33:183-186 (1994); dynemicin, including dynemicin A; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromomophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin; chromomycins, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, nitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites, such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues, such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs, such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, 5-FU; androgens, such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals, such as aminoglutethimide, mitotane, trilostane; folic acid replenisher, such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidamine; maytansinoids, such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidamol; nitracrine; pentostatin; phenamet; pirarubicin; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK®; razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2′,2″-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g. paclitaxel (TAXOL™, Bristol-Myers Squibb Oncology, Princeton, N.J.) and doxetaxel (TAXOTERE®, Rhone-Poulenc Rorer, Antony, France); chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbine; novantrone; teniposide; 65 daunomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylomithine (DMFO); retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above. Also included in this definition are anti-hormonal agents that act to regulate or inhibit hormone action on tumors, such as anti-estrogens including for example tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and toremifene (Fareston); and anti-androgens, such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; siRNA and pharmaceutically acceptable salts, acids or derivatives of any of the above. Other chemotherapeutic agents that can be used with the present invention are disclosed in US Publication No. 20080171040 or US Publication No. 20080305044 and are incorporated in their entirety by reference.
It is contemplated that an antibody may be conjugated to two or more different chemotherapeutic agents or a pharmaceutical composition may comprise a mixture of antibodies wherein the antibody component is identical except for being conjugated to a different chemotherapeutic agent. Such embodiments may be useful for targeting multiple biological pathways with a target cell.
In preferred embodiments, the antibody construct comprising of the invention comprises an antibody conjugated to one or more maytansinoid molecules, which are mitotic inhibitors that act by inhibiting tubulin polymerization. Maytansinoids, including various modifications, are described in U.S. Pat. Nos. 3,896,111; 4,151,042; 4,137,230; 4,248,870; 4,256,746; 4,260,608; 4,265,814; 4,294,757; 4,307,016; 4,308,268; 4,309,428; 4,313,946; 4,315,929; 4,317,821; 4,322,348; 4331598; 4361650; 4364866; 4424219; 4450254; 4362663; 4371533; and WO 2009/099728. Maytansinoid drug moieties may be isolated from natural sources, produced using recombinant technology, or prepared synthetically. Exemplary maytansinoids include C-19-dechloro (U.S. Pat. No. 4,256,746), C-20-hydroxy (or C-20-demethyl) +/−C-19-dechloro (U.S. Pat. Nos. 4,307,016 and 4,361,650), C-20-demethoxy (or C-20-acyloxy (—OCOR), +/−dechrolo (U.S. Pat. No. 4,294,757), C-9-SH (U.S. Pat. No. 4,424,219), C-14-alkoxymethyl (demethoxy/CH2OR) (U.S. Pat. No. 4,331,598), C-14-hydroxymethyl or acyloxymethyl (CH2OH or CH2OAc) (U.S. Pat. No. 4,450,254), C-15-hydroxy/acyloxy (U.S. Pat. No. 4,364,866), C-15-methoxy (U.S. Pat. Nos. 4,313,946 and 4,315,929), C-18-N-demethyl (U.S. Pat. Nos. 4,362,663 and 4,322,348), and 4,5-deoxy (U.S. Pat. No. 4,371,533).
Various positions on maytansinoid compounds may be used as the linkage position, depending upon the type of link desired. For example, for forming an ester linkage, the C-3 position having a hydroxyl group, the C-14 position modified with hydrozymethyl, the C-15 position modified with a hydroxyl a group, and the C-20 position having a hydroxyl group are all suitable (U.S. Pat. Nos. 5,208,020, RE39,151, and 6,913,748; US Patent Appl. Pub. Nos. 20060167245 and 20070037972, and WO 2009099728).
Preferred maytansinoids include those known in the art as DM1, DM3, and DM4 (US Pat. Appl. Pub. Nos. 2009030924 and 20050276812, incorporated herein by reference). In one embodiment of the antibody construct of the invention the chemotherapeutic agent is DM1. Accordingly, in a preferred embodiment the antibody construct of the invention is an the human antibody or antigen binding fragment thereof conjugated to one or more DM1 molecules.
ADCs containing maytansinoids, methods of making such ADCs, and their therapeutic use are disclosed in U.S. Pat. Nos. 5,208,020 and 5,416,064, US Pat. Appl. Pub. No. 20050276812, and WO 2009099728 (all incorporated by reference herein). Linkers that are useful for making maytansinoid ADCs are know in the art (U.S. Pat. No. 5,208,020 and US Pat. Appl. Pub. Nos. 2005016993 and 20090274713; all incorporated herein by reference). Maytansinoid ADCs comprising an SMCC linker may be prepared as disclosed in US Pat. Publ. No. 2005/0276812.
In certain embodiments, the antibody construct comprising of the invention comprises an antibody conjugated to DM1 with an SMCC linker.
An antibody construct comprising of the invention may have 1 to 20 chemotherapeutic agents per antibody. Compositions of ADCs may be characterized by the average number of drug moieties per antibody molecule in the composition. The average number of drug moieties may be determined by conventional means such as mass spectrometry, immunoassay, and HPLC. In some instances, a homogeneous ADC population may be separated and purified by means of reverse phase HPLC or electrophoresis. Thus, pharmaceutical ADC compositions may contain a heterogeneous or homogeneous population of antibodies linked to 1, 2, 3, 4, 5, 6, 7 or more drug moieties.
Thus, in a preferred embodiment of the antibody construct of the invention the average number of DM1 molecules per antibody construct is between 1 and 10.
It is also preferred for the antibody construct of the invention that the average number of DM1 molecules per antibody construct is between 3 and 7.
Moreover, it is preferred for the antibody construct of the invention that the average number of DM1 molecules per antibody construct is between 4 and 6.
Embodiments of the invention include antibody constructs comprising an average of about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20 DM1 molecules per antibody.
In a further alternative embodiment of the antibody construct of the invention the average number of DM1 molecules per antibody construct is about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0.
In one embodiment the antibody respectively the antibody construct of the invention comprises an effector function-enhanced antibody. One of the functions of the Fc portion of an antibody is to communicate to the immune system when the antibody binds its target. This is considered “effector function”. Communication leads to antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and/or complement dependent cytotoxicity (CDC). ADCC and ADCP are mediated through the binding of the Fc to Fc receptors on the surface of cells of the immune system. CDC is mediated through the binding of the Fc with proteins of the complement system, e.g., C1q.
The IgG subclasses vary in their ability to mediate effector functions. For example IgG1 is much superior to IgG2 and IgG4 at mediating ADCC and CDC. Thus, in embodiments wherein a cell expressing CDH19 is targeted for destruction, an anti-CDH19 IgG1 antibody would be preferred.
The effector function of an antibody can be increased, or decreased, by introducing one or more mutations into the Fc. Embodiments of the invention include antigen binding proteins, e.g., antibodies, having an Fc engineered to increase effector function (U.S. Pat. No. 7,317,091 and Strohl, Curr. Opin. Biotech., 20:685-691, 2009; both incorporated herein by reference in its entirety). Exemplary IgG1 Fc molecules having increased effector function include (based on the Kabat numbering scheme) those have the following substitutions:
S239D/I332E
S239D/A330S/I332E
S239D/A330L/I332E
S298A/D333A/K334A
P247I/A339D
P247I/A339Q
D280H/K290S
D280H/K290S/S298D
D280H/K290S/S298V
F243L/R292P/Y300L
F243L/R292P/Y300L/P396L
F243L/R292P/Y300L/V3051/P396L
G236A/S239D/I332E
K326A/E333A
K326W/E333S
K290E/S298G/T299A
K290N/S298G/T299A
K290E/5298G/T299A/K326E
K290N/S298G/T299A/K326E
Further embodiments of the invention include antibodies, having an Fc engineered to decrease effector function. Exemplary Fc molecules having decreased effector function include (based on the Kabat numbering scheme) those have the following substitutions:
N297A (IgG1)
L234A/L235A (IgG1)
V234A/G237A (IgG2)
L235A/G237A/E318A (IgG4)
H2680/V309L/A330S/A331S (IgG2)
C220S/C226S/C229S/P238S (IgG1)
C226S/C229S/E233P/L234V/L235A (IgG1)
L234F/L235E/P331S (IgG1)
S267E/L328F (IgG1)
Another method of increasing effector function of IgG Fc-containing proteins is by reducing the fucosylation of the Fc. Removal of the core fucose from the biantennary complex-type oligosachharides attached to the Fc greatly increased ADCC effector function without altering antigen binding or CDC effector function. Several ways are known for reducing or abolishing fucosylation of Fc-containing molecules, e.g., antibodies. These include recombinant expression in certain mammalian cell lines including a FUT8 knockout cell line, variant CHO line Lec13, rat hybridoma cell line YB2/0, a cell line comprising a small interfering RNA specifically against the FUT8 gene, and a cell line coexpressing B-1,4-N-acetylglucosaminyltransferase III and Golgi α-mannosidase II. Alternatively, the Fc-containing molecule may be expressed in a non-mammalian cell such as a plant cell, yeast, or prokaryotic cell, e.g., E. coli. Thus, in certain embodiments of the invention, a composition comprises an antibody, e.g., Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, or Ab8, having reduced fucosylation or lacking fucosylation altogether.
The invention further provides an isolated nucleic acid molecule or sequence encoding a human antibody or antigen binding fragment thereof of the invention.
Furthermore, the invention provides a vector comprising a nucleic acid sequence of the invention. Moreover, the invention provides a host cell transformed or transfected with the nucleic acid sequence of the invention or with a vector comprising the nucleic acid molecule.
In a further embodiment the invention provides a process for the production of a human antibody or an antigen binding fragment thereof of the invention, said process comprising culturing a host cell of the invention under conditions allowing the expression of the human antibody or antigen binding fragment thereof of the invention and recovering the produced antibody or antigen binding fragment thereof from the culture.
In a further embodiment the invention provides a process for the production of an antibody construct comprising a human antibody or an antigen binding fragment thereof of the invention, said process comprising culturing a host cell of the invention under conditions allowing the expression of the human antibody or antigen binding fragment thereof of the invention and recovering the produced antibody or antigen binding fragment thereof from the culture, and conjugating a chemotherapeutic agent to the recovered antibody or antigen binding fragment thereof to produce the antibody conjugate.
Moreover, the invention provides a pharmaceutical composition comprising a human antibody or antigen binding fragment thereof of the invention or an antibody construct of the invention or produced according to the process of the invention in admixture with a pharmaceutically acceptable carrier thereof.
The formulations described herein are useful as pharmaceutical compositions in the treatment, amelioration and/or prevention of the pathological medical condition as described herein in a patient in need thereof. The term “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Treatment includes the application or administration of the formulation to the body, an isolated tissue, or cell from a patient who has a disease/disorder, a symptom of a disease/disorder, or a predisposition toward a disease/disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease, the symptom of the disease, or the predisposition toward the disease.
Those “in need of treatment” include those already with the disorder, as well as those in which the disorder is to be prevented. The term “disease” is any condition that would benefit from treatment with the protein formulation described herein. This includes chronic and acute disorders or diseases including those pathological conditions that predispose the mammal to the disease in question. Non-limiting examples of diseases/disorders to be treated herein include proliferative disease, a tumorous disease, or an immunological disorder.
In some embodiments, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of one or a plurality of the a human antibody or antigen binding fragment thereof of the invention or an antibody construct of the invention together with a pharmaceutically effective diluents, carrier, solubilizer, emulsifier, preservative, and/or adjuvant. In certain embodiments, the antigen binding protein is an antibody, including a drug-conjugated antibody or a bispecific antibody. Pharmaceutical compositions of the invention include, but are not limited to, liquid, frozen, and lyophilized compositions.
Preferably, formulation materials are nontoxic to recipients at the dosages and concentrations employed. In specific embodiments, pharmaceutical compositions comprising a therapeutically effective amount of a human antibody or antigen binding fragment thereof of the invention or an antibody construct of the invention.
In certain embodiments, the pharmaceutical composition may contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine, proline, or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol sorbitol); delivery vehicles; diluents; excipients and/or pharmaceutical adjuvants. See, REMINGTON'S PHARMACEUTICAL SCIENCES, 18″ Edition, (A. R. Genrmo, ed.), 1990, Mack Publishing Company.
In certain embodiments, the optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format and desired dosage. See, for example, REMINGTON'S PHARMACEUTICAL SCIENCES, supra. In certain embodiments, such compositions may influence the physical state, stability, rate of in vivo release and rate of in vivo clearance of the antigen binding proteins of the invention. In certain embodiments, the primary vehicle or carrier in a pharmaceutical composition may be either aqueous or non-aqueous in nature. For example, a suitable vehicle or carrier may be water for injection, physiological saline solution or artificial cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. In specific embodiments, pharmaceutical compositions comprise Tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, and may further include sorbitol or a suitable substitute therefore. In certain embodiments of the invention, human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention compositions may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents (REMINGTON'S PHARMACEUTICAL SCIENCES, supra) in the form of a lyophilized cake or an aqueous solution. Further, in certain embodiments, the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention may be formulated as a lyophilizate using appropriate excipients such as sucrose.
The pharmaceutical compositions of the invention can be selected for parenteral delivery. Alternatively, the compositions may be selected for inhalation or for delivery through the digestive tract, such as orally. Preparation of such pharmaceutically acceptable compositions is within the skill of the art. The formulation components are present preferably in concentrations that are acceptable to the site of administration. In certain embodiments, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8.
When parenteral administration is contemplated, the therapeutic compositions for use in this invention may be provided in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising the desired human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is sterile distilled water in which the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention is formulated as a sterile, isotonic solution, properly preserved. In certain embodiments, the preparation can involve the formulation of the desired molecule with an agent, such as injectable microspheres, bio-erodible particles, polymeric compounds (such as polylactic acid or polyglycolic acid), beads or liposomes, that may provide controlled or sustained release of the product which can be delivered via depot injection. In certain embodiments, hyaluronic acid may also be used, having the effect of promoting sustained duration in the circulation. In certain embodiments, implantable drug delivery devices may be used to introduce the desired antigen binding protein.
Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations involving human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention in sustained- or controlled-delivery formulations. Techniques for formulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. See, for example, International Patent Application No. PCT/US93/00829, which is incorporated by reference and describes controlled release of porous polymeric microparticles for delivery of pharmaceutical compositions. Sustained-release preparations may include semipermeable polymer matrices in the form of shaped articles, e.g., films, or microcapsules. Sustained release matrices may include polyesters, hydrogels, polylactides (as disclosed in U.S. Pat. No. 3,773,919 and European Patent Application Publication No. EP 058481, each of which is incorporated by reference), copolymers of L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al., 1983, Biopolymers 2:547-556), poly (2-hydroxyethyl-methacrylate) (Langer et al., 1981, J. Biomed. Mater. Res. 15:167-277 and Langer, 1982, Chem. Tech. 12:98-105), ethylene vinyl acetate (Langer et al., 1981, supra) or poly-D(−)-3-hydroxybutyric acid (European Patent Application Publication No. EP 133,988). Sustained release compositions may also include liposomes that can be prepared by any of several methods known in the art. See, e.g., Eppstein et al., 1985, Proc. Natl. Acad. Sci. U.S.A. 82:3688-3692; European Patent Application Publication Nos. EP 036,676; EP 088,046 and EP 143,949, incorporated by reference.
Pharmaceutical compositions used for in vivo administration are typically provided as sterile preparations. Sterilization can be accomplished by filtration through sterile filtration membranes. When the composition is lyophilized, sterilization using this method may be conducted either prior to or following lyophilization and reconstitution. Compositions for parenteral administration can be stored in lyophilized form or in a solution. Parenteral compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.
Aspects of the invention includes self-buffering human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention formulations, which can be used as pharmaceutical compositions, as described in international patent application WO 06138181A2 (PCT/US2006/022599), which is incorporated by reference in its entirety herein.
As discussed above, certain embodiments provide human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention protein compositions, particularly pharmaceutical compositions of the invention, that comprise, in addition to the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention, one or more excipients such as those illustratively described in this section and elsewhere herein. Excipients can be used in the invention in this regard for a wide variety of purposes, such as adjusting physical, chemical, or biological properties of formulations, such as adjustment of viscosity, and or processes of the invention to improve effectiveness and or to stabilize such formulations and processes against degradation and spoilage due to, for instance, stresses that occur during manufacturing, shipping, storage, pre-use preparation, administration, and thereafter.
A variety of expositions are available on protein stabilization and formulation materials and methods useful in this regard, such as Arakawa et al., “Solvent interactions in pharmaceutical formulations,” Pharm Res. 8(3): 285-91 (1991); Kendrick et al., “Physical stabilization of proteins in aqueous solution,” in: RATIONAL DESIGN OF STABLE PROTEIN FORMULATIONS: THEORY AND PRACTICE, Carpenter and Manning, eds. Pharmaceutical Biotechnology. 13: 61-84 (2002), and Randolph et al., “Surfactant-protein interactions,” Pharm Biotechnol. 13: 159-75 (2002), each of which is herein incorporated by reference in its entirety, particularly in parts pertinent to excipients and processes of the same for self-buffering protein formulations in accordance with the current invention, especially as to protein pharmaceutical products and processes for veterinary and/or human medical uses.
Salts may be used in accordance with certain embodiments of the invention to, for example, adjust the ionic strength and/or the isotonicity of a formulation and/or to improve the solubility and/or physical stability of a protein or other ingredient of a composition in accordance with the invention.
As is well known, ions can stabilize the native state of proteins by binding to charged residues on the protein's surface and by shielding charged and polar groups in the protein and reducing the strength of their electrostatic interactions, attractive, and repulsive interactions. Ions also can stabilize the denatured state of a protein by binding to, in particular, the denatured peptide linkages (—CONH) of the protein. Furthermore, ionic interaction with charged and polar groups in a protein also can reduce intermolecular electrostatic interactions and, thereby, prevent or reduce protein aggregation and insolubility.
Ionic species differ significantly in their effects on proteins. A number of categorical rankings of ions and their effects on proteins have been developed that can be used in formulating pharmaceutical compositions in accordance with the invention. One example is the Hofmeister series, which ranks ionic and polar non-ionic solutes by their effect on the conformational stability of proteins in solution. Stabilizing solutes are referred to as “kosmotropic.” Destabilizing solutes are referred to as “chaotropic.” Kosmotropes commonly are used at high concentrations (e.g., >1 molar ammonium sulfate) to precipitate proteins from solution (“salting-out”). Chaotropes commonly are used to denture and/or to solubilize proteins (“salting-in”). The relative effectiveness of ions to “salt-in” and “salt-out” defines their position in the Hofmeister series.
Free amino acids can be used in human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention formulations in accordance with various embodiments of the invention as bulking agents, stabilizers, and antioxidants, as well as other standard uses. Lysine, proline, serine, and alanine can be used for stabilizing proteins in a formulation. Glycine is useful in lyophilization to ensure correct cake structure and properties. Arginine may be useful to inhibit protein aggregation, in both liquid and lyophilized formulations. Methionine is useful as an antioxidant.
Polyols include sugars, e.g., mannitol, sucrose, and sorbitol and polyhydric alcohols such as, for instance, glycerol and propylene glycol, and, for purposes of discussion herein, polyethylene glycol (PEG) and related substances. Polyols are kosmotropic. They are useful stabilizing agents in both liquid and lyophilized formulations to protect proteins from physical and chemical degradation processes. Polyols also are useful for adjusting the tonicity of formulations.
Among polyols useful in select embodiments of the invention is mannitol, commonly used to ensure structural stability of the cake in lyophilized formulations. It ensures structural stability to the cake. It is generally used with a lyoprotectant, e.g., sucrose. Sorbitol and sucrose are among preferred agents for adjusting tonicity and as stabilizers to protect against freeze-thaw stresses during transport or the preparation of bulks during the manufacturing process. Reducing sugars (which contain free aldehyde or ketone groups), such as glucose and lactose, can glycate surface lysine and arginine residues. Therefore, they generally are not among preferred polyols for use in accordance with the invention. In addition, sugars that form such reactive species, such as sucrose, which is hydrolyzed to fructose and glucose under acidic conditions, and consequently engenders glycation, also is not among preferred polyols of the invention in this regard. PEG is useful to stabilize proteins and as a cryoprotectant and can be used in the invention in this regard.
Embodiments of the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention formulations further comprise surfactants. Protein molecules may be susceptible to adsorption on surfaces and to denaturation and consequent aggregation at air-liquid, solid-liquid, and liquid-liquid interfaces. These effects generally scale inversely with protein concentration. These deleterious interactions generally scale inversely with protein concentration and typically are exacerbated by physical agitation, such as that generated during the shipping and handling of a product.
Surfactants routinely are used to prevent, minimize, or reduce surface adsorption. Useful surfactants in the invention in this regard include polysorbate 20, polysorbate 80, other fatty acid esters of sorbitan polyethoxylates, and poloxamer 188.
Surfactants also are commonly used to control protein conformational stability. The use of surfactants in this regard is protein-specific since, any given surfactant typically will stabilize some proteins and destabilize others.
Polysorbates are susceptible to oxidative degradation and often, as supplied, contain sufficient quantities of peroxides to cause oxidation of protein residue side-chains, especially methionine. Consequently, polysorbates should be used carefully, and when used, should be employed at their lowest effective concentration. In this regard, polysorbates exemplify the general rule that excipients should be used in their lowest effective concentrations.
Embodiments of human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention formulations further comprise one or more antioxidants. To some extent deleterious oxidation of proteins can be prevented in pharmaceutical formulations by maintaining proper levels of ambient oxygen and temperature and by avoiding exposure to light. Antioxidant excipients can be used as well to prevent oxidative degradation of proteins. Among useful antioxidants in this regard are reducing agents, oxygen/free-radical scavengers, and chelating agents. Antioxidants for use in therapeutic protein formulations in accordance with the invention preferably are water-soluble and maintain their activity throughout the shelf life of a product. EDTA is a preferred antioxidant in accordance with the invention in this regard.
Antioxidants can damage proteins. For instance, reducing agents, such as glutathione in particular, can disrupt intramolecular disulfide linkages. Thus, antioxidants for use in the invention are selected to, among other things, eliminate or sufficiently reduce the possibility of themselves damaging proteins in the formulation.
Formulations in accordance with the invention may include metal ions that are protein co-factors and that are necessary to form protein coordination complexes, such as zinc necessary to form certain insulin suspensions. Metal ions also can inhibit some processes that degrade proteins. However, metal ions also catalyze physical and chemical processes that degrade proteins.
Magnesium ions (10-120 mM) can be used to inhibit isomerization of aspartic acid to isoaspartic acid. Ca+2 ions (up to 100 mM) can increase the stability of human deoxyribonuclease. Mg+2, Mn+2, and Zn+2, however, can destabilize rhDNase. Similarly, Ca+2 and Sr+2 can stabilize Factor VIII, it can be destabilized by Mg+2, Mn+2 and Zn+2, Cu+2 and Fe+2, and its aggregation can be increased by Al+3 ions.
Embodiments of the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention formulations further comprise one or more preservatives. Preservatives are necessary when developing multi-dose parenteral formulations that involve more than one extraction from the same container. Their primary function is to inhibit microbial growth and ensure product sterility throughout the shelf-life or term of use of the drug product. Commonly used preservatives include benzyl alcohol, phenol and m-cresol. Although preservatives have a long history of use with small-molecule parenterals, the development of protein formulations that includes preservatives can be challenging. Preservatives almost always have a destabilizing effect (aggregation) on proteins, and this has become a major factor in limiting their use in multi-dose protein formulations. To date, most protein drugs have been formulated for single-use only. However, when multi-dose formulations are possible, they have the added advantage of enabling patient convenience, and increased marketability. A good example is that of human growth hormone (hGH) where the development of preserved formulations has led to commercialization of more convenient, multi-use injection pen presentations. At least four such pen devices containing preserved formulations of hGH are currently available on the market. Norditropin (liquid, Novo Nordisk), Nutropin AQ (liquid, Genentech) & Genotropin (lyophilized—dual chamber cartridge, Pharmacia & Upjohn) contain phenol while Somatrope (Eli Lilly) is formulated with m-cresol. Several aspects need to be considered during the formulation and development of preserved dosage forms. The effective preservative concentration in the drug product must be optimized. This requires testing a given preservative in the dosage form with concentration ranges that confer anti-microbial effectiveness without compromising protein stability.
As might be expected, development of liquid formulations containing preservatives are more challenging than lyophilized formulations. Freeze-dried products can be lyophilized without the preservative and reconstituted with a preservative containing diluent at the time of use. This shortens the time for which a preservative is in contact with the protein, significantly minimizing the associated stability risks. With liquid formulations, preservative effectiveness and stability should be maintained over the entire product shelf-life (about 18 to 24 months). An important point to note is that preservative effectiveness should be demonstrated in the final formulation containing the active drug and all excipient components.
Human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention generally will be designed for specific routes and methods of administration, for specific administration dosages and frequencies of administration, for specific treatments of specific diseases, with ranges of bio-availability and persistence, among other things. Formulations thus may be designed in accordance with the invention for delivery by any suitable route, including but not limited to orally, aurally, opthalmically, rectally, and vaginally, and by parenteral routes, including intravenous and intraarterial injection, intramuscular injection, and subcutaneous injection.
Once the pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution, suspension, gel, emulsion, solid, crystal, or as a dehydrated or lyophilized powder. Such formulations may be stored either in a ready-to-use form or in a form (e.g., lyophilized) that is reconstituted prior to administration. The invention also provides kits for producing a single-dose administration unit. The kits of the invention may each contain both a first container having a dried protein and a second container having an aqueous formulation. In certain embodiments of this invention, kits containing single and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes) are provided. The therapeutically effective amount of a human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention protein-containing pharmaceutical composition to be employed will depend, for example, upon the therapeutic context and objectives. One skilled in the art will appreciate that the appropriate dosage levels for treatment will vary depending, in part, upon the molecule delivered, the indication for which the human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention is being used, the route of administration, and the size (body weight, body surface or organ size) and/or condition (the age and general health) of the patient. In certain embodiments, the clinician may titer the dosage and modify the route of administration to obtain the optimal therapeutic effect. A typical dosage may range from about 0.1 μg/kg to up to about 30 mg/kg or more, depending on the factors mentioned above. In specific embodiments, the dosage may range from 1.0 μg/kg up to about 20 mg/kg, optionally from 10 μg/kg up to about 10 mg/kg or from 100 μg/kg up to about 5 mg/kg.
A therapeutic effective amount of a human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention preferably results in a decrease in severity of disease symptoms, in increase in frequency or duration of disease symptom-free periods or a prevention of impairment or disability due to the disease affliction. For treating CDH19-expressing tumors, a therapeutically effective amount of human antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention, e.g. an anti-CDH19 antibody construct (ADC construct), preferably inhibits cell growth or tumor growth by at least about 20%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% relative to untreated patients. The ability of a compound to inhibit tumor growth may be evaluated in an animal model predictive of efficacy in human tumors.
Pharmaceutical compositions may be administered using a medical device. Examples of medical devices for administering pharmaceutical compositions are described in U.S. Pat. Nos. 4,475,196; 4,439,196; 4,447,224; 4,447, 233; 4,486,194; 4,487,603; 4,596,556; 4,790,824; 4,941,880; 5,064,413; 5,312,335; 5,312,335; 5,383,851; and 5,399,163, all incorporated by reference herein.
In one embodiment the invention provides the human antibody or antigen binding fragment thereof of the invention, the antibody construct of the invention, or produced according to the process of the invention for use in the prevention, treatment or amelioration of a melanoma disease or metastatic melanoma disease. Preferably, the melanoma disease or metastatic melanoma disease is selected from the group consisting of superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, acral lentiginous melanoma and nodular melanoma.
The invention also provides a method for the treatment or amelioration of a melanoma disease or metastatic melanoma disease, comprising the step of administering to a subject in need thereof the antibody or antigen binding fragment thereof of the invention, the antibody construct of the invention, an antibody or antigen binding fragment thereof of the invention or the antibody construct of the invention produced according to the process of the invention or a pharmaceutical composition of the invention.
In a preferred embodiment method the invention the melanoma disease or metastatic melanoma disease is selected from the group consisting of superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, acral lentiginous melanoma and nodular melanoma.
In a further embodiment, the invention provides a kit comprising an antibody or antigen binding fragment thereof of the invention, an antibody construct of the invention, an antibody or antigen binding fragment thereof of the invention or the antibody construct produced according to the process of the invention, a vector of the invention, and/or a host cell of the invention.
It should be understood that the inventions herein are not limited to particular methodology, protocols, or reagents, as such can vary. The discussion and examples provided herein are presented for the purpose of describing particular embodiments only and are not intended to limit the scope of the present invention, which is defined solely by the claims.
All publications and patents cited throughout the text of this specification (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. To the extent the material incorporated by reference contradicts or is inconsistent with this specification, the specification will supersede any such material.

EXAMPLES

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

Example 1—Fully Human Monoclonal Antibodies Against CDH19

1.1 Immunization:
Fully human antibodies to Cadherin-19 (CDH19) were generated using XENOMOUSE® technology, transgenic mice engineered to express diverse repertoires of fully human IgGκ and IgGλ antibodies of the corresponding isotype. (U.S. Pat. Nos. 6,114,598; 6,162,963; 6,833,268; 7,049,426; 7,064,244, which are incorporated herein by reference in their entirety; Green et al., 1994, Nature Genetics 7:13-21; Mendez et al., 1997, Nature Genetics 15:146-156; Green and Jakobovitis, 1998, J. Ex. Med. 188:483-495; Kellermann and Green, Current Opinion in Biotechnology 13, 593-597, 2002).
Mice were immunized with multiple forms of Cadherin-19 immunogen, including: (1) full length human and cynomologous (“cyno”) monkey cadherin-19, (2) secreted Cadherin-19 ecto-domain (amino acids 1-596), and (3) a truncated membrane bound form of human cadherin-19 (amino acids 1-624). Mice were immunized over a period of 8 to 10 weeks with a range of 16-18 boosts.
Sera were collected at approximately 5 and 9 weeks after the first injection and specific titers were determined by FACs staining of recombinant Cadherin-19 receptor transiently expressed on CHO—S cells. A total of 37 animals were identified with specific immune responses, these animals were pooled into 3 groups and advanced to antibody generation.
1.2 Preparation of Monoclonal Antibodies
Animals exhibiting suitable titers were identified, and lymphocytes were obtained from draining lymph nodes and, if necessary, pooled for each cohort. Lymphocytes were dissociated from lymphoid tissue by grinding in a suitable medium (for example, Dulbecco's Modified Eagle Medium (DMEM); obtainable from Invitrogen, Carlsbad, Calif.) to release the cells from the tissues, and suspended in DMEM. B cells were selected and/or expanded using standard methods, and fused with suitable fusion partner using techniques that were known in the art.
After several days of culture, the hybridoma supernatants were collected and subjected to screening assays as detailed in the examples below, including confirmation of binding to human and cynomologous monkey as well as the ability to kill cell lines in secondary antibody-drug conjugate Bioassays. Hybridoma lines that were identified to have the binding and functional properties of interest were then further selected and subjected to standard cloning and subcloning techniques. Clonal lines were expanded in vitro, and the secreted human antibodies obtained for analysis and V gene sequencing was performed.
1.3 Selection of Cadherin-19 Receptor Specific Binding Antibodies by FMAT
After 14 days of culture, hybridoma supernatants were screened for CDH19-specific monoclonal antibodies by Fluorometric Microvolume Assay Technology (FMAT) (Applied Biosystems, Foster City, Calif.). The supernatants were screened against adherent CHO cells transiently transfected with human Cadherin-19 and counter screened against CHO cells transiently transfected with the same expression plasmid that did not contain the Cadherin-19 gene.
After multiple screening campaigns, a panel of 1570 anti-Cadherin-19 binding hybridoma lines were identified and advanced to further characterization assays.

Example 2—Assessment of Fully Human Monoclonal Antibodies Against CDH19

2.1 Additional Binding Characterization by Flow Cytometry (FACs)
FACS binding assays were performed to evaluate the binding of the anti-Cadherin-19 receptor specific antibodies to endogenous Cadherin-19 receptor expressed on the CHL-1 tumor cell lines. In addition, cross-reactive binding to murine and cynomologous monkey Cadherin-19 orthologues was also evaluated by FACs using recombinant forms of the various receptors transiently expressed on 293T cells.
FACs assays were performed by incubating hybridoma supernatants with 10,000 to 25,000 cells in PBS/2% Fetal bovine serum/2 mM Calcium Chloride at 4° C. for one hour followed by two washes with PBS/2% Fetal bovine serum/2 mM Calcium Chloride. Cells were then treated with florochrome-labeled secondary antibodies at 4° C. followed by one wash. The cells were resuspended in 50 μl of PBS/2% FBS and antibody binding was analyzed using a FACSCalibur™ instrument.
2.2 Antibody Drug Conjugate Screening of Fully Human Antibodies Derived from XenoMouse® Hybridomas
Cell killing through antibody drug conjugates requires the delivery of the conjugate into a cell through internalization and the catabolism of the drug-conjugate into a form that it is toxic to the cell. To identify antibodies with these properties, CDH19-positive cell lines (Colo-699 or CHL-1) were seeded at low cell densities and allowed to adhere overnight in a 384 well plate. XENOMOUSE® hybridoma samples containing fully human anti-CDH19 antibodies were then added to these cells in the presence of a high concentration of a goat anti-human Fc monovalent Fab conjugated with DM1 (DM1-Fab) at a relatively low drug-antibody ratio (DAR) (˜1.3). The cells were incubated for 96 hours at 37° C. and 5% CO₂in the presence of the antibody samples and the DM1-Fab. At the end of this time, the cell viability was assessed using the CellTiter-Glo® Luminescent Cell Viability reagent (Promega) according to manufacturer's recommendations.
An example of the cell viability data with the Colo-699 cells is shown in FIG. 1 and FIG. 2. The antibodies capable of delivering the DM1-Fab to the cells and inhibiting the cell growth read out with a lower luminescent signal (RLU). The top antibodies of interest from this screen are observed in the lower left corner of FIG. 1 and are denoted as open circles.
These antibodies were taken forward into a cell viability assay on CHL-1 cells. The average cell viability data from the CHL-1 assay is plotted against the average cell viability data from the Colo-699 assay (FIG. 2). The antibodies that had activity on both the Colo-699 and the CHL-1 cells are denoted as open circles on the left-hand side of the FIG. 2.
This assay was run concurrently with the FACs antibody binding assay above (2.2), and the results from these two studies were used to select the antibodies for further characterization. In total, 1570 antibodies were run through these cell based viability assays and approximately 44 antibodies were selected on the bases of in vitro cell killing and/or antibody binding for sub-cloning, V gene sequencing and expressed in recombinant form for further characterization assays as described below.
These 44 antibodies were again assayed as in Example 2 and 19 antibodies were selected that contained unique sequences. Of these 19 antibodies, 18 antibodies were analyzed and their properties characterized in Table 2 below. The data in this table was generated using FACs binding on recombinant human and cynomologous CDH-19, +/−Calcium (Ca⁺²) binding data on 293/CDH-19 transfectants, binding to endogenous CDH-19 on CHL-1 and Colo699 tumor cells and competition with the antibody designated as 4A9 in the table. These experiments provided the further characterizations for the grouping of these antibodies into 5 groups or bins.

TABLE 2

Binning of Lead panel using Antibody Binding Information

	LMR
Bin	Sequence/	Clone
ID	Ab ID	ID	Bin Characteristics

1	13589	4A9	High Endogenous binding, Calcium
	13591	4F7	insensitive, sequence clustered, moderate
			cyno complete 4A9 competitor
2	13885	19B5	High Endogenous binding, Calcium
	13880	25F8	insensitive, sequence
	13882	26D1	clustered, Good cyno,
	13881	26F12 =	partial 4A9 competitor
		27B3
	13878	16H2 =
		20D3 =
		23E7
	13879	22D1
3	13877	22G10	High Endogenous binding, moderate
	13874	17H8 =	293 binding, Calcium insensitive,
		23B6 =	2 sequence clusters, moderate
		28D10	cyno, partial 4A9 competitor,
	13883	25G10	22G10 best binder in bin.
	13875	16C1
4	13590	4610	Low Endogenous and
	13586	4F3	recombinant binding,
	13592	4A2	Calcium sensitive, sequence
	13884	23A10	diverse group, comparable
	13588	2G6	cyno, No 4A9 competition
5	13876	16A4	Best endogenous binder, moderate
			recombinant binder, calcium insensitive,
			very weak cyno, No 4A9 competition.

Of these 18 antibodies. 8 antibodies were selected for further analysis of their epitope binding as described below. At least one representative antibody from each bin was selected for further analysis.

Example 3—Epitope Prediction

Epitope Prediction by 4A9 Antibody Competition and by Human/Mouse Cadherin-19 Chimeras
A 4A9 binding competition method was developed to identify antibodies that compete with 4A9 binding. In 96-well V-bottom plates (Sarstedt #82.1583.001), 50,000 transiently transfected 293T cells were incubated with 5 ug/ml of purified anti-CDH19 antibodies for 1 hr at 4° C. followed by one wash with PBS/2% FBS. 25 μl of 5 μg/ml Alexa647-labelled 4A9 was then added to each well and the plates incubated for 1 hour at 4° C. Cells were then washed two times and the amount of cell associated Alexa647-labelled 4A9 was quantitated by flow cytometry.
The experiments included negative controls consisting of PBS/2% FBS only. The average signal observed in these negative control experiments was adopted as the maximum possible signal for the assay. Antibodies were compared to this maximum signal and a percent inhibition was calculated for each well (% Inhibition=(1-(FL4 Geomean with the anti-CDH19 antibodies/Maximum FL4 Geomean signal)).
Domain binding was determined by flow cytometry as above on 293T cells transiently transfected with plasmids consisting of single or dual human CDH19 cadherin repeat domain replacements into the mouse Cadherin19 backbone cloned into the pTT5 expression vector immediately preceded by native human or murine CDH19 leader sequences and a Flag tag (SEQ ID NO: 968). The experiment included assaying the anti-CDH19 antibodies against mouse Cadherin19 to determine suitability for binning on these human/mouse chimeras.
The data from these experiments are presented in the Table below entitled as follows:

TABLE 3

Calcium Sensitive Binding and Epitope Prediction Summary

Com-

petes

Hu

Mu

Ca2+

with

EC1-

Hu

EC1-

Hu

EC2-

Hu

EC4-

Hu

EC1-

Predicted

Clone

Ab

Sensitive

4A9

5

EC1

2

EC2

3

EC3

5

EC5

5

Epitope

ID

Bin

Binding

(13589)

A

B

C

D

E

F

G

H

I

Region

4A9

13589

1

No

Yes

+

−

44-141

14056

1

No

Yes

+

−

14057

1

No

Yes

+

−

25F8

13880

2

No

Yes

+

−

14094

2

No

Yes

+

−

14096

2

No

Yes

+

−

26D1

13882

2

No

Yes

+

−

14088

2

No

Yes

+

−

17H8

13874

3

No

Yes

+

−

14045

3

No

Yes

+

−

14048

3

No

Yes

+

−

4A2

13592

4

Yes

No

+

−

+

−

250-364

14026

4

Yes

No

+

−

+

−

4610

13590

4

Yes

No

+

−

+

−

14055

4

Yes

No

+

−

+

−

14054

4

Yes

No

+

−

+

−

2G6

13588

4

Yes

No

+

un-

14304

4

Yes

No

+

assignable

14039

4

Yes

No

+

16A4

13876

5

No

+

−

Unassigned

14071

5

No

+

−

complex

epitope

Rat anti-FLAG

+

Legend Table 3

Human and/or murine chimera constructs

A = huCDH19(44-772) (see SEQ ID NO: 944)

B = huCDH19(44-141)::muCDH19(140-770) (see SEQ ID NO: 952)

C = huCDH19(44-249)::muCDH19(248-770) (see SEQ ID NO: 954)

D = muCDH19(44-139)::huCDH19(142-249)::muCDH19(248-770) (see SEQ ID NO: 956)

E = muCDH19(44-139)::huCDH19(142-364)::muCDH19(363-770) (see SEQ ID NO: 958)

F = muCDH19(44-247)::huCDH19(250-364)::muCDH19(363-770) (see SEQ ID NO: 960)

G = muCDH19(44-362)::huCDH19(365-772) (see SEQ ID NO: 962)

H = muCDH19(44-461)::huCDH19(464-772) (see SEQ ID NO: 964)

I = muCDH19(44-770) (see SEQ ID NO: 966)

Epitope Prediction by Human/Chicken Cadherin-19 Chimeras
Domain binding was determined by flow cytometry on 293T cells transiently transfected with plasmids consisting of single human CDH19 cadherin repeat domain replacements into the chicken Cadherin19 backbone cloned into the pTT5 expression vector immediately preceded by native human or chicken CDH19 leader sequences and a Flag tag. The experiment included assaying a subset of anti-CDH19 antibodies against chicken Cadherin19 to determine suitability for binning on these human/chicken chimeras.
The following binding assay was completed in presence of 2 mM CaCl₂). In 96-well V-bottom plates (Costar 3897), 50,000 transiently transfected 293T cells were incubated with 5 ug/ml of purified anti-CDH19 antibodies for 1 hr at 4° C. followed by two washes with PBS/2% FBS. 50 μl of 5 μg/ml Alexa647-labelled anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and 2 ug/ml 7AAD (Sigma A9400) was then added to each well and the plates incubated for 15 minutes at 4° C. Cells were then washed one time and the amount of cell associated Alexa647-labelled Ab was quantitated by flow cytometry. The experiments included mock transfected controls. The data from these experiments are presented in the Table below, n.d.=not determined.

TABLE 4

Antibody Bin C Epitope Prediction Summary

			Hu	Ck					Pre-
			EC1-	Ed1-	Hu	Hu	Hu	Hu	dicted
Clone	Ab.		5	5	EC1	EC2	EC3	EC5	Epitope
ID	ID	Bin	A	J	K	L	M	O	Region

4A9	13589	1	+	−	+	−	−	−	44-141
26F12	13881	2	+	−	+	−	−	−	Bin A
25F8	14096	2	+	−	+	−	−	−
26D1	13882	2	+	−	+	−	−	−
17H8	13874	3	+	−	+	−	−	−
16A4	14071	5	+	−	+	−	−	−
4A2	13592	4	+	−	−	−	+	−	250-
4B10	13590	4	+	−	−	−	+	−	364
2G6	13588	4	+	−	−	−	+	−	Bin B
23A10	14077	4	+	−	−	−	+	−

Rat anti-FLAG	+	+	+	+	+	+	control

+ Positive Binding
− Negative Binding
Legend Table 4
Human and/or chicken chimera constructs
A = huCDH19(44-772) (see SEQ ID NO: 944)
J = ckCDH19(44-776) (see SEQ ID NO: 970)
K = huCDH19(44-141)::ckCDH19(142-776) (see SEQ ID NO: 971)
L = ckCDH19(44-141)::huCDH19(142-249)::ckCDH19(250-776) (see SEQ ID NO: 972)
M = ckCDH19(44-249)::huCDH19(250-364)::ckCDH19(365-776) (see SEQ ID NO: 973)
N = ckCDH19(44-364)::huCDH19(365-463)::ckCDH19(469-776) (see SEQ ID NO: 974)
O = ckCDH19(44-468)::huCDH19(464-772) (see SEQ ID NO: 975)

Epitope Prediction by Macaque/Dog or Rat/Macaque Cadherin-19 Chimeras
Domain binding was determined by flow cytometry on 293T cells transiently transfected with plasmids consisting of rhesus macaque CDH19 cadherin repeat domain 1 or segments domain 1 (designated EC1a, EC1b, EC1c) replacements into the dog Cadherin19 backbone, or rat CDH19 cadherin repeat domain 2 replacement into the rhesus Cadherin19 backbone cloned into the pTT5 expression vector immediately preceded by native rhesus or canine CDH19 leader sequences and a Flag tag. The experiment included assaying a subset of anti-CDH19 antibodies against dog, rat and macaque Cadherin19 to determine suitability for binning on these macaque/dog and rat/rhesus chimeras.
The following binding assay was completed in presence of 2 mM CaCl₂). In 96-well V-bottom plates (Costar 3897), 50,000 transiently transfected 293T cells were incubated with 5 ug/ml of purified anti-CDH19 antibodies for 1 hr at 4° C. followed by two washes with PBS/2% FBS. 50 μl of 5 μg/ml Alexa647-labelled anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and 2 ug/ml 7AAD (Sigma A9400) was then added to each well and the plates incubated for 15 minutes at 4° C. Cells were then washed one time and the amount of cell associated Alexa647-labelled Ab was quantitated by flow cytometry. The experiments included mock transfected controls. The data from these experiments are presented in the Table below, n.d.=not determined.

TABLE 5

Antibody BinA Epitope prediction Summary

			Rh	Ca	rh	rh	rh	ra	Ra	Predicted
			EC1-5	EC1-5	EC1	EC1a	EC1b	EC2	EC1-5	Epitope
Clone ID	Ab. ID	Bin	P	Q	R	S	T	V	W	Region

4A9	13589	1	+	−	+	−	−	−	−	44-141
					+	+	+			Bin A.1
26F12	13881	2	+	−	+	+	+	−	−	44-141
25F8	14096	2	+	−	+	+	+	−	−	Bin A.2
26D1	13882	2	+	−	+	+	+	−	−	(44-
										114)
17H8	13874	3	+	−	+	+	−	−	−	44-141
										Bin A.3
16A4	14071	5	+	−	+	+	−	n.d.	+	(44-65)
4A2	13592	4	+	−	n.d.	n.d.	n.d.	n.d.	+	250-
4B10	13590	4	+	+	n.d.	n.d.	n.d.	n.d.	+	364
2G6	13588	4	+	+	n.d.	n.d.	n.d.	n.d.	+	Bin B
23A10	14077	4	+	+	n.d.	n.d.	n.d.	n.d.	+

Rat anti-FLAG	+	+	+	+	+	+	+

+ Positive Binding
− Negative Binding
(n.d.) Not Determined
Legend Table 5
Rhesus macaque, dog, and/or rat chimera constructs
P = rhCDH19(44-772) (see SEQ ID NO: 976)
Q = caCDH19(44-770) (see SEQ ID NO: 977)
R = rhCDH19(44-141)::caCDH19(141-770) (see SEQ ID NO: 978)
S = rhCDH19(44-65)::caCDH19(65-770) (see SEQ ID NO: 979)
T = caCDH19(44-87)::rhCDH19(89-114)::caCDH19(115-770) (see SEQ ID NO: 980)
U = caCDH19(44-120)::rhCDH19(122-137)::caCDH19(137-770) (see SEQ ID NO: 981)
V = rhCDH19(44-141)::raCDH19(140-247)::rhCDH19(250-772) (see SEQ ID NO: 982)
W = raCDH19(44-770) (see SEQ ID NO: 983)

The data summarized in table 5 allowed for segregating the binder of Bin A 44-141 into the following subgroups:
Bin A.1 44-141
Bin A.2 44-141 (44-114)
Bin A.3 44-141 (44-65)
Epitope Prediction by Rat/Mouse or Human/Mouse Cadherin-19 Chimeras
Domain binding was determined by flow cytometry on 293T cells transiently transfected with plasmids consisting of rat CDH19 cadherin repeat domain 3 substitutions (designated EC3a, EC3b) or human CDH19 cadherin repeat domain 3 substitution (designated EC3c) into the mouse Cadherin19 backbone cloned into the pTT5 expression vector immediately preceded by native mouse CDH19 leader sequence and a Flag tag. The experiment included assaying a subset of anti-CDH19 antibodies against human, rat and mouse Cadherin19 to determine suitability for binning on these rat/mouse and human/mouse chimeras.
The following binding assay was completed in presence of 2 mM CaCl₂). In 96-well V-bottom plates (Costar 3897), 50,000 transiently transfected 293T cells were incubated with 5 ug/ml of purified anti-CDH19 antibodies for 1 hr at 4° C. followed by two washes with PBS/2% FBS. 50 μl of 5 μg/ml Alexa647-labelled anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and 2 ug/ml 7AAD (Sigma A9400) was then added to each well and the plates incubated for 15 minutes at 4° C. Cells were then washed one time and the amount of cell associated Alexa647-labelled Ab was quantitated by flow cytometry. The experiments included mock transfected controls. The data from these experiments are presented in the Table below, n.d.=not determined.

TABLE 6

Antibody Bin B Epitope Prediction Summary

			Hu	Mo	Ra				Pre-
			EC1-	EC1-	EC1-	Ra	Ra	Hu	dicted
Clone	Ab.		5	5	5	EC3c	EC3b	EC3a	Epitope
ID	ID	Bin	A	I	W	X	Y	Z	Region

4A9	13589	1	+	−	−	n.d.	n.d.	n.d.	44-141
26F12	13881	2	+	−	−	n.d.	n.d.	n.d.	Bin A
25F8
	14096	2	+	−	−	n.d.	n.d.	n.d.
26D1	13882	2	+	−	−	n.d.	n.d.	n.d.
17H8	13874	3	+	−	−	n.d.	n.d.	n.d.
16A4	14071	5	+	−	+	n.d.	n.d.	n.d.
4A2	13592	4	+	−	+	+	−	−	250-
									364
4B10	13590	4	+	−	+	+	−	−	(324-
									327)
									Bin B.2
2G6	13588	4	+	+	+	+	+	+	250-364
23A10	14077	4	+	+	+	n.d.	n.d.	n.d.	Bin B.1

Rat anti-	+	+	+	+	+	+	control
FLAG

+ Positive Binding
− Negative Binding
(n.d.) Not Determined
Legend Table 6
Rat/mouse or human/mouse chimera constructs
A = huCDH19(44-772) (see SEQ ID NO: 944)
I = muCDH19(44-770) (see SEQ ID NO: 966)
W = raCDH19(44-770) (see SEQ ID NO: 983)
X = muCDH19(44-323)::raCDH19(324-327)::muCDH19(328-770) (see SEQ ID NO: 984)
Y = muCDH19(44-770)::raCDH19(290, 299, 308) (see SEQ ID NO: 985)
Z = muCDH19(44-770)::huCDH19(271) (see SEQ ID NO: 986)

The data summarized in table 4 allowed for segregating the binder of Bin B 250-364 into the following subgroups:
Bin B.1 250-364
Bin B.2 250-364 (324-327) by rodent numeration as referenced in table 6, corresponding to residues (326-329) within human and macaque CDH19.

Example 4—Hotspot/Covariant Mutants

A total of 18 antibodies were analyzed for potential hotspots and covariance violations. The designed variants (shown below) outline amino acid substitutions capable of reducing and/or avoiding isomerization, deamidation, oxidation, covariance violations, and the like. The 80 engineered variants together with the 15 parental antibodies, thus totaling 95 sequences, were taken forward to the cloning, expression, and purification processes. Site-directed mutagenesis was performed on the engineered variants in a 96-well format. The parental antibodies and engineered variants were expressed by high throughput transient transfection in HEK 293-6E cells, purified using a modified AKTA auto-sampler and assayed for activity and biophysical characteristics. The 3 parental antibodies that had either free (unpaired) Cys or N-glycosylation site were not taken forward in this process. Those were replaced with the engineered version of the parental antibodies. The designed variants outline amino acid substitutions capable of reducing and/or avoiding isomerization, deamidation, oxidation, covariance violations, immunogenicity and the like. It will be appreciated that these variant sequences are examples of engineered antibodies within the meaning of the present application but single point and/or multiple point mutations can be combined in any combinatorial manner in order to arrive at a final desired antigen binding molecule or antibody.

Example 5—CDH19 mRNA Expression Pattern

RNA was extracted from individual patient tissues representing tumor (>70% tumor content by cell count) or normal (0% tumor content by cell count). Individual tissues were homogenized using TisssueLyzer (Qiagen, Valencia, Calif.) and total RNA extracted and purified by the mirVana total RNA extraction kit (Life Technologies, Foster City, Calif.). RNA quality and quantity checked by NanoDrop (NanoDrop, Wilmington, Del.) spectrophotometer readings and Bioanalyzer RNA profiling (Agilient Technologies, Santa Clara, Calif.). RNA was DNAse treated with DNA-free kit (Life Technologies, Foster City, Calif.) and reverse transcribed according to manufacturer's specifications using random hexamers in the High Capacity cDNA Reverse Transcription Kit (Life Technologies, Foster City, Calif.). Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) was performed on cDNA using primers to CDH19, probeset Hs00253534_m1, (Life Technologies, Foster City, Calif.) or the housekeeping gene human ACTB (primers CCT GGC ACC CAG CAC AA; GCC GAT CCA CAC GGA GTA CT; probe ATC AAG ATC ATT GCT CCT CCT GAG CG). 10 μL qRT-PCR reaction components; 1.0 ng/μL cDNA, 2× Universal PCR Master Mix (Life Technologies, Foster City, Calif.), gene expression assay (ACTB; 75 nM primers, 150 nM probe. EPOR; 300 nM primers, 250 nM probe) Following the qRT-PCR amplification program: (1) activation at 50° C. for 2 min; (2) denaturation at 95° C. for 10 min; (3) amplification 40 cycles at 95° C. for 15 s and 60° C. for 1 min with fluorescence capture at each step (ABI PRISM 7900HT Sequence Detection Systems, Applied Biosystems). Threshold cycle values (C_T) were determined, using Sequence Detector software version 2.3 (Applied Biosystems) and transformed to 2^−ΔCTfor relative expression of CDH19 specific transcript to ACTB. The results are shown in FIG. 3. Of 54 unique metastatic and primary melanoma samples, the majority can be seen to overexpress CDH19 mRNA relative to the expression in samples from normal tissue.

Example 6—CDH19 Protein Expression

Expression of CDH19 protein was analyzed in human tumor samples by IHC and the results are shown in FIG. 4. Samples were fixed in 10% neutral buffered formalin for 24 hours, dehydrated and paraffin embedded. 4 μm sections were cut. Sections were deparaffinized first and then heated in DIVA Decloaker solution (Biocare) for 40 minutes for antigen retrieval. Remaining IHC steps were performed at room temperature in a DAKO Autostainer. Sections were incubated for 10 minutes with Peroxidazed 1 (Biocare) to block endogenous peroxidase, followed by incubation for 10 minutes with background sniper (Biocare) to reduce nonspecific background. Section were incubated for 60 minutes with CDH19 antibody (Novo Biologicals, Catalog #H00028513-B01P) at 5 μg/ml, then incubated for 30 minutes with Envision+HRP anti-mouse polymer (DAKO), followed by DAB+(DAKO) for 5 minutes. Sections were counterstained with hematoxylin (DAKO) approximately for 1 minute. CDH19 expression could be detected in 62% of tumors examined (staining intensity ≥1+ in 101 of 162 samples). 51% of the tumor samples demonstrated medium to high expression (staining intensity of 2+ to 3+ in 83 of 162 samples). CDH19 showed dense and distinct membrane staining in many samples, although in some tumors heterogeneity was noted.

Example 7—Selection of Model Cell Lines

Tumor cell lines were analyzed by flow cytometry and IHC to identify model systems with CDH19 expression similar to human tumors. Human anti-huCDH19 IgG4 antibody 4A2 was purified directly from hybridoma conditioned media. For flow cytometry, 2×10⁵cells were incubated with 200 nM of the CDH19 4A2 antibody that was conjugated to PE at a 1:1 ratio. The incubation and subsequent wash steps were performed in the presence of 1.2 mM calcium. A tube of QuantiBRITE PE lyophilized beads with four levels of PE (BD, cat #340495) was simultaneously prepared according to the manufacturer's instructions. The beads were analyzed by flow cytometry to generate a standard curve. The PE median values obtained from the melanoma lines after FACS analysis were then calibrated against the standard curve to calculate the antibodies bound per cell (ABC), which provides an estimate of the number of receptors on each cell. IHC was performed as described in Example 6 and the results are provided in FIG. 5. The melanoma cell line CHL-1 expresses about 10,000 CDH19 molecules on the cell surface, while Colo699 cells express about 5,000 receptors. Both cell lines represent tumors with medium to high expression levels based on IHC. Expression in A2058 is very low, while LOX cells do not express any detectable CDH19 protein.

Example 8—Preparation of Antibody Drug Conjugates

DNA sequences encoding the heavy chain and light chain components of anti-CDH19 antibodies were subcloned into mammalian expression vector pTT5 and transiently co-transfected into 293-6E cells, as described in published US2005/0170450 which is incorporated in its entirety by reference. Antibodies were purified from conditioned media by protein A affinity and ion exchange chromatography. Antibodies were incubated at 3 to 5 mg/ml with 4 to 13 equivalents of SMCC-DM1 in neutral to slightly basic buffered solutions containing 50 mM sodium chloride, 2 mM EDTA, and from 5 to 15% dimethylacetamide at room temperature for up to 5 hours or at 4° C. for up to 18 hours. Conjugation to DM1 and DAR determination for conjugates, is described in U.S. Pat. No. 7,368,565 and related U.S. Pat. No. 7,851,432, which are herein incorporated in their entirety by reference. Resultant antibody drug conjugates (ADCs) were purified from solutes and unconjugated drug by gel permeation or ion exchange chromatography. UV spectrophotometric measurements at 252 nm and 280 nm combined with respective molar extinction coefficients of SMCC-DM1 and antibody as defined by amino acid composition were used to algebraically determine the concentration of drug (CD) and antibody (CAb) components of ADC preparations which could be used to calculate a drug to antibody ratio (DAR) as described in U.S. Pat. No. 7,368,565. DAR determinations of ADCs were more accurately made by similar algebraic calculations based on integrated peaks measured at 252 nm and 280 nm in analytical size exclusion chromatography. Orthogonal LC/MS methods were also used to qualitatively assess random drug distribution profiles by mass. The table below describes ADCs used in the experiments for which the results are provided in FIG. 6 (lots 1,2), FIG. 7 (lots 3-10), and FIG. 8 (lots 11-14), which are representative of typical ADC preparations.


Exam-	ADC
ple	lot	ID	hu anti-huCDH19 IgG1 antibody	DAR

Fig. 6	1	13590	4B10	3.6
Fig. 6	2	1462	anti-SA (anti-streptavidin control)	4.5
Fig. 7	3	13590	4B10	2.5
Fig. 7	4	13590	4B10	4.1
Fig. 7	5	13590	4B10	5.1
Fig. 7	6	13590	4B10	5.8
Fig. 7	7	13590	4B10	5
Fig. 7	8	13590	4B10	6.3
Fig. 7	9	13590	4B10	7.4
Fig. 7	10	1462	anti-SA (anti-streptavidin control)	6.5
Fig. 8	11	14096	25F8.1 (K45Q,S102A,D111E)	5.6
			VL + (F90Y) VH
Fig. 8	12	14045	17H8.2 (G149R) VL	4.7
Fig. 8	13	14054	4B10 (H450,A90T) VL +	5.2
			(R17G) VH
Fig. 8	14	1462	anti-SA (anti-streptavidin control)	5.3

Example 9—Activity of CDH19 Targeting ADCs in Model Cell Lines

The CDH19 recognizing parental antibody 4B10 (Ab ID 13590) was covalently coupled to the toxin DM1 as described in Example 8. The tumor cells were plated in 384-well microtiter plates on Day 1, and on Day 2, the ADC was titrated on the cells and incubated for additional 72 h. Cell viability was determined at the end of the experiment with CellTiterGlo reagent (Promega) according to the manufacturer's instructions. Unconjugated, free DM1 served as a positive control, and a streptavidin recognizing antibody/DM1 conjugate served as a negative control to detect non specific binding. IC50s were determined with a non-linear, 4 parameter curve fit and are shown in FIG. 6.

Example 10—Effect of Drug to Antibody Ratio (DAR) on ADC Potency

In order to assess the effect of the drug antibody ratio on the potency of the ADC molecule, the CDH19 recognizing parental antibody 4B10 (Ab ID 13590) was coupled with different amounts of DM1 as indicated in FIG. 7. The effect of DARs on ADC potency was determined in cell viability assays as described in Example 9. An increased DAR leads to increases in potency for a given DM1 concentration. This effect is more pronounced on tumor cells with lower CDH19 expression.

Example 11—Efficacy of CDH19 Targeting ADCs In Vivo

Three CDH19 recognizing engineered variant antibodies ( Ab IDs 14096, 14045, 14054) were coupled to DM1 and tested in xenograft experiments. CHL-1 cells were suspended in a solution of 50% serum free medium and 50% Matrigel, and implanted subcutaneously in the flank of female athymic nude mice. Each mouse received five million cells in a volume of 200 μl. When tumors reached approximately 200 mm³, mice were sorted into seven groups of 10 mice each with equivalent mean and SD tumor size per group, and dosed with test agents or controls. All treatments were administered IV in a volume of 200 μl. Tumors were measured two times per week using calipers. Length, width and height measurements were taken A repeated measures ANOVA with Dunnett's post-hoc test was used to compare the difference in tumor volume between each CDH19 targeting ADC and a non-specific control ADC (anti-streptavidin coupled to DM1). The percentage of tumor growth inhibition was calculated for each CDH19 targeting ADC compared to the corresponding unconjugated antibody. All three reagents demonstrate significant inhibition of tumor growth in mice as shown in FIG. 8.

Example 12—Internalization of CDH19 Following ADC Binding

Human anti-huCDH19 IgG4 antibody 4A2 was purified directly from hybridoma conditioned media and conjugated with SMCC-DM1 as described in example 8. Because the exact sequence of parental 4A2 was unknown at the time, the DAR of this IgG4 ADC was estimated to be 4.4 using a molecular weight of 150,000 Da and an extinction coefficient of 225,000 at 280 nm. CHL-1 melanoma cells were incubated with either unconjugated or DM1 conjugated CDH19 recognizing parental antibody 4A2 in complete medium at 4° C. or for 2 h at 37° C. After a brief wash in PBS, cells were fixed in 3% formaldehyde/PBS for 20 min. Fixed cells were washed, blocked and permeabilized in TBST/1% BSA/5% normal donkey serum/0.3% TX-100 and incubated with rabbit anti-EEA1 (CST #3288). Following another wash step, the samples were incubated with donkey anti mouse Alexa 488 and donkey anti rabbit Alexa 554. Images were taken with a 63× oil lens on a Zeiss LSM 510 confocal microscope. A review of the images demonstrate that both the parental and DM1 conjugated antibody detect the membrane bound CDH19 at 4° C. but get quickly internalized and co-localize with endosome markers at 37° C. Thus, both the unconjugated and DM1 conjugated CDH19 antibodies are internalized by melanoma cells, and the conjugation of the drug does not appear to interfere with the internalization of the CDH19 antibody.

Example 13—Efficacy of CDH19 Targeting ADCs In Vivo

13.1: 4B10-DM1 Moderately Inhibited Tumor Growth at 182 μg/kg DM1 in CHL-1 Xenografts
A study was conducted to examine the effect of the anti-CDH19 ADC 4B10-DM1 administered once per week for two weeks in CHL-1 xenografts. CHL-1 cells were suspended in a solution of 50% serum free medium and 50% Matrigel, and implanted subcutaneously in the flank of female athymic nude mice. Each mouse received five million cells in a volume of 200 μl. When tumors reached approximately 150 mm3, mice were sorted into groups of 10 mice each with equivalent mean and SD tumor size per group and dosed with test agents or controls. All treatments were administered IV in a volume of 200 μl. Tumors were measured two times per week using calipers (length, width and height measurement). Body weights were recorded at each measurement. A repeated measures ANOVA with Dunnett's post-hoc test was used to compare the difference in tumor volume between mice treated with 4B10-DM1 and the ADC control. The percentage of tumor growth inhibition was calculated against the ADC control. The results are shown in FIG. 9.
13.2: Increasing the DAR Did not Increase Tumor Growth Inhibition in CHL-1 Xenografts
A study was conducted to examine the effect of drug:antibody ratio (DAR) on efficacy of the anti-CDH19 ADC 4B10-DM1 administered once per week for two weeks in CHL-1 xenografts. CHL-1 cells were suspended in a solution of 50% serum free medium and 50% Matrigel, and implanted subcutaneously in the flank of female athymic nude mice. Each mouse received five million cells in a volume of 200 μl. When tumors reached approximately 200 mm3, mice were sorted into groups of 10 mice each with equivalent mean and SD tumor size per group and dosed with test agents or controls. All treatments were administered IV in a volume of 200 μl. Tumors were measured two times per week using calipers (length, width and height measurement). Body weights were recorded at each measurement. A repeated measures ANOVA with Dunnett's post-hoc test was used to compare the difference in tumor volume between mice treated with 4B10-DM1 and the ADC control. The percentage of tumor growth inhibition was calculated against the ADC control. The results are shown in FIG. 10.
13.3: Anti-CDH19 ADCs Moderately Inhibited Tumor Growth in COLO699 Xenografts
A study was conducted to examine the effects of anti-CDH19 ADC 4B10-DM1 and an optimized variant administered once per week for two weeks on COLO699 xenografts. COLO699 cells were suspended in a solution of 50% serum free medium and 50% Matrigel, and implanted subcutaneously in the flank of female athymic nude mice. Each mouse received five million cells in a volume of 200 μl. When tumors reached approximately 200 mm3, mice were sorted into groups of 10 mice each with equivalent mean and SD tumor size per group, and dosed with test agents or controls. All treatments were administered IV in a volume of 200 μl. Tumors were measured two times per week using calipers (length, width and height measurement). Body weights were recorded at each measurement. A repeated measures ANOVA with Dunnett's post-hoc test was used to compare the difference in tumor volume between mice treated with 4B10-DM1 and the ADC control. The percentage of tumor growth inhibition was calculated against the ADC control. A similar study was conducted as described above (data not shown) that resulted in the same trends for tumor growth inhibition, however, that study did not reach statistical significance. The results are shown in FIG. 11.
Sequence Table:

TABLE Ia

HEAVY CHAIN CDRs

Ab	Type	CDR 1	CDR 2	CDR 3

1D10	NA	AGCTATGGCATGCAC	GTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
2C12			AATAAATACTATGCAGACTCC	TACAGGCTACTACTACGGTA
			GTGAAGGGC	TGGACGTC
		SEQ ID NO: 1	SEQ ID NO: 2	SEQ ID NO: 3
	AA	SYGMH	VIWYDGSNKYYADSVKG	RAGIIGTTGYYYGMDV
		SEQ ID NO: 4	SEQ ID NO: 5	SEQ ID NO: 6

1F10	NA	AGTGGTGGTTACTACT	TACATCTATTACAGTGGGAGC	GATGGAAGCAGTGGCTGGTA
		GGAGC	ACCTACTACAACCCGTCCCTC	CTTCCAGCAC
			ACGAGT
		SEQ ID NO: 7	SEQ ID NO: 8	SEQ ID NO: 9
	AA	SGGYYWS	YIYYSGSTYYNPSLTS	DGSSGWYFQH
		SEQ ID NO: 10	SEQ ID NO: 11	SEQ ID NO: 12

2C12_LC#1	NA	AGCTATGGCATGCAC	GTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
			AATAAATACTATGCAGACTCC	TACAGGCTACTACTACGGTA
			GTGAAGGGC	TGGACGTC
		SEQ ID NO: 13	SEQ ID NO: 14	SEQ ID NO: 15
	AA	SYGMH	VIWYDGSNKYYADSVKG	RAGIIGTTGYYYGMDV
		SEQ ID NO: 16	SEQ ID NO: 17	SEQ ID NO: 18

2G6_LC#1	NA	AGCTATGGCATGCAC	TTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
			AATAAATACTATGCAGACTCC	TATAGGCTACTACTACGGTA
			GTGAAGGAC	TGGACGTC
		SEQ ID NO: 19	SEQ ID NO: 20	SEQ ID NO: 21
	AA	SYGMH	FIWYDGSNKYYADSVKD	RAGIIGTIGYYYGMDV
		SEQ ID NO: 22	SEQ ID NO: 23	SEQ ID NO: 24

2G6	NA	AGCTATGGCATGCAC	TTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
			AATAAATACTATGCAGACTCC	TATAGGCTACTACTACGGTA
			GTGAAGGAC	TGGACGTC
		SEQ ID NO: 25	SEQ ID NO: 26	SEQ ID NO: 27
	AA	SYGMH	FIWYDGSNKYYADSVKD	RAGIIGTIGYYYGMDV
		SEQ ID NO: 28	SEQ ID NO: 29	SEQ ID NO: 30

2H12	NA	AGCTATGGCATGCAC	GTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
			AATAAATACTATACAGACTCC	TACAGGCTACTACTACGGTA
			GTGAAGGGC	TGGACGTC
		SEQ ID NO: 31	SEQ ID NO: 32	SEQ ID NO: 33
	AA	SYGMH	VIWYDGSNKYYTDSVKG	RAGIIGTTGYYYGMDV
		SEQ ID NO: 34	SEQ ID NO: 35	SEQ ID NO: 36

2H12_LC#2	NA	AGCTATGGCATGCAC	GTTATATGGTATGATGGAAGT	AGGGCCGGTATAATAGGAAC
			AATAAATACTATACAGACTCC	TACAGGCTACTACTACGGTA
			GTGAAGGGC	TGGACGTC
		SEQ ID NO: 37	SEQ ID NO: 38	SEQ ID NO: 39
	AA	SYGMH	VIWYDGSNKYYTDSVKG	RAGIIGTTGYYYGMDV
		SEQ ID NO: 40	SEQ ID NO: 41	SEQ ID NO: 42

4A2	NA	AGTAGTGGTTACTACT	TACATCTATTACACTGGGAGC	GATGGAAGCAGTGGCTGGTA
5B4		GGAGC	GCCTACTACAACCCGTCCCTC	CTTCCAGTAT
5C5			AAGAGT
		SEQ ID NO: 43	SEQ ID NO: 44	SEQ ID NO: 45
	AA	SSGYYWS	YIYYTGSAYYNPSLKS	DGSSGWYFQY
		SEQ ID NO: 46	SEQ ID NO: 47	SEQ ID NO: 48

4A9	NA	GGTTACTACTGGAGC	TATTTCTCTTACAGTGGGAGC	AACTGGGCCTTCCACTTTGA
			ACCAACTACAACCCCTCCCTC	CTTC
			AAGAGT
		SEQ ID NO: 49	SEQ ID NO: 50	SEQ ID NO: 51
	AA	GYYWS	YFSYSGSTNYNPSLKS	NWAFHFDF
		SEQ ID NO: 52	SEQ ID NO: 53	SEQ ID NO: 54

4B10	NA	AGCTATGACATGCAC	GTTATATCATATGATGGAACT	GAACGATATTTTGACTGGTC
4C2			AATGAATACTATGCAGACTCC	TTTTGACTAC
			GTGAAGGGC
		SEQ ID NO: 55	SEQ ID NO: 56	SEQ ID NO: 57
	AA	SYDMH	VISYDGTNEYYADSVKG	ERYFDWSFDY
		SEQ ID NO: 58	SEQ ID NO: 59	SEQ ID NO: 60

4D2	NA	AGTTATGACATGCAC	GTTATATCATATGATGGAACT	GAACGATATTTTGACTGGTC
			AATGAATACTATGCAGACTCC	TTTTGACTAC
			GTGAAGGGC
		SEQ ID NO: 61	SEQ ID NO: 62	SEQ ID NO: 63
	AA	SYDMH	VISYDGTNEYYADSVKG	ERYFDWSFDY
		SEQ ID NO: 64	SEQ ID NO: 65	SEQ ID NO: 66

4D3	NA	AGCTATGACATGGAC	GTTATATGGTATGATGGAAGT	GAAACTGGGGAGGgCTGGTA
4F3			AATAAAtacTATGCAGACTCC	CTTCGAtctc
			GTGAGGGGC
		SEQ ID NO: 67	SEQ ID NO: 68	SEQ ID NO: 69
	AA	SYDMD	VIWYDGSNKYYADSVRG	ETGEGWYFDL
		SEQ ID NO: 70	SEQ ID NO: 71	SEQ ID NO: 72

4E10	NA	AGCTATGACATGCAC	GTTATATGGTATGATGGAAGT	GAGTATAGGTACAGCTGGTA
			AATAAATACTATGCAGACTCC	CTTTGACTAC
			GTGAAGGGC
		SEQ ID NO: 73	SEQ ID NO: 74	SEQ ID NO: 75
	AA	SYDMH	VIWYDGSNKYYADSVKG	EYRYSWYFDY
		SEQ ID NO: 76	SEQ ID NO: 77	SEQ ID NO: 78

4F7	NA	AGTTACTCCTGGAGC	TATATCTATTACAGTGGGAGC	AACTGGGCCTTCCACTTTGA
			ACCAACTACAACCCCTCCCTC	CTAC
			AAGAGT
		SEQ ID NO: 79	SEQ ID NO: 80	SEQ ID NO: 81
	AA	SYSWS	YIYYSGSTNYNPSLKS	NWAFHFDY
		SEQ ID NO: 82	SEQ ID NO: 83	SEQ ID NO: 84

5E3	NA	AGCTATAGCATGCAC	TCCATTAGTAGTAGTAGTAGT	GGGGAAACTGGAACTAACTA
			TACATATACTACGCAGACTCA	CTACTACTACGGTATGGACG
			GTGAAGGGC	TC
		SEQ ID NO: 85	SEQ ID NO: 86	SEQ ID NO: 87
	AA	SYSMH	SISSSSSYIYYADSVKG	GETGTNYYYYGMDV
		SEQ ID NO: 88	SEQ ID NO: 89	SEQ ID NO: 90

17H8	NA	AGTTACTACTGGAGC	TATATCTATTACATTGGGAGC	GATTCCCGGTATAGAAGTGG
23B6			ACCAACTACAACCCCTCCCTC	CTGGTACGATGCTTTTGATA
28D10			AAGAGT	TC
		SEQ ID NO: 91	SEQ ID NO: 92	SEQ ID NO: 93
	AA	SYYWS	YIYYIGSTNYNPSLKS	DSRYRSGWYDAFDI
		SEQ ID NO: 94	SEQ ID NO: 95	SEQ ID NO: 96

16C1	NA	GGTTACTACTGGAGC	TATATCTATTACATTGGGAGC	GATGGGAGCAGTGGCTGGTA
			ACCAACTACAACCCCTCCCTC	CCGGTGGTTCGACCCC
			AAGAGT
		SEQ ID NO: 97	SEQ ID NO: 98	SEQ ID NO: 99
	AA	GYYWS	YIYYIGSTNYNPSLKS	DGSSGWYRWFDP
		SEQ ID NO: 100	SEQ ID NO: 101	SEQ ID NO: 102

16A4	NA	AGTTACTACTGGAGC	TATATCTATTACAGTGGGAGC	GATCAAAGGCGGATAGCAGC
			ACCAATTACAACCCCTCCCTC	AGCTGGTACCCACTTCTACG
			AAGAGT	GTATGGACGTC
		SEQ ID NO: 103	SEQ ID NO: 104	SEQ ID NO: 105
	AA	SYYWS	YIYYSGSTNYNPSLKS	DQRRIAAAGTHFYGMDV
		SEQ ID NO: 106	SEQ ID NO: 107	SEQ ID NO: 108

16E2	NA	AGCTATGGCATGCAC	GTGATATGGTATGATGGAAGT	GACGGGTGGGAGCTGTCCTT
17E10			AATAAATACTATGCAGACTCC	TGACTAC
20B12			GTGAAGGGC
		SEQ ID NO: 109	SEQ ID NO: 110	SEQ ID NO: 111
	AA	SYGMH	VIWYDGSNKYYADSVKG	DGWELSFDY
		SEQ ID NO: 112	SEQ ID NO: 113	SEQ ID NO: 114

22G10	NA	AGTTATGCCATGAAC	ACTATTAGTGGTGGTGGTGCT	GGGGGAATGGGGGGATACTA
			AACACATACTACGCAGACTCC	CTACGGTATGGACGTC
			GTGAAGGGC
		SEQ ID NO: 115	SEQ ID NO: 116	SEQ ID NO: 117
	AA	SYAMN	TISGGGANTYYADSVKG	GGMGGYYYGMDV
		SEQ ID NO: 118	SEQ ID NO: 119	SEQ ID NO: 120

16H2	NA	AGCTACTTTATTCAC	ATAATCAACCCTATTAGTGTT	GGGGGGATACAGCTATGGTT
20D3			AGCACAAGCTACGCACAGAAG	ACATTTTGACTAC
23E7			TTCCAGGGC
		SEQ ID NO: 121	SEQ ID NO: 122	SEQ ID NO: 123
	AA	SYFIH	IINPISVSTSYAQKFQG	GGIQLWLHFDY
		SEQ ID NO: 124	SEQ ID NO: 125	SEQ ID NO: 126

22D1	NA	AGCTACTTTATTCAC	ATAATCAACCCTATTAGTGTT	GGGGGGATACAGCTATGGTT
			AGCACAAGCTACGCACAGAAG	ACATTTGGACTAC
			TTCCAGGGC
		SEQ ID NO: 127	SEQ ID NO: 128	SEQ ID NO: 129
	AA	SYFIH	IINPISVSTSYAQKFQG	GGIQLWLHLDY
		SEQ ID NO: 130	SEQ ID NO: 131	SEQ ID NO: 132

25F8	NA	AGCTACTATATTCAC	ATAATCAACCCCAGTGGTGGT	GGGGGAATACAGCTATGGTT
			AGCACAAGGTACGCACAGAAG	ACATTttGACTAC
			TTCCAGGGC
		SEQ ID NO: 133	SEQ ID NO: 134	SEQ ID NO: 135
	AA	SYYIH	IINPSGGSTRYAQKFQG	GGIQLWLHFDY
		SEQ ID NO: 136	SEQ ID NO: 137	SEQ ID NO: 138

26F12	NA	AACTACTATATGTCC	ATAATCAACCCTAGTGGTGGT	GGGGGGATACAACTATGGTT
27B3			GACTCAACCTACGCACAGAAG	ACATTTTGACTAC
			TTCCAGGGC
		SEQ ID NO: 139	SEQ ID NO: 140	SEQ ID NO: 141
	AA	NYYMS	IINPSGGDSTYAQKFQG	GGIQLWLHFDY
		SEQ ID NO: 142	SEQ ID NO: 143	SEQ ID NO: 144

26D1	NA	AGCTACTATATGTCC	ATAATCCACCCTAGTGGTGGT	GGGGGGATAAAACTATGGTT
			GACACAACCTACGCACAGAAG	ACATTTTGACTAT
			TTCCAGGGC
		SEQ ID NO: 145	SEQ ID NO: 146	SEQ ID NO: 147
	AA	SYYMS	IIHPSGGDTTYAQKFQG	GGIKLWLHFDY
		SEQ ID NO: 148	SEQ ID NO: 149	SEQ ID NO: 150

25G10	NA	GGTTACTACTGGAGC	TATATCTATTACATTGGGAGC	GATGGGAGCAGTGGCTGGTA
			ACCAACTACAACCCCTCCCTC	CCGGTGGTTCGACCCC
			AAGAGT
		SEQ ID NO: 151	SEQ ID NO: 152	SEQ ID NO: 153
	AA	GYYWS	YIYYIGSTNYNPSLKS	DGSSGWYRWFDP
		SEQ ID NO: 154	SEQ ID NO: 155	SEQ ID NO: 156

23A10	NA	CGCTATGGCATACAC	GTTATATGGTATGATGGAAGT	AGGGCCGGTATACCTGGAAC
			AATAAATACTATGCAGACTCC	TACGGGCTACTACTATGGTA
			GTGAAGGGC	TGGACGTC
		SEQ ID NO: 157	SEQ ID NO: 158	SEQ ID NO: 159
	AA	RYGIH	VIWYDGSNKYYADSVKG	RAGIPGTTGYYYGMDV
		SEQ ID NO: 160	SEQ ID NO: 161	SEQ ID NO: 162

19B5	NA	AGCTACTTTATTCAC	ATTATCAACCCTATTAGTGTT	GGGGGGATACAGCTATGGTT
			AGCACAAGCTACGCACAGAAG	ACATTTGGACTAC
			TTCCAGGGC
		SEQ ID NO: 163	SEQ ID NO: 164	SEQ ID NO: 165
	AA	SYFIH	IINPISVSTSYAQKFQG	GGIQLWLHLDY
		SEQ ID NO: 166	SEQ ID NO: 167	SEQ ID NO: 168

TABLE Ib

LIGHT CHAIN CDRs

Ab	Type	CDR 1	CDR 2	CDR 3

1D10	NA	TCTGGAGATAGATTGG	CAAGATACCAAGCGGCCCTCA	CAGGCGTGGGACAGCAGCAC
2C12		GGGAAAAATATACTTG		TGTGGTA
		C
		SEQ ID NO: 169	SEQ ID NO: 170	SEQ ID NO: 171
	AA	SGDRLGEKYTC	QDTKRPS	QAWDSSTVV
		SEQ ID NO: 172	SEQ ID NO: 173	SEQ ID NO: 174

1F10	NA	AGGGCCAGTCGGAGTA	GGTCCATCCAGCAGGGCCACT	CAGCAGTATGGTAGCTCATT
		TTAGCAGCAGCTACTT		CACT
		AGCC
		SEQ ID NO: 175	SEQ ID NO: 176	SEQ ID NO: 177
	AA	RASRSISSSYLA	GPSSRAT	QQYGSSFT
		SEQ ID NO: 178	SEQ ID NO: 179	SEQ ID NO: 180

2C12_LC#1	NA	AGGtCTAGTCAAAGcc	AAGGTTTCTAACTGGGactct	ATGCAAGGTATAGTGTGGCC
		tcgtaTACAGTGATGG		GTGCAGT
		AAACAcctACTTGAAT
		SEQ ID NO: 181	SEQ ID NO: 182	SEQ ID NO: 183
	AA	RSSQSLVYSDGNTYLN	KVSNWDS	MQGIVWPCS
		SEQ ID NO: 184	SEQ ID NO: 185	SEQ ID NO: 186

2G6_LC#1	NA	AGGTCTAGTCAAAGCC	CAGGTTTCTAACTGGGACTCT	ATGCAAGATACACTGTGGCC
		TCGTATACAGTGATGG		GTGCAGT
		AAACACCTACTTGAAT
		SEQ ID NO: 187	SEQ ID NO: 188	SEQ ID NO: 189
	AA	RSSQSLVYSDGNTYLN	QVSNWDS	MQDTLWPCS
		SEQ ID NO: 190	SEQ ID NO: 191	SEQ ID NO: 192

2G6	NA	TCTGGAGATAGGTTGG	CAAGATACCAAGCGGCCCTCA	CAGGCGTGGGACAGCAGCAC
		GGGAAAAATATACTTG		TGTGGTA
		C
		SEQ ID NO: 193	SEQ ID NO: 194	SEQ ID NO: 195
	AA	SGDRLGEKYTC	QDTKRPS	QAWDSSTVV
		SEQ ID NO: 196	SEQ ID NO: 197	SEQ ID NO: 198

2H12	NA	TCTGGAGATAGATTGG	CAAGATACCAAGCGGCCCTCA	CAGGCGTGGGACAGCAGCAC
		GGGAAAAATATACTTG		TGTGGTA
		C
		SEQ ID NO: 199	SEQ ID NO: 200	SEQ ID NO: 201
	AA	SGDRLGEKYTC	QDTKRPS	QAWDSSTVV
		SEQ ID NO: 202	SEQ ID NO: 203	SEQ ID NO: 204

2H12_LC#2	NA	AGGTCTAGTCAAAGCC	AAGGTTTCTAACTGGGACTCT	ATGCAAGATACACTGTGGCC
		TCGTATACAGTGATGG		GTGCAGT
		AAACACCTACTTGAAT
		SEQ ID NO: 205	SEQ ID NO: 206	SEQ ID NO: 207
	AA	RSSQSLVYSDGNTYLN	KVSNWDS	MQDTLWPCS
		SEQ ID NO: 208	SEQ ID NO: 209	SEQ ID NO: 210

4A2	NA	AGGgcCAGTCGGAATA	GGTCCATCCAGCAGGGccaCT	CAGCAGTATGGtagctCATT
5B4		TTAGCAGCAGCTACtt		CACT
5C5		aGCC
		SEQ ID NO: 211	SEQ ID NO: 212	SEQ ID NO: 213
	AA	RASRNISSSYLA	GPSSRAT	QQYGSSFT
		SEQ ID NO: 214	SEQ ID NO: 215	SEQ ID NO: 216

4A9	NA	ACTGGGAGCAGCTCCA	GGTAACAACAATCGGCCCTCA	CAGTCCTATGACAGCagACT
		ACATCGGGACAGGTTA		GAGTGGTTGGGTG
		TGCTGTACAC
		SEQ ID NO: 217	SEQ ID NO: 218	SEQ ID NO: 219
	AA	TGSSSNIGTGYAVH	GNNNRPS	QSYDSRLSGWV
		SEQ ID NO: 220	SEQ ID NO: 221	SEQ ID NO: 222

4B10	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGCCACT	CAGCAGTACAGTAACTCgtg
4C2		TTAGCAACACCTACTT		GACG
		AGCC
		SEQ ID NO: 223	SEQ ID NO: 224	SEQ ID NO: 225
	AA	RASQSVSNTYLA	GASSRAT	QQYSNSWT
		SEQ ID NO: 226	SEQ ID NO: 227	SEQ ID NO: 228

4D2	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGCCGCT	CagcagTATAGTAacTcgtg
		TTAGCAACACCTACTT	GACG
	AGCC
		SEQ ID NO: 229	SEQ ID NO: 230	SEQ ID NO: 231
	AA	RASQSVSNTYLA	GASSRAA	QQYSNSWT
		SEQ ID NO: 232	SEQ ID NO: 233	SEQ ID NO: 234

4D3	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGCCACT	CAGCAGTATGGTAGCTCGTG
4F3		TTAGCAGCAGCTACTT		GACG
		AGCC
		SEQ ID NO: 235	SEQ ID NO: 236	SEQ ID NO: 237
	AA	RASQSVSSSYLA	GASSRAT	QQYGSSWT
		SEQ ID NO: 238	SEQ ID NO: 239	SEQ ID NO: 240

4E10	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGTCACT	CAGCAATATAGTAACTCGTG
		TTGGCAGCAGCTACTT		GACG
		AGCC
		SEQ ID NO: 241	SEQ ID NO: 242	SEQ ID NO: 243
	AA	RASQSVGSSYLA	GASSRVT	QQYSNSWT
		SEQ ID NO: 244	SEQ ID NO: 245	SEQ ID NO: 246

4F7	NA	ACTGGGAGCAGCTCCA	GGTAACAGCAATCGGCCCTCA	CAGTCCTATGACAGCAGTCT
		ATATCGGGACAGGTTA		GAGTGGTTGGGTG
		TGATGTACAC
		SEQ ID NO: 247	SEQ ID NO: 248	SEQ ID NO: 249
	AA	TGSSSNIGTGYDVH	GNSNRPS	QSYDSSLSGWV
		SEQ ID NO: 250	SEQ ID NO: 251	SEQ ID NO: 252

5E3	NA	TCTGGAGATAAATTGG	CAAGATAGCAAGCGGCCCTCA	CAGGCGTGGGACAGCAGCAC
		GGGATGAATATGCTTG		TGTGGTA
		C
		SEQ ID NO: 253	SEQ ID NO: 254	SEQ ID NO: 255
	AA	SGDKLGDEYAC	QDSKRPS	QAWDSSTVV
		SEQ ID NO: 256	SEQ ID NO: 257	SEQ ID NO: 258

17H8	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGCCACT	CAGCAGTATGGTAAATCACC
23B6		TTGCCGGCAGCTACCT		GATCACC
28D10		AGCC
		SEQ ID NO: 259	SEQ ID NO: 260	SEQ ID NO: 261
	AA	RASQSVAGSYLA	GASSRAT	QQYGKSPIT
		SEQ ID NO: 262	SEQ ID NO: 263	SEQ ID NO: 264

16C1	NA	AGGGCCAGCCAGAGTG	GGTGCATCCAGCAGGGCCACT	CAGCAGTATGGTAACTCACC
		TTAGCAGCAGCTACTT		GCTCACT
		AGCC
		SEQ ID NO: 265	SEQ ID NO: 266	SEQ ID NO: 267
	AA	RASQSVSSSYLA	GASSRAT	QQYGNSPLT
		SEQ ID NO: 268	SEQ ID NO: 269	SEQ ID NO: 270

16A4	NA	AGGGCCAGTCAGAGTG	GGTACATCCAGCAGGGCCACT	CAGCAGTACGGTAGCTCACC
		TTAGCAGCAGTTATTT		TTTCACT
		AGCC
		SEQ ID NO: 271	SEQ ID NO: 272	SEQ ID NO: 273
	AA	RASQSVSSSYLA	GTSSRAT	QQYGSSPFT
		SEQ ID NO: 274	SEQ ID NO: 275	SEQ ID NO: ***276

16E2	NA	CGGGCGAGTCAGGGCA	GCTGCATCCAGTTTGCAAAGT	CAACACTATTTTACTTACCC
17E10		TTAGCAATTATTTAGC		TCGGACG
20B12		C
		SEQ ID NO: 277	SEQ ID NO: 278	SEQ ID NO: 279
	AA	RASQGISNYLA	AASSLQS	QHYFTYPRT
		SEQ ID NO: 280	SEQ ID NO: 281	SEQ ID NO: 282

22G10	NA	AGGGCCAGTCAGAGTA	GGTGCATTTACCAGGGCCACT	CAGCAGTATAATTACTGGCC
		TTAGCAGCAACTTAGC		GCTCACT
		C
		SEQ ID NO: 283	SEQ ID NO: 284	SEQ ID NO: 285
	AA	RASQSISSNLA	GAFTRAT	QQYNYWPLT
		SEQ ID NO: 286	SEQ ID NO: 287	SEQ ID NO: 288

16H2	NA	TCTGGAAGCAGCTCCA	ACTAATAATCAGCGGCCCTCA	GCAACATGGGATGACAGCCT
20D3		ACATCGGAAGTAATTT		GAATGGTTGGGTG
23E7		TGTAAAC
		SEQ ID NO: 289	SEQ ID NO: 290	SEQ ID NO: 291
	AA	SGSSSNIGSNFVN	TNNQRPS	ATWDDSLNGWV
		SEQ ID NO: 292	SEQ ID NO: 293	SEQ ID NO: 294

22D1	NA	TCTGGAAGCAGCTCCA	ACTAATAATCAGCGGCCCTCA	GCAACATGGGATGACAGTAT
		ACATCGGAAGCAATTT		GAATGGTTGGGTG
		TGTAAAC
		SEQ ID NO: 295	SEQ ID NO: 296	SEQ ID NO: 297
	AA	SGSSSNIGSNFVN	TNNQRPS	ATWDDSMNGWV
		SEQ ID NO: 298	SEQ ID NO: 299	SEQ ID NO: 300

25F8	NA	TCTGGAAGCAGCTCCA	ACTAATAATCAGCGGCCCTCA	GCAGCATGGGATGACAGCCT
		ACATCGGAAGGAATTT		GAATGGTTGGGTG
		TGTAAAC
		SEQ ID NO: 301	SEQ ID NO: 302	SEQ ID NO: 303
	AA	SGSSSNIGRNFVN	TNNQRPS	AAWDDSLNGWV
		SEQ ID NO: 304	SEQ ID NO: 305	SEQ ID NO: 306

26F12	NA	TCTGGAAGCCGCTCCA	ACTAATTATCAGCGGCCCTCA	GCAGTATGGGATGACAGCCT
27B3		ACATCGGAAGTAATTT		GAATGGTTGGGTG
		TGTAAAC
		SEQ ID NO: 307	SEQ ID NO: 308	SEQ ID NO: 309
	AA	SGSRSNIGSNFVN	TNYQRPS	AVWDDSLNGWV
		SEQ ID NO: 310	SEQ ID NO: 311	SEQ ID NO: 312

26D1	NA	TCTGGAAGCCGCTCCA	ACTAATAATCAGCGGCCCTCA	GCAGTATGGGATGACAGCCT
		ACATCGGAAGTAATTT		GAATGGTTGGGTG
		TGTAAAC
		SEQ ID NO: 313	SEQ ID NO: 314	SEQ ID NO: 315
	AA	SGSRSNIGSNFVN	TNNQRPS	AVWDDSLNGWV
		SEQ ID NO: 316	SEQ ID NO: 317	SEQ ID NO: 318

25G10	NA	AGGGCCAGTCAGAGTG	GGTGCATCCAGCAGGGCCACT	CAGCAGTATGGTAACTCACC
		TTAGCAGCAGCTACTT		GCTCACT
		AGCC
		SEQ ID NO: 319	SEQ ID NO: 320	SEQ ID NO: 321
	AA	RASQSVSSSYLA	GASSRAT	QQYGNSPLT
		SEQ ID NO: 322	SEQ ID NO: 323	SEQ ID NO: 324

23A10	NA	TCTGGAGATAGATTGG	CAAGATAATAAGTGGCCCTCA	CAGGCGTGGGACAGCAGcac
		GGGAGAAATATGTTTG		TGTGGTA
		C
		SEQ ID NO: 325	SEQ ID NO: 326	SEQ ID NO: 327
	AA	SGDRLGEKYVC	QDNKWPS	QAWDSSTVV
		SEQ ID NO: 328	SEQ ID NO: 329	SEQ ID NO: 330

19B5	NA	TCTGGAAGCAGGTCCA	ACTAATAATCAGCGGCCCTCA	GCAACATGGGATGACAGTAT
		ACATCGGAAGCAATTT		GAATGGTTGGGTG
		TGTAAAC
		SEQ ID NO: 331	SEQ ID NO: 332	SEQ ID NO: 333
	AA	SGSRSNIGSNFVN	TNNQRPS	ATWDDSMNGWV
		SEQ ID NO: 334	SEQ ID NO: 335	SEQ ID NO: 336

Anti-CDH19 Variable Region Amino Acid Sequences and Polynucleotide Sequences

TABLE IIa

Heavy Chain Variable Region Polynucleotide and Amino acid Sequences

SEQ
ID
NO.	DESIGNATION	SOURCE	TYPE	SEQUENCE

337	17H8	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
	23B6			CGGAGACCCTGTCCCTCACGTGCACTGTCTCTGGTGGCTCCAT
	28D10			CAATAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
				GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
				ACTACAACCCCTCCCTCAAGAGTCGCGTCACCATATCAGTAGA
				CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
				GCTGCGGACACGGCCCTGTATTACTGTGCGAGAGATTCCCGGT
				ATAGAAGTGGCTGGTACGATGCTTTTGATATCTGGGGCCAAGG
				GACAATGGTCACCGTCTCTTCA

338	17H8	artificial	aa	QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGK
	23B6			GLEWIGYIYYIGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
	28D10			AADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS

339	4A2	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
	5B4			CACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
	5C5			CAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCA
				GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGA
				GCGCCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATC
				AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
				GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
				GAAGCAGTGGCTGGTACTTCCAGTATTGGGGCCAGGGCACCCT
				GGTCACCGTCTCCTCA

340	4A2	artificial	aa	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHP
	5B4			GKGLEWIGYIYYTGSAYYNPSLKSRVTISVDTSKNQFSLKLSS
	5C5			VTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

341	16H2	artificial	nt	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
	20D3			GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
	23E7			CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
				GGGCTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCA
				CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
				GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
				TACAGCTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

342	16H2	artificial	aa	QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ
	20D3			GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
	23E7			RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

343	26F12	artificial	nt	CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
	27B3			GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTAGATACACCTT
				CACCAACTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
				GGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTGACT
				CAACCTACGCACAGAAGTTCCAGGGCAGACTCACCATGACCGG
				GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
				TACAACTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

344	26F12	artificial	aa	QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQ
	27B3			GLEWMGIINPSGGDSTYAQKFQGRLTMTGDTSTSTVYMELSSL
				RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

345	4B10	artificial	nt	CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
	4C2			GGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
				CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
				AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
				ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT
				CAGTGTCTCCTCA

346	4B10	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
	4C2			GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
				RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

347	4D3	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
	4F3			GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCTCCTT
				CAGTAGCTATGACATGGACTGGGTCCGCCAGACTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAGGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTTTCTGCAAATGAACAGCCTG
				AGAGTCGAGGACACGGCTGTGTATTACTGTGCGAGAGAAACTG
				GGGAGGGCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGT
				CACTGTCTCCTCA

348	4D3	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGK
	4F3			GLEWVAVIWYDGSNKYYADSVRGRFTISRDNSKNTLFLQMNSL
				RVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS

349	16E2	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
	17E10			GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCATCTT
	20B12			CAGTAGCTATGGCATGCACTGGGTCCGCCAGACTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTGATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACATTTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
				AGAGTCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGGT
				GGGAGCTGTCCTTTGACTACTGGGGCCAGGGAACCCTGGTCAC
				CGTCTCCTCA

350	16E2	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYGMHWVRQTPGK
	17E10			GLEWVAVIWYDGSNKYYADSVKGRFTISRDISKNTLYLQMNSL
	20B12			RVEDTAVYYCARDGWELSFDYWGQGTLVTVSS

351	1D10	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
	2C12			GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGTCAGTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGCGCGAGAAGGGCCG
				GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

352	1D10	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
	2C12			GLEWVSVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
				RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS

353	16C1	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
				CGGAGACCCTGTCCCTCACTTGTACTGTCTCTGGTGGCTCCAT
				CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
				GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
				ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAATAGA
				CACGTCCAAGAACCAGTTCTCCCTGACGCTGAGCTCTTTGACC
				GCTGCGGACACGGCCGTGTATTTCTGTGCGAGAGATGGGAGCA
				GTGGCTGGTACCGGTGGTTCGACCCCTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

354	16C1	artificial	aa	QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
				GLEWIGYIYYIGSTNYNPSLKSRVTMSIDTSKNQFSLTLSSLT
				AADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS

355	25G10	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
				CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
				CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
				GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
				ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGA
				CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
				GCTGCGGACACGGCCGTGTATTACTGTGCGAGAGATGGGAGCA
				GTGGCTGGTACCGGTGGTTCGACCCCTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

356	25G10	artificial	aa	QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
				GLEWIGYIYYIGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVT
				AADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS

357	16A4	artificial	nt	CAGGTGCAGCTGCAGGAGTCgGGCCCAGGACTGGCGAAgcctt
				cGGAGACcctgtccctcacctgCACTGTCTCTGGTGACTCCAT
				CACTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
				GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
				ATTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGA
				CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACC
				GCTGCGGACACGGCCGTGTATTACTGTGCGAGAGATCAAAGGC
				GGATAGCAGCAGCTGGTACCCACTTCTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

358	16A4	artificial	aa	QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGK
				GLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
				AADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSS

359	1F10	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
				CACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
				CAGCAGTGGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCA
				GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGA
				GCACCTACTACAACCCGTCCCTCACGAGTCGAGTTACCATATC
				AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
				GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
				GAAGCAGTGGCTGGTACTTCCAGCACTGGGGCCAGGGCACCCT
				GGTCACCGTCTCCTCA

360	1F10	artificial	aa	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHP
				GKGLEWIGYIYYSGSTYYNPSLTSRVTISVDTSKNQFSLKLSS
				VTAADTAVYYCARDGSSGWYFQHWGQGTLVTVSS

361	4A9	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
				CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
				CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
				GGACTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCA
				ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
				CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
				GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
				TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC
				CCA

362	4A9	artificial	aa	QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
				GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
				AADTAVYYCARNWAFHFDFWGQGTLVTVSS

363	4F7	artificial	nt	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
				CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
				CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
				GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
				ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
				CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
				GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
				TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC
				CTCA

364	4F7	artificial	aa	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK
				GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
				AADTAVYYCARNWAFHFDYWGQGTLVTVSS

365	22D1	artificial	nt	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
				GGGCCTCAGTGAGGGTTTCCTGCAAGGTTTCTGGATACACCTT
				CACCAGCTACTTTATTCACTGGGTACGCCAGGCCCCTGGACAA
				GGGCTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCA
				CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
				GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
				TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

366	22D1	artificial	aa	QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQ
				GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
				RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

367	19B5	artificial	nt	CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
				GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
				CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
				GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
				CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
				GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGcCTG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
				TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

368	19B5	artificial	aa	QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ
				GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
				RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

369	25F8	artificial	nt	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
				GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTT
				CACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAA
				GGACTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCA
				CAAGGTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
				GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCagcctG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAA
				TACAGCTATGGTTACATTttGACTACTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

370	25F8	artificial	aa	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ
				GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVFMELSSL
				RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

371	26D1	artificial	nt	CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
				GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTAGATACACCTT
				CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
				GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
				CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGG
				GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
				AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
				TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT
				GGTCACCGTCTCCTCA

372	26D1	artificial	aa	QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ
				GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
				RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

373	4D2	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
				CAGTAGTTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
				AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
				ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT
				CAGTGTCTCCTCA

374	4D2	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
				GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
				RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

375	4E10	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCACGAACACGCTGCATCTGCAAATGAACAGCCCG
				AGAGCCGAGGACACGGCTGTGTACTACTGTGCGAGAGAGTATA
				GGTACAGCTGGTACTTTGACTACTGGGGCCAGGGAACCCTGGT
				CACCGTCTCCTCA

376	4E10	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
				GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSTNTLHLQMNSP
				RAEDTAVYYCAREYRYSWYFDYWGQGTLVTVSS

377	22G10	artificial	nt	GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTG
				GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
				TAGCAGTTATGCCATGAACTGGGTCCGCCAGGCTCCAGGGAAG
				GGGCTGGAGTGGGTCTCAACTATTAGTGGTGGTGGTGCTAACA
				CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAG
				TGACAATTCCAAGAGCACGCTGTATCTGCAAATGAACAGCCTG
				AGAGCCGCGGACACGGCCGTATATCACTGTGCGAAAGGGGGAA
				TGGGGGGATACTACTACGGTATGGACGTCTGGGGCCAAGGGAC
				CACGGTCACCGTCTCCTCA

378	22G10	artificial	aa	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGK
				GLEWVSTISGGGANTYYADSVKGRFTISSDNSKSTLYLQMNSL
				RAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

379	2C12_LC#1	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGTCAGTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGCGCGAGAAGGGCCG
				GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

380	2C12_LC#1	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
				GLEWVSVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
				RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS

381	2H12_LC#2	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
				AATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
				GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

382	2H12_LC#2	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
				GLEWVAVIWYDGSNKYYTDSVKGRFTISRDNSKNTLYLQMNSL
				RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS

383	2G6_LC#1	artificial	nt	CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
				GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

384	2G6_LC#1	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
				GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
				RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

385	2H12	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
				AATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
				GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

386	2H12	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
				GLEWVAVIWYDGSNKYYTDSVKGRFTISRDNSKNTLYLQMNSL
				RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS

387	2G6	artificial	nt	CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
				AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
				GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

388	2G6	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
				GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
				RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

389	23A10	artificial	nt	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
				GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
				CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
				GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
				AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
				AGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTG
				AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
				GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
				GGGCCAAGGGACCACGGTCACCGTCTCCTCA

390	23A10	artificial	aa	QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK
				GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
				RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS

391	5E3	artificial	nt	GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCTG
				GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
				CAGTAGCTATAGCATGCACTGGGTCCGCCAGGCTCCAGGGAAG
				GGGCTGGAGTGGGTCTCATCCATTAGTAGTAGTAGTAGTTACA
				TATACTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAG
				AGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTG
				AGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGGGAAA
				CTGGAACTAACTACTACTACTACGGTATGGACGTCTGGGGCCA
				AGGGACCACGGTCACCGTCTCCTCA

392	5E3	artificial	aa	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMHWVRQAPGK
				GLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSL
				RAEDTAVYYCARGETGTNYYYYGMDVWGQGTTVTVSS

TABLE IIB

Light Chain Variable Region Polynucleotide and Amino acid Sequences

SEQ
ID
NO.	DESIGNATION	SOURCE	TYPE	SEQUENCE

393	17H8	artificial	nt	GACATTGTATTGACGCAGtctCCAGGCACCCTGTCTTTGTCTC
	23B6			CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
	28D10			TGCCGGCAGCTACCTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTCTGGTGCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATTACTGTCAGCAGTATGGTAAATCACCGATCACCTTCGGCC
				AAGGGACACGACTGGAGATGAAAGGA

394	17H8	artificial	aa	DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQ
	23B6			APRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
	28D10			YYCQQYGKSPITFGQGTRLEMKG

395	4A2	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
	5B4			CAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTCGGAATAT
	5C5			TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTACAGTG
				TATTACTGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTG
				GGACCAAAGTGGATATCAAACGA

396	4A2	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASRNISSSYLAWYQQKPGQ
	5B4			APRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFTV
	5C5			YYCQQYGSSFTFGPGTKVDIKR

397	16H2	artificial	nt	CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCG
	20D3			GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
	23E7			CGGAAGTAATTTTGTAAACTGGTACAAACAACTCCCAGGAACG
				GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
				TATTACTGTGCAACATGGGATGACAGCCTGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

398	16H2	artificial	aa	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT
	20D3			APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
	23E7			YYCATWDDSLNGWVFGGGTKLTVLG

399	26F12	artificial	nt	CAGTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCG
	27B3			GGCAGAAGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
				CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
				GCCCCCAAACTCCTCATCTATACTAATTATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
				TATTACTGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT


400	26F12	artificial	aa	QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGT
	27B3			APKLLIYTNYQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
				YYCAVWDDSLNGWVFGGGTKLTVLG

401	4B10	artificial	nt	GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
	4C2			CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
				TAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTG
				GCATCCCAGACAGATTCAGTGGCAGTGGGTCTGGGACAGACTT
				CGCTCTCACCATCAGCAGTCTGGAGCCTGAAGATTTTGCAGTG
				TATTACTGTCAGCAGTACAGTAACTCgtgGACGTTCGGCCAAG
				GGACCAAGGTGGAAATCAaacGA

402	4B10	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQ
	4C2			APRLLIYGASSRATGIPDRFSGSGSGTDFALTISSLEPEDFAV
				YYCQQYSNSWTFGQGTKVEIKR

403	4D3	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
	4F3			CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
				TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAACCTGAGGATTTTGCAGTG
				TATTACTGTCAGCAGTATGGTAGCTCGTGGACGTTCGGCCAAG
				GGACCAAGGTGGAAATCAAACGA

404	4D3	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
	4F3			APRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YYCQQYGSSWTFGQGTKVEIKR

405	16E2	artificial	nt	GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTG
	17E10			TAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGCAT
	20B12			TAGCAATTATTTAGCCTGGTTACAGCAGAAACCAGGGAAAGCC
				CCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGG
				TCCCATCAAAGTTCAGCGGCAGTGGATCTGGGACAGATTTCAC
				TCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTAT
				TACTGCCAACACTATTTTACTTACCCTCGGACGTTCGGCCAAG
				GGACCAAGGTGGAAATCAAACGA

406	16E2	artificial	aa	DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWLQQKPGKA
	17E10			PKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATY
	20B12			YCQHYFTYPRTFGQGTKVEIKR

407	1D10	artificial	nt	TCCTATGCGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
	2C12			GACAGACAGCCAGCCTCACCTGCTCTGGAGATAGATTGGGGGA
				AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
				TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
				CTGAGCGATTCTCTGGCTCCACCTCTGGTAACACAGCCACTCT
				GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
				TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA
				CCAAGCTGACCGTCCTAGGT

408	1D10	artificial	aa	SYALTQPPSVSVSPGQTASLTCSGDRLGEKYTCWYQQRPGQSP
	2C12			LLVIYQDTKRPSGIPERESGSTSGNTATLTISGTQAMDEADYY
				CQAWDSSTVVFGGGTKLTVLG

409	16C1	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGCCAGAGTGT
				TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCGGACTGGAGCCTGAAGATTTTGCAGTG
				TATCACTGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCG
				GAGGGACCAAGGTGGAGATCAAACGA

410	16C1	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
				APRLLIFGASSRATGIPDRFSGSGSGTDFTLTISGLEPEDFAV
				YHCQQYGNSPLTFGGGTKVEIKR

411	25G10	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
				TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGactT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATCACTGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCG
				GAGGGACCAAGGTGGAGATCAAACGA

412	25G10	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
				APRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YHCQQYGNSPLTFGGGTKVEIKR

413	16A4	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCtCTCCTGCAGGGCCAGTCAGAGTGT
				TAGCAGCAGTTATTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTACATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATTATTGTCAGCAGTACGGTAGCTCACCTTTCACTTTCGGCG
				GAGGGACCAAGGTGGAGATCAAACGA

414	16A4	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
				APRLLIYGTSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YYCQQYGSSPFTFGGGTKVEIKR

415	1F10	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCGGAGTAT
				TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATTACTGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTG
				GGACCAAAGTGGATATCAAACGA

416	1F10	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASRSISSSYLAWYQQKPGQ
				APRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YYCQQYGSSETFGPGTKVDIKR

417	4A9	artificial	nt	CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG
				GACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAACAT
				CGGGACAGGTTATGCTGTACACTGGTACCAGCAGTTTCCAGGA
				ACAGCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCT
				CAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
				AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
				GATTATTACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGG
				TGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

418	4A9	artificial	aa	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPG
				TAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
				DYYCQSYDSRLSGWVFGGGTKLTVLG

419	4F7	artificial	nt	CAGTCTGTgcTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG
				GGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAATAT
				CGGGACAGGTTATGATGTACACTGGTATCAGCAGcttcCAGGA
				ACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCT
				CAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
				AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
				GATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGG
				TGTTCGGCGGAGGGACCAGGTTGACCGTCCTAGGT

420	4F7	artificial	aa	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG
				TAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
				DYYCQSYDSSLSGWVFGGGTRLTVLG

421	22D1	artificial	nt	CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCG
				GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
				CGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACG
				GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
				TATTACTGTGCAACATGGGATGACAGTATGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

422	22D1	artificial	aa	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT
				APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
				YYCATWDDSMNGWVFGGGTKLTVLG

423	19B5	artificial	nt	CAGTCTGCGCTGACTCAGCCACCCTCAACGACTGGGACCCCCG
				GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGGTCCAACAT
				CGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACG
				GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
				TATTACTGCGCAACATGGGATGACAGTATGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAACTGACCGTCCTAGGT

424	19B5	artificial	aa	QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGT
				APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
				YYCATWDDSMNGWVFGGGTKLTVLG

425	25F8	artificial	nt	CAGTCTGCGCTGactCAGCCACCCTCAGCGACTGGGACCCCCG
				GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
				CGGAAGGAATTTTGTAAACTGGTATAAGCAGCTCCCAGGAACG
				GCCCCCAAAGTCCTCATTTATACTAATAATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
				TATTACTGTGCAGCATGGGATGACAGCCTGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

426	25F8	artificial	aa	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGT
				APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
				YYCAAWDDSLNGWVFGGGTKLTVLG

427	26D1	artificial	nt	CACTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCG
				GACAGAGGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
				CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
				GCCCCCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAG
				GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
				CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
				TATTACTGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGT
				TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

428	26D1	artificial	aa	HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT
				APKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
				YYCAVWDDSLNGWVFGGGTKLTVLG

429	4D2	artificial	nt	GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
				TAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCGCTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATTACTGTCAGCAGTATAGTAACTCGTGGACGTTCGGCCAAG
				GGACCAAGGTGGAAATCAAACGA

430	4D2	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQ
				APRLLIYGASSRAAGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YYCQQYSNSWTFGQGTKVEIKR

431	4E10	artificial	nt	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
				CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
				TGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
				GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGTCACTG
				GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGATTT
				CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
				TATTACTGTCAGCAATATAGTAACTCGTGGACGTTCGGCCAAG
				GGACCAAGGGGAAATCAAACGA

432	4E10	artificial	aa	EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQ
				APRLLIYGASSRVTGIPDRFSGSGSGTDFTLTISRLEPEDFAV
				YYCQQYSNSWTFGQGTKVEIKR

433	22G10	artificial	nt	GAAATAGTGATGACGCAGTCTCCAGTCACCCTGTCTCTGTCTC
				TAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTAT
				TAGCAGCAACTTAGCCTGGTTCCAGCAGAAACCTGGCCAGGCT
				CCCAGACTCCTCATCTATGGTGCATTTACCAGGGCCACTGGTA
				TCCCAGCCAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC
				TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTAT
				TACTGTCAGCAGTATAATTACTGGCCGCTCACTTTCGGCGGAG
				GGACCAAGGTGGAGATCAAGCGA

434	22G10	artificial	aa	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQA
				PRLLIYGAFTRATGIPARVSGSGSGTEFTLTISSLQSEDFAVY
				YCQQYNYWPLTFGGGTKVEIKR

435	2C12_LC#1	artificial	nt	GATGTTGTGATGactCAGtCTccActctccctgcCCGTCACCC
				TTGGACAGCCGGcctCCAtctcctgCAGGtCTAGTCAAAGcct
				cgtaTACAGTGATGGAAACAcctACTTGAATTGGTTTCAGCAG
				AGGCCAGGCCAATCTCCAAGGcgcctaATTTATAAGGTTTCTA
				ACTGGGactctGGGGtCCCAGACAGATTCAGCgGCAGTGGGTC
				AGGCActGATTTCACactGAAAAtCAGCAGGGTGGaggctgaG
				GATGTTGGGGTTTATTactgCATGCAAGGTATAGTGTGGCCGT
				GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAaCgA

436	2C12_LC#1	artificial	aa	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
				RPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAE
				DVGVYYCMQGIVWPCSFGQGTKLEIKR

437	2H12_LC#2	artificial	nt	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCC
				TTGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCT
				CGTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAG
				AGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTA
				ACTGGGACTCTGGGGTCCCAGACAGAATCAGCGGCAGTGGGTC
				AGGCACCGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAG
				GATGTTGGGGTTTATTACTGCATGCAAGATACACTGTGGCCGT
				GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA

438	2H12_LC#2	artificial	aa	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
				RPGQSPRRLIYKVSNWDSGVPDRISGSGSGTDFTLKISRVEAE
				DVGVYYCMQDTLWPCSFGQGTKLEIKR

439	2G6_LC#1	artificial	nt	GaTGTTGTGATGACTCagtctccACTCTCCCTGCCCGTCACCC
				ttggacaGCCGGCCTccaTCTCCTGCAGGTCTAGTCAAAGCCT
				CGTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAG
				AGGCCAGGCCAATCTCCACGGCGCCTAATTTATCAGGTTTCTA
				ACTGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC
				AGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAG
				GATGTTGGGATTTATTACTGCATGCAAGATACACTGTGGCCGT
				GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA

440	2G6_LC#1	artificial	aa	DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
				RPGQSPRRLIYQVSNWDSGVPDRFSGSGSGTDFTLKISRVEAE
				DVGIYYCMQDTLWPCSFGQGTKLEIKR

441	2H12	artificial	nt	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
				GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
				AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
				TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
				CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
				GACCATCAGCGGGACCCAGCCTATGGATGAGGCTGACTATTAC
				TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA
				CCAAGCTGACCGTCCtAGGT

442	2H12	artificial	aa	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP
				LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQPMDEADYY
				CQAWDSSTVVFGGGTKLTVLG

443	2G6	artificial	nt	TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
				GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
				AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
				TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
				CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
				GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
				TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA
				CCAAGCTGACCGTCCTAGGT

444	2G6	artificial	aa	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP
				LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
				CQAWDSSTVVFGGGTKLTVLG

445	23A10	artificial	nt	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
				GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
				GAAATATGTTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
				ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
				CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
				GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
				TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA
				CCAAGCTGACCGTCCTAGGT

446	23A10	artificial	aa	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVCWYQQKPGQSP
				ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
				CQAWDSSTVVFGGGTKLTVLG

447	5E3	artificial	nt	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
				GACAGACAGCCAGCATCACCTGCTCTGGAGATAAATTGGGGGA
				TGAATATGCTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
				GTGCTGGTCATCTATCAAGATAGCAAGCGGCCCTCAGGGATCC
				CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
				GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
				TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA
				CCAAGCTGACCGTCCTAGGT

448	5E3	artificial	aa	SYELTQPPSVSVSPGQTASITCSGDKLGDEYACWYQQKPGQSP
				VIVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
				CQAWDSSTVVFGGGTKLTVLG

TABLE IIc

Heavy Chain Variable Region Polynucleotide and Amino acid Sequences

13586 HC [hu anti-<huCDH19> 4F3 VH]

QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSICNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS

SEQ ID NO: 449

13589 HC [hu anti-<huCDH19> 4A9 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS

VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS

SEQ ID NO: 450

13590 HC [hu anti-<huCDH19> 4B10 VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR

FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

SEQ ID NO: 451

13874 HC [hu anti-<huCDH19> 17118.2 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS

SEQ ID NO: 452

13875 HC [hu anti-<huCDH19> 16C1.1 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 453

13876 HC [hu anti-<huCDH19> 16A4.1 VH]

QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSS

SEQ ID NO: 454

13877 HC [hu anti-<huCDH19> 22G10.1 VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 455

13878 HC [hu anti-<huCDH19> 20D3.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 456

13879 HC [hu anti-<huCDH19> 22D1.1 VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 457

13880 HC [hu anti-<huCDH19> 25F8.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 458

13881 HC [hu anti-<huCDH19> 26F12.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 459

13882 HC [hu anti-<huCDH19> 26D1.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 460

13883 HC [hu anti-<huCDH19> 25G10.1 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 461

13885 HC [hu anti-<huCDH19> 19B5.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 462

14022 HC [hu anti-<huCDH19> 4A2 VH]

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWICIYIYYTGSAYYNPSLKSRV

TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 463

14024 HC [hu anti-<huCDH19> 4A2 (1-472)(Q7E, H47P) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT

ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 464

14025 HC [hu anti-<huCDH19> 4A2 VH]

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV

TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 465

14026 HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, H47P) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT

ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 466

14027 HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT

ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 467

14028 HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E, W134Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT

ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYFQYWGQGTLVTVSS

SEQ ID NO: 468

14029 HC [hu anti-<huCDH19> 4A2 VH]

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV

TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS

SEQ ID NO: 469

14030 HC [hu anti-<huCDH19> 4F3 (1-471)(R17G) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS

SEQ ID NO: 470

14031 HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSICNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS

SEQ ID NO: 471

14032 HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A, R141Q) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSS

SEQ ID NO: 472

14033 HC [hu Anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E, D72E, R141Q)

VH]

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG

RFTISRDNSICNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSS

SEQ ID NO: 473

14034 HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E, D72E, W134Y,

R141Q) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGYYFDLWGQGTLVTVSS

SEQ ID NO: 474

14039 HC [hu anti-<huCDH19> 2G6 (1-477)(R17G, D61E, D72E, K94N) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 475

14040 HC [hu anti-<huCDH19> 16C1.1 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 476

14041 HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISCiYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 477

14042 HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K, D109E) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISCiYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLKLSSLTAADTAVYFCAREGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 478

14043 HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K, W132Y, W135Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISCiYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGYYRYFDPWGQGTLVTVSS

SEQ ID NO: 479

14044 HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISCiYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 480

14045 HC [hu anti-<huCDH19> 17118.2 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS

SEQ ID NO: 481

14046 HC [hu anti-<huCDH19> 17118.2 (1-471)(D109E) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSS

SEQ ID NO: 482

14047 HC [hu anti-<huCDH19> 17118.2 (1-471)(D109E, W132Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTALYYCARESRYRSGYYDAFDIWGQGTMVTVSS

SEQ ID NO: 483

14048 HC [hu anti-<huCDH19> 17118.2 (1-471)(D109E) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSS

SEQ ID NO: 484

14049 HC [hu anti-<huCDH19> 4F7 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL

DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS

SEQ ID NO: 485

14050 HC [hu anti-<huCDH19> 4F7 VVH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL

DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS

SEQ ID NO: 486

14051 HC [hu anti-<huCDH19> 4F7 (1-468)(W113Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL

DTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDYWGQGTLVTVSS

SEQ ID NO: 487

14052 HC [hu anti-<huCDH19> 4B10 (1-471)(R17G, D61E, D72E, W134Y) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR

FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDYSFDYWCiQGTLVSVSS

SEQ ID NO: 488

14053 HC [hu anti-<huCDH19> 4B10 VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR

FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

SEQ ID NO: 489

14054 HC [hu anti-<huCDH19> 4B10 (1-471)(R17G) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

SEQ ID NO: 490

14055 HC [hu anti-<huCDH19> 4B10 (1-471)(R17G, D61E, D72E) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR

FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS

SEQ ID NO: 491

14056 HC [hu anti-<huCDH19> 4A9 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS

VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS

SEQ ID NO: 492

14057 HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS

VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS

SEQ ID NO: 493

14058 HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS

VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS

SEQ ID NO: 494

14059 HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G, W113Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS

VDTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDFWGQGTLVTVSS

SEQ ID NO: 495

14060 HC [hu anti-<huCDH19> 20D3.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 496

14061 HC [hu anti-<huCDH19> 20D3.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 497

14062 HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 498

14063 HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 499

14064 HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 500

14065 HC [hu anti-<huCDH19> 22G10.1 (1-470)(S82R, A99E) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISRDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 501

14066 HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E, H105Y) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISSDNSKSTLYLQMNSLRAEDTAVYYCAKGGMGGYYYCiMDVWGQGTTVTVSS

SEQ ID NO: 502

14067 HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 503

14068 HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 504

14069 HC [hu anti-<huCDH19> 22G10.1 (1-470)(D72E, A99E) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSYAMNWVRQAPGKGLEWVSTISGGGANTYYAESVKGRF

TISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 505

14070 HC [hu anti-<huCDH19> 22G10.1 (1-470)(H105Y) VH]

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR

FTISSDNSKSTLYLQMNSLRAADTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 506

14071 HC [hu anti-<huCDH19> 16A4.1 (1-474)(T144L) VH]

QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV

DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTLVTVSS

SEQ ID NO: 507

14072 HC [hu anti-<huCDH19> 19B5.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 508

14073 HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS

SEQ ID NO: 509

14074 HC [hu anti-<huCDH19> 19B5.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 510

14075 HC [hu anti-<huCDH19> 19B5.1 VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELS SLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 511

14076 HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELS SLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS

SEQ ID NO: 512

14077 HC [hu anti-<huCDH19> 23A10.3 (1-474)(L92Q) VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR

FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 513

14078 HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G, L92Q) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG

RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 514

14079 HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G, D61E, D72E,

L92Q) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYEGSNKYYAESVKGR

FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 515

14080 HC [hu anti-<huCDH19> 23A10.3 VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR

FTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 516

14081 HC [hu anti-<huCDH19> 25G10.1 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS

SEQ ID NO: 517

14082 HC [hu anti-<huCDH19> 25G10.1 (1-469)(D109E, W132Y, W135Y) VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS

VDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYRYFDPWGQGTLVTVSS

SEQ ID NO: 518

14083 HC [hu anti-<huCDH19> 26D1.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 519

14084 HC [hu anti-<huCDH19> 26D1.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 520

14085 HC [hu anti-<huCDH19> 26D1.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 521

14086 HC [hu anti-<huCDH19> 26D1.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 522

14087 HC [hu anti-<huCDH19> 26D1.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLYLHFDYWGQGTLVTVSS

SEQ ID NO: 523

14088 HC [hu anti-<huCDH19> 26D1.1 (1-469)(R27G, G82R) VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR

VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS

SEQ ID NO: 524

14089 HC [hu anti-<huCDH19> 26F12.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 525

14090 HC [hu anti-<huCDH19> 26F12.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 526

14091 HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 527

14092 HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 528

14093 HC [hu anti-<huCDH19> 25F8.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 529

14094 HC [hu anti-<huCDH19> 25F8.1 VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 530

14095 HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 531

14096 HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS

SEQ ID NO: 532

14097 HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y, W133Y) VH]

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR

VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS

SEQ ID NO: 533

14098 HC [hu anti-<huCDH19> 22D1.1 VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 534

14099 HC [hu anti-<huCDH19> 22D1.1 VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 535

14100 HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS

SEQ ID NO: 536

14101 HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS

SEQ ID NO: 537

14102 HC [hu anti-<huCDH19> 22D1.1 (1-469)(F90Y) VH]

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV

TMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS

SEQ ID NO: 538

13591 HC [hu anti-<huCDH19> 4F7 VH]

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKOLEWIGYIYYSGSTNYNPSLKSRVTISL

DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS

SEQ ID NO: 539

14301 HC [hu anti-<huCDH19> 2G6 VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 540

14302 HC [hu anti-<huCDH19> 2G6 (1-477)(R17G, K94N) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 541

14303 HC [hu anti-<huCDH19> 2G6 (1-477)(D61E, D72E) VH]

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 542

14304 HC [hu anti-<huCDH19> 2G6 (1-477)(R17G) VH]

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS

SEQ ID NO: 543

TABLE IId

Light Chain Variable Region Amino acid Sequences

13586 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 544

13589 LC [hu anti-<huCDH19> 4A9 VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPGTAPKLLIYGNNNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG

SEQ ID NO: 545

13590 LC [hu anti-<huCDH19> 4B10 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR

SEQ ID NO: 546

13874 LC [hu anti-<huCDH19> 17H8.2 VL]

DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT

DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKG

SEQ ID NO: 547

13875 LC [hu anti-<huCDH19> 16C1.1 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 548

13876 LC [hu anti-<huCDH19> 16A4.1 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKVEIKR

SEQ ID NO: 549

13877 LC [hu anti-<huCDH19> 22G10.1 VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF

TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 552

13878 LC [hu anti-<huCDH19> 20D3.1 VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDESDYYCATWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 554

13879 LC [hu anti-<huCDH19> 22D1.1 VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 555

13880 LC [hu anti-<huCDH19> 25F8.1 VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 556

13881 LC [hu anti-<huCDH19> 26F12.1 VL]

QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 557

13882 LC [hu anti-<huCDH19> 26D1.1 VL]

HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 555

13883 LC [hu anti-<huCDH19> 25G10.1 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 556

13885 LC [hu anti-<huCDH19> 19B5.1 VL]

QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 557

14022 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKR

SEQ ID NO: 558

14024 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q,T102A,P141Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR

SEQ ID NO: 559

14025 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q, T102A) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKR

SEQ ID NO: 560

14026 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q, T102A) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKR

SEQ ID NO: 561

14027 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q, T102A, P141Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR

SEQ ID NO: 562

14028 LC [hu anti-<huCDH19> 4A2 (1-236)(N30Q, T102A, P141Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR

SEQ ID NO: 563

14029 LC [hu anti-<huCDH19> 4A2 (1-236)(R29Q, N30S) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF

TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKR

SEQ ID NO: 564

14030 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 565

14031 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 566

14032 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 567

14033 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 568

14034 LC [hu anti-<huCDH19> 4F3 VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR

SEQ ID NO: 569

14039 LC [hu anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT

LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG

SEQ ID NO: 570

14040 LC [hu anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 571

14041 LC [hu anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 572

14042 LC [hu anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 573

14043 LC [hu anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 574

14044 LC [hu anti-<huCDH19> 16C1.1 (1-235)(G95R, H105Y, G141Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGNSPLTFGQGTKVEIKR

SEQ ID NO: 575

14045 LC [hu anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]

DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT

DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR

SEQ ID NO: 576

14046 LC [hu anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]

DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT

DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR

SEQ ID NO: 577

14047 LC [hu anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]

DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT

DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR

SEQ ID NO: 578

14048 LC [hu anti-<huCDH19> 17H8.2 (1-235)(S57Y, G149R) VL]

DIVLTQSPOTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT

DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR

SEQ ID NO: 579

14049 LC [hu anti-<huCDH19> 4F7 (1-239)(H57Y) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLG

SEQ ID NO: 580

14050 LC [hu anti-<huCDH19> 4F7 (1-239)(H57Y, D110E) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLG

SEQ ID NO: 581

14051 LC [hu anti-<huCDH19> 4F7 (1-239)(D110E) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLG

SEQ ID NO: 582

14052 LC [hu anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]

EIVLTQSPOTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR

SEQ ID NO: 583

14053 LC [hu anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]

EIVLTQSPOTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR

SEQ ID NO: 584

14054 LC [hu anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]

EIVLTQSPOTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR

SEQ ID NO: 585

14055 LC [hu anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]

EIVLTQSPOTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD

FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR

SEQ ID NO: 586

14056 LC [hu anti-<huCDH19> 4A9 (1-239)(F47L) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG

SEQ ID NO: 587

14057 LC [hu anti-<huCDH19> 4A9 (1-239)(F47L) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG

SEQ ID NO: 588

14058 LC [hu anti-<huCDH19> 4A9 (1-239)(F47L, D110E) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLG

SEQ ID NO: 589

14059 LC [hu anti-<huCDH19> 4A9 (1-239)(F47L, D110E) VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLG

SEQ ID NO: 590

14060 LC [hu anti-<huCDH19> 20D3.1 (1-235)(S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 591

14061 LC [hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 592

14062 LC [hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 593

14063 LC [hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A, D111E, N135Q) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDESLQGWVFGGGTKLTVLG

SEQ ID NO: 594

14064 LC [hu anti-<huCDH19> 20D3.1 (1-235)(W109Y) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDESDYYCATYDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 595

14065 LC [hu anti-<huCDH19> 22G10.1 VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF

TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 596

14066 LC [hu anti-<huCDH19> 22G10.1 VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF

TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 597

14067 LC [hu anti-<huCDH19> 22G10.1 (1-234)(Q97E, S98P) VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF

TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 598

14068 LC [hu anti-<huCDH19> 22G10.1 (1-234)(V78F, Q97E, S98P) VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSOSGSGTEF

TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 599

14069 LC [hu anti-<huCDH19> 22G10.1 (1-234)(V78F, Q97E, S98P) VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTEF

TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 600

14070 LC [hu anti-<huCDH19> 22G10.1 VL]

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF

TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR

SEQ ID NO: 601

14071 LC [hu anti-<huCDH19> 16A4.1 (1-235)(G141Q) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGSSPFTFGQGTKVEIKR

SEQ ID NO: 602

14072 LC [hu anti-<huCDH19> 19B5.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 603

14073 LC [hu anti-<huCDH19> 19B5.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 604

14074 LC [hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A) VL]

QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 605

14075 LC [hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A, D111E,

N135Q) VL]

QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLG

SEQ ID NO: 606

14076 LC [hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A, W109Y,

D111E, N135Q) VL]

QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLG

SEQ ID NO: 607

14077 LC [hu anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA

TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG

SEQ ID NO: 608

14078 LC [hu anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA

TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG

SEQ ID NO: 609

14079 LC [hu anti-<huCDH19> 23A10.3 (1-231)(C42S, D110E) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA

TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG

SEQ ID NO: 610

14080 LC [hu anti-<huCDH19> 23A10.3 (1-231)(C42Y) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVYWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA

TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG

SEQ ID NO: 611

14081 LC [hu anti-<huCDH19> 25G10.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 612

14082 LC [hu anti-<huCDH19> 25G10.1 (1-235)(H105Y) VL]

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD

FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR

SEQ ID NO: 613

14083 LC [hu anti-<huCDH19> 26D1.1 (1-235)(S7P) VL]

HSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 614

14084 LC [hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P) VL]

QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 615

14085 LC [hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y) VL]

QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVYDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 616

14086 LC [hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y, D111E, N135Q) VL]

QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG

SEQ ID NO: 617

14087 LC [hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y, D111E, N135Q) VL]

QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG

SEQ ID NO: 618

14088 LC [hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P) VL]

QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 619

14089 LC [hu anti-<huCDH19> 26F12.1 (1-235)(S7P) VL]

QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 620

14090 LC [hu anti-<huCDH19> 26F12.1 (1-235)(S7P, D111E) VL]

QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLG

SEQ ID NO: 621

14091 LC [hu anti-<huCDH19> 26F12.1 (1-235)(S7P, D111E) VL]

QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLG

SEQ ID NO: 622

14092 LC [hu anti-<huCDH19> 26F12.1 (1-235)(S7P, W109Y, D111E, N135Q) VL]

QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG

SEQ ID NO: 623

14093 LC [hu anti-<huCDH19> 25F8.1 (1-235)(K45Q) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 624

14094 LC [hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 625

14095 LC [hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLG

SEQ ID NO: 626

14096 LC [hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A, D111E) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCAAWDESLNGWVFGGGTKLTVLG

SEQ ID NO: 627

14097 LC [hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A, D111E, N135Q) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT

SASLAISGLQSEDEADYYCAAWDESLQGWVFGGGTKLTVLG

SEQ ID NO: 628

14098 LC [hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 629

14099 LC [hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, D111E, N135Q) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLG

SEQ ID NO: 630

14100 LC [hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, W109Y, D111E,

N135Q) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLG

SEQ ID NO: 631

14101 LC [hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, W109Y) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATYDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 632

14102 LC [hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A) VL]

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS

ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG

SEQ ID NO: 633

13591 LC [hu anti-<huCDH19> 4F7 VL]

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG

TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLG

SEQ ID NO: 634

14301 LC [hu anti-<huCDH19> 2G6 (1-234)(D110E) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT

LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG

SEQ ID NO: 635

14302 LC [hu anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT

LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG

SEQ ID NO: 636

14303 LC [hu anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT

LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG

SEQ ID NO: 637

14304 LC [hu anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA

TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG

SEQ ID NO: 638

Anti-CDH19 Variable and Constant Region Polynucleotide and Amino Acid Sequences

TABLE IIIa

Heavy Chain Variable and Contant
Region Polynucleotide and Amino acid Sequences

2G6

SEQ ID NO: 639

CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT

GCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG

CTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGAC

CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCT

GAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCGGTATAATAGGAACTATAGGCTACTACTAC

GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCG

GTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCAC

ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC

AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC

AAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTC

CTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC

CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC

GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG

GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA

GAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC

TGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTC

ACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTG

CACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 640

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

4A2

SEQ ID NO: 641

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGC

ACTGTCTCTGGTGGCTCCATCAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCAGGG

AAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGAGCGCCTACTACAACCCGTCCCTCAAG

AGTCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACT

CCCGCGGACACGGCCGTGTATTACTCTGCGAGAGATGGAAGCAGTGGCTGGTACTTCCAGTATTGG

GGCCAGGGCACCCTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATCCTCCGTGATCCATGAGGCTCTCCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 642

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

4A9

SEQ ID NO: 643

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC

ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAGGGA

CTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA

GTCACCTTATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG

GACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCTTCCACTTTGACTTCTGGGGCCAGGGAACC

CTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG

AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACG

GTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA

GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC

TGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC

AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

CCCCCAAAACCCAAGGACACCCTCATTATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTCGAC

GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG

CACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCC

ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCA

TCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC

GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG

CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG

GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTC

TCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 644

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

4B10

SEQ ID NO: 645

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT

GCAGCCTCTGGATTCACCTTCAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG

CTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATGAATACTATGCAGACTCCGTGAAGGGC

CGATTCACCATCTCCAGAGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTGAGAGCT

GAGGACACGGCTGTATATTACTGTGCGAGAGAACGATATTTTGACTGGTCTTTTGACTACTGGGGC

CAGGGAACCCTGGTCAGCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC

TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA

CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA

CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG

ACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAA

TCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTC

TTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG

GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG

CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTC

ACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC

CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC

CTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC

TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG

CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGG

TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG

AAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 646

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

4F3

SEQ ID NO: 647

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT

GCAGCGTCTGGATTCTCCTTCAGTAGCTATGACATGTACTCGGTCCGCCAGACTCCAGGCAAGGGG

CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAGGGGC

CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTTTCTGCAAATGAACAGCCTGAGAGTC

GAGGACACGGCTGTGTATTACTGTGCGAGAGAAACTGGGGAGGGCTGGTACTTCGATCTCTGGGGC

CGTGGCACCCTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC

TCCTCCAAGAGCACCTCTGCGGGCACAGCGGCCCTGGGCTCCCTGCTCAAGGACTACTTCCCCGAA

CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA

CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG

ACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAA

TCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTC

TTCCTCTTCCCCCCAAAACCCAAGTACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG

GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG

CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTC

ACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC

CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC

CTCCCCCCATCCCCGTAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC

TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACG

CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGG

TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG

AAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 648

QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

4F7

SEQ ID NO: 649

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC

ACTGTCTCTGGTGGCTCCATCAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA

CTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA

GTCACCATATCATTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG

GACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCTTCCACTTTGACTACTGGGGCCAGGGAACC

CTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG

AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACG

GTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA

GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC

TGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC

AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC

CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC

GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG

CACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCC

ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCA

TCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC

GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG

CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG

GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTC

TCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 650

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISLDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

16A4

SEQ ID NO: 651

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGCGAAGCCTTCGGAGACCCTGTCCCTCACCTGC

ACTGTCTCTGGTGACTCCATCACTAGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGA

CTGGAGTGGATTGGGTATATCTATTACAGCGGGAGCACCAATTACAACCCCTCCCTCAAGAGTCGA

GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCG

GACACGGCCGTGTATTACTGTGCGAGAGATCAAAGGCGGATAGCAGCAGCTGGTACCCACTTCTAC

GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACTGTCTCCTCAGCTTCCACCAAGGGCCCATCC

GTCTTCCCCCTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGCCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCAC

ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC

AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC

AAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTC

CTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC

CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC

GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG

GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA

GAACCACAGGTCTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC

TGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTC

ACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTG

CACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 652

QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

16C1

SEQ ID NO: 653

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACTTGT

ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA

CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA

GTCACCATGTCAATAGACACGTCCAAGAACCAGTTCTCCCTGACGCTGAGCTCTTTGACCGCTGCG

GACACGGCCGTGTATTTCTGTGCGAGAGATGGGAGCAGTGGCTGGTACCGGTGGTTCGACCCCTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 654

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

17H8

SEQ ID NO: 655

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACGTGC

ACTGTCTCTGGTGGCTCCATCAATAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA

CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGC

GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG

GACACGGCCCTGTATTACTGTGCGAGAGATTCCCGGTATAGAAGTGGCTGGTACGATGCTTTTGAT

ATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCC

CTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTAC

TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCG

GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTG

GGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTT

GAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGA

CCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTC

ACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGC

GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC

AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAAC

AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG

GTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC

AAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC

AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC

AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC

TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 656

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

19B5

SEQ ID NO: 657

CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC

AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAAGGG

CTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC

AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATCT

GAGGACACGGCCGTCTATTACTCTGCGCGAGGGGGGATACAGCTATGGTTACATTTGGACTACTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 658

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

20D3

SEQ ID NO: 659

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC

AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAAGGG

CTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC

AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATCT

GAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGATACAGCTATGGTTACATTTTGACTACTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 660

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

22D1

SEQ ID NO: 661

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAGGGTTTCCTGC

AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTACGCCAGGCCCCTGGACAAGGG

CTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC

AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATCT

GAGGACACGGCCGTCTATTACTCTGCGCGACTGGGGGATACAGCTATGGTTACATTTTGACTACTG

GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC

GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC

CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC

CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCC

CAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC

AGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG

CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGT

CCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGC

CCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA

CACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGG

CTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGAC

CACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAG

CAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC

GCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 662

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDCTVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

22G10

SEQ ID NO: 663

GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT

GCAGCCTCTGGATTCACCTTTAGCAGTTATGCCATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGG

CTGGAGTGGGTCTCAACTATTAGTGGTGGTGGTGCTAACACATACTACGCAGACTCCGTGAAGGGC

CGGTTCACCATCTCCAGTGACAATTCCAAGAGCACGCTGTATCTGCAAATGAACAGCCTGAGAGCC

GCGGACACGGCCGTATATCACTGTGCGAAAGGGGGAATGGGGGGATACTACTACGGTATGGACGTC

TGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTG

GCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTC

CCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT

GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGC

ACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG

CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCG

TCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACA

TGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG

GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC

GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA

GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG

TACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAA

GGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG

ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAG

AGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC

ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 664

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

23A10

SEQ ID NO: 665

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT

GCAGCGTCTGGATTCACCTTCAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAGGGG

CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGC

CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTGAGAGCC

GAGGACTCGGCTGTGTATTACTGTCCGAGAAGGGCCGCTATACCTCGAACTACGGGCTACTACTAT

GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCC

GTCTTCCCCCTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCAC

ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC

AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC

AAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTC

CTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC

CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC

GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG

GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA

GAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC

TGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTC

ACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTG

CACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 666

QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG

RFTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

25F8

SEQ ID NO: 667

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC

AAGGCATCTGGATACACCTTCACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAAGGA

CTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCACAAGGTACGCACAGAAGTTCCAGGGC

AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATCT

GAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAATACAGCTATGGTTACATTTTGACTACTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATCGGCAGCCCGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 668

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

25G10

SEQ ID NO: 669

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC

ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA

CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA

GTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG

GACACGCCCGTGTATTACTGTGCGAGAGATGGGAGCAGTGGCTGGTACCGGTGGTTCGACCCCTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 670

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

26D1

SEQ ID NO: 671

CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGT

AAGGCATCTAGATACACCTTCACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAAGGG

CTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACACAACCTACGCACAGAAGTTCCAGGGC

AGAGTCACCATGACCGGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCT

GAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGATAAAACTATGGTTACATTTTGACTATTGG

GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC

CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC

CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC

AAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG

GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC

CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC

ACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC

AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 672

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

26F12

SEQ ID NO: 673

CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC

AAGGCATCTAGATACACCTTCACCAACTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAAGGG

CTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTGACTCAACCTACGCACAGAAGTTCCAGGGC

AGACTCACCATGACCGGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCT

GAGGACACCTGCCGTCTATTACTCTGCGAGAGGTTGGATACAACTATGGTTACATTTTGACTACTG

GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC

GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC

CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC

CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCC

CAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC

AGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG

CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGT

CCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGC

CCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA

CACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGG

CTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGAC

CACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAG

CAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC

GCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

SEQ ID NO: 674

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

TABLE IIIb

Light Chain Variable and Contant
Region Polynucleotide and Amino acid Sequences

2G6

SEQ ID NO: 675

TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGC

TCTGGAGATAGGTTGGGGGAAAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTG

CTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCT

GGTAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAG

GCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTCAGCCCAAG

GCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCCAACAAGGCCACACTA

GTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCC

GTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGGCCAGCAGC

TACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCATGAA

GGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 676

SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNS

GNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATL

VCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHE

GSTVEKTVAPTECS

4A2

SEQ ID NO: 677

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCGGAATATTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTACAGTGTATTAC

TGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGTACGGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC

CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC

AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 678

EIVLTQSPGTLSLSPGERATLSCRASRNISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGS

GSGTDFTLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASV

VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGEC

4A9

SEQ ID NO: 679

CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAGGACAGAGGGTCACCATCTCCTGC

ACTGGGAGCAGCTCCAACATCGGGACAGGTTATGCTGTACACTGGTACCAGCAGTTTCCAGGAACA

GCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCTCAGGGGTTCCTGACCGATTCTCTGGC

TCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTAT

TACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTC

CTAGGTCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCC

AACAAGGCCACACTAGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAG

GCAGATGGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAG

TACGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGC

CAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 680

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPGTAPKLLIYGNNNRPSGVPDRFSG

SKSGTSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQA

NKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSC

QVTHEGSTVEKTVAPTECS

4B10

SEQ ID NO: 681

GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTGTTAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAGGCT

CCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGATTCAGTGGCAGT

GGGTCTGGGACAGACTTCGCTCTCACCATCAGCAGTCTGGAGCCTGAAGATTTTGCAGTGTATTAC

TGTCAGCAGTACAGTAACTCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC

CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC

AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 682

EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQAPRLLIYGASSRATGIPDRFSGS

GSGTDFALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV

VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGEC

4F3

SEQ ID NO: 683

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAACCTGAGGATTTTGCAGTGTATTAC

TGTCAGCAGTATGGTAGCTCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGTACGGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT

GTGTGCCTCCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTCGAAGGTGGATAACGCCCTC

CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC

AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 684

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS

GSGTDFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV

VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGEC

4F7

SEQ ID NO: 685

CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAGGGCAGAGGGTCACCATCTCCTGC

ACTGGGAGCAGCTCCAATATCGGGACAGGTTATGATGTACACTGGTATCAGCAGCTTCCAGGAACA

GCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGC

TCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTAT

TACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGGTGTTCGGCGGAGGGACCAGGTTGACCGTC

CTAGGTCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCC

AACAAGGCCACACTAGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAG

GCAGATGGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAG

TACGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGC

CAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 686

QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSG

SKSGTSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQA

NKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSC

QVTHEGSTVEKTVAPTECS

16A4

SEQ ID NO: 687

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTGTTAGCAGCAGTTATTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTATGGTACATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTAT

TGTCAGCAGTACGGTAGCTCACCTTTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACT

GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCT

GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC

CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC

AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC

CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 688

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGS

GSGTDFTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS

VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

16C1

SEQ ID NO: 689

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCATCCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCGGACTGGAGCCTGAAGATTTTGCAGTGTATCAC

TGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACT

GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCT

GTTGTGTGCCTCCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTCGAAGGTGGATAACGCC

CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC

AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC

CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTCTTGA

SEQ ID NO: 690

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGS

GSGTDFTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS

VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

17H8

SEQ ID NO: 691

GACATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTGTTGCCGGCAGCTACCTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTCTCGTCCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTAC

TGTCAGCAGTATGGTAAATCACCGATCACCTTCGGCCAAGGGACACGACTGGAGATGAAAGGAACT

GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCT

GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC

CTCCAATCGGGTAACTCCCAGGAGAGTCTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC

AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC

CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 692

DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGS

GSGTDFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKGTVAAPSVFIFPPSDEQLKSGTAS

VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

19B5

SEQ ID NO: 693

CAGTCTGCGCTGACTCAGCCACCCTCAACGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT

TCTGGAAGCAGGTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACGGCC

CCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTAC

TGCGCAACATGGGATGACAGTATGAATGGTTGGGTGTTCGGCGGAGGGACCAAACTGACCGTCCTA

GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 694

QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGS

KSGTSASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

20D3

SEQ ID NO: 695

CAGTCTCCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT

TCTGGAAGCAGCTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACGGCC

CCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTAC

TGTGCAACATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA

GGTCAGCCCAAGGCTTCCCCCTCGCTCACTCTCTTCCCACCCTCCTCTGAGGAGCTTCAATCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 696

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGS

KSGTSASLAISGLQSEDESDYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

22D1

SEQ ID NO: 697

CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT

TCTGGAAGCAGCTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACCGCC

CCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTAC

TGTGCAACATGGGATGACAGTATGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA

GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 698

QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGS

KSGTSASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

22G10

SEQ ID NO: 699

GAAATAGTGATGACGCAGTCTCCAGTCACCCTGTCTCTGTCTCTAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTATTAGCAGCAACTTAGCCTGGTTCCAGCAGAAACCTGGCCAGGCTCCC

AGACTCCTCATCTATGGTGCATTTACCAGGGCCACTGGTATCCCAGCCAGGGTCAGTGGCAGTGGG

TCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGT

CAGCAGTATAATTACTGGCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAGCGAACTGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC

CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC

AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA

SEQ ID NO: 700

EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSG

SGTEFTLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV

VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGEC

23A10

SEQ ID NO: 701

TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGC

TCTGGAGATAGATTGGGGGAGAAATATGTTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATA

CTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCT

GGGAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAG

GCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGACCGTCCTAGGTCAGCCCAAG

GCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACTG

GTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCC

GTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGC

TATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCATGAA

GGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 702

SYELTQPPSVSVSPGQTASITCSGDRLGEKYVCWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNS

GNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATL

VCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHE

GSTVEKTVAPTECS

25F8

SEQ ID NO: 703

CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT

TCTGGAAGCAGCTCCAACATCGGAAGGAATTTTGTAAACTGGTATAAGCAGCTCCCAGGAACGGCC

CCCAAAGTCCTCATTTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTAC

TGTGCAGCATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA

GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 704

QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGS

KSGTSASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

25G10

SEQ ID NO: 705

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCC

TGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT

CCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT

GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATCAC

TGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACT

GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCT

GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC

CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC

AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC

CATCAGGCTCCTGAGCTCGCCCGTCACAAACTAGCTTCAACAGGGCTAGAGTCTTCTA

SEQ ID NO: 706

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGS

GSGTDFTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS

VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

26D1

SEQ ID NO: 707

CACTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCGGACAGAGGGTCACCATCTCTTGT

TCTGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCC

CCCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTAC

TGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA

GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGCCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 708

HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGS

KSGTSASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

26F12

SEQ ID NO: 709

CAGTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCGGGCAGAAGGTCACCATCTCTTGT

TCTGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCC

CCCAAACTCCTCATCTATACTAATTATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC

AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTAC

TGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA

GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC

AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA

GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC

GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG

GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA

SEQ ID NO: 710

QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGS

KSGTSASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN

KATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

TABLE 111c

Heavy Chain Variable and Contant
Region Polynucleotide and Amino acid Sequences

13586_HC [hu anti-<huCDH19> 4F3 VH]::huIgG1z

SEQ ID NO: 711

QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13589_HC [hu anti-<huCDH19> 4A9 VH]::huIgG1z

SEQ ID NO: 712

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13590_HC [hu anti-<huCDH19> 4B10 VH]::huIgG1z

SEQ ID NO: 713

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13874_HC [hu anti-<huCDH19> 17H8.2 VH]::huIgG1z

SEQ ID NO: 714

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13875_HC [hu anti-<huCDH19> 16C1.1 VH]::huIgG1z

SEQ ID NO: 715

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13876_HC [hu anti-<huCDH19> 16A4.1 VH]::huIgG1z

SEQ ID NO: 716

QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQCINVFSCSVMHEALHNHYTQKSLSLSPGK

13877_HC [hu anti-<huCDH19> 22G10.1 VH]::huIgG1z

SEQ ID NO: 717

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13878_HC [hu anti-<huCDH19> 20D3.1 VH]::huIgG1z

SEQ ID NO: 718

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13879_HC [hu anti-<huCDH19> 22D1.1 VH]::huIgG1z

SEQ ID NO: 719

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13880_HC [hu anti-huCDH19> 25F8.1 VH]::huIgG1z

SEQ ID NO: 720

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13881_HC [hu anti-<huCDH19> 26F12.1 VH]::huIgG1z

SEQ ID NO: 721

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13882_HC [hu anti-<huCDH19> 26D1.1 VH]::huIgG1z

SEQ ID NO: 722

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13883_HC [hu anti-<huCDH19> 25G10.1 VH]::huIgG1z

SEQ ID NO: 723

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13885_HC [hu anti-<huCDH19> 19B5.1 VH]::huIgG1z

SEQ ID NO: 724

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARCiGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14022_HC [hu anti-<huCDH19> 4A2 VH]::huIgG1z

SEQ ID NO: 725

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14024_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E,H47P) VH]::huIgG1z

SEQ ID NO: 726

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14025_HC [hu anti-<huCDH19> 4A2 VH]::huIgG1z

SEQ ID NO: 727

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14026_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E,H47P) VH]::huIgG1z

SEQ ID NO: 728

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14027_HC [hu anti-<huCDH19> 4A2 (1-472)

(Q17E,H47P,D111E) VH]::huIgG1z

SEQ ID NO: 729

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14028_HC [hu anti-<huCDH19> 4A2 (1-472)

(Q17E,H47P,D111E,W134Y) VH]::huIgG1z

SEQ ID NO: 730

QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14029_HC [hu anti-<huCDH19> 4A2 VH]::huIgG1z

SEQ ID NO: 731

QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLK

SRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14030_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G) VH]::huIgG1z

SEQ ID NO: 732

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14031_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G,T47A) VH]::huIgG1z

SEQ ID NO: 733

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14032_HC [hu anti-<huCDH19> 4F3 (1-471)

(R17G,T47A,R141Q) VH]::huIgG1z

SEQ ID NO: 734

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14033_HC [hu anti-<huCDH19> 4F3 (1-471)

(R17G,T47A,D61E,D72E,R141Q) VH]::huIgG1z

SEQ ID NO: 735

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14034_HC [hu anti-<huCDH19> 4F3 (1-471)

(R17G,T47A,D61E,D72E,W134Y,R141Q) VH]::huIgG1z

SEQ ID NO: 736

QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG

RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGYYFDLWGQGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14039_HC [hu anti-<huCDH19> 2G6 (1-477)

(R17G,D61E,D72E,K94N) VH]::huIgG1z

SEQ ID NO: 737

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14040_HC [hu anti-<huCDH19> 16C1.1 VH]::huIgG1z

SEQ ID NO: 738

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14041_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]::huIgG1z

SEQ ID NO: 739

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14042_HC [hu anti-<huCDH19> 16C1.1 (1-469)

(T92K,D109E) VH]::huIgG1z

SEQ ID NO: 740

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLKLSSLTAADTAVYFCAREGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14043_HC [hu anti-<huCDH19> 16C1.1 (1-469)

(T92K,W132Y,W135Y) VH]::huIgG1z

SEQ ID NO: 741

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLKLSSLTAADTAVYFCARDGSSGYYRYFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14044_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]::huIgG1z

SEQ ID NO: 742

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSIDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14045_HC [hu anti-<huCDH19> 17H8.2 VH]::huIgG1z

SEQ ID NO: 743

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14046_HC [hu anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]::huIgG1z

SEQ ID NO: 744

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14047_HC [hu anti-<huCDH19> 17H8.2 (1-471)

(D109E,W132Y) VH]::huIgG1z

SEQ ID NO: 745

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARESRYRSGYYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14048_HC [hu anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]::huIgG1z

SEQ ID NO: 746

QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFP

LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14049_HC [hu anti-<huCDH19> 4F7 VH]::huIgG1z

SEQ ID NO: 747

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISLDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14050_HC [hu anti-<huCDH19> 4F7 VH]::huIgG1z

SEQ ID NO: 748

QVQLQESGPGLVKPSETESLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISLDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14051_HC [hu anti-<huCDH19> 4F7 (1-468)(W113Y) VH]::huIgG1z

SEQ ID NO: 749

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISLDTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14052_HC [hu anti-<huCDH19> 4B10 (1-471)

(R17G,D61E,D72E,W134Y) VH]::huIgG1z

SEQ ID NO: 750

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDYSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14053_HC [hu anti-<huCDH19> 4B10 VH]::huIgG1z

SEQ ID NO: 751

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14054_HC [hu anti-<huCDH19> 4B10 (1-471)(R17G) VH]::huIgG1z

SEQ ID NO: 752

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14055_HC [hu anti-<huCDH19> 4B10 (1-471)

(R17G,D61E,D72E) VH]::huIgG1z

SEQ ID NO: 753

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKG

RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14056_HC [hu anti-<huCDH19> 4A9 VH]::huIgG1z

SEQ ID NO: 754

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14057_HC [hu anti-<huCDH19> 4A9 (1-468)(F55I,A56G) VH]::huIgG1z

SEQ ID NO: 755

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14058_HC [hu anti-<huCDH19> 4A9 (1-468)(F55I,A56G) VH]::huIgG1z

SEQ ID NO: 756

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14059_HC [hu anti-<huCDH19> 4A9 (1-468)

(F55I,A56G,W113Y) VH]::huIgG1z

SEQ ID NO: 757

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSR

VTLSVDTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14060_HC [hu anti-<huCDH19> 20D3.1 VH]::huIgG1z

SEQ ID NO: 758

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14061_HC [hu anti-<huCDH19> 20D3.1 VH]::huIgG1z

SEQ ID NO: 759

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14062_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 760

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSERSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14063_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 761

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14064_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 762

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14065_HC [hu anti-<huCDH19> 22G10.1 (1-470)

(S82R,A99E) VH]::huIgG1z

SEQ ID NO: 763

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISRDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14066_HC [hu anti-<huCDH19> 22G10.1 (1-470)

(A99E,H105Y) VH]::huIgG1z

SEQ ID NO: 764

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAEDTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14067_HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]::huIgG1z

SEQ ID NO: 765

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14068_HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]::huIgG1z

SEQ ID NO: 766

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14069_HC [hu anti-<huCDH19> 22G10.1 (1-470)

(D72E,A99E) VH]::huIgG1z

SEQ ID NO: 767

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYAESVKG

RFTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14070_HC [hu anti-<huCDH19> 22G10.1 (1-470)(H105Y) VH]::huIgG1z

SEQ ID NO: 768

EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKG

RFTISSDNSKSTLYLQMNSLRAADTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPL

APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14071_HC [hu anti-<huCDH19> 16A4.1 (1-474)(T144L) VH]::huIgG1z

SEQ ID NO: 769

QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTLVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14072_HC [hu anti-<huCDH19> 19B5.1 VH]::huIgG1z

SEQ ID NO: 770

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14073_HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 771

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14074_HC [hu anti-<huCDH19> 19B5.1 VH]::huIgG1z

SEQ ID NO: 772

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14075_HC [hu anti-<huCDH19> 19B5.1 VH]::huIgG1z

SEQ ID NO: 773

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIMPISVSTSYAQKFQGR

VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAP

SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14076_HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 774

QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14077_HC [hu anti-<huCDH19> 23A10.3 (1-474)(L92Q) VH]::huIgG1z

SEQ ID NO: 775

QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG

RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14078_HC [hu anti-<huCDH19> 23A10.3 (1-474)

(R17G,L92Q) VH]::huIgG1z

SEQ ID NO: 776

QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG

RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14079_HC [hu anti-<huCDH19> 23A10.3 (1-474)

(R17G,D61E,D72E,L92Q) VH]::huIgG1z

SEQ ID NO: 777

QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYEGSNKYYAESVKG

RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14080_HC [hu anti-<huCDH19> 23A10.3 VH]::huIgG1z

SEQ ID NO: 778

QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG

RFTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14081_HC [hu anti-<huCDH19> 25G10.1 VH]::huIgG1z

SEQ ID NO: 779

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14082_HC [hu anti-<huCDH19> 25G10.1 (1-469)

(D109E,W132Y,W135Y) VH]::huIgG1z

SEQ ID NO: 780

QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSR

VTMSVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYRYFDPWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14083_HC [hu anti-<huCDH19> 26D1.1 VH]::huIgG1z

SEQ ID NO: 781

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14084_HC [hu anti-<huCDH19> 26D1.1 VH]::huIgG1z

SEQ ID NO: 782

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14085_HC [hu anti-<huCDH19> 26D1.1 VH]::huIgG1z

SEQ ID NO: 783

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14086_HC [hu anti-<huCDH19> 26D1.1 VH]::huIgG1z

SEQ ID NO: 784

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14087_HC [hu anti-<huCDH19> 26D1.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 785

QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14088_HC [hu anti-<huCDH19> 26D1.1 (1-469)

(R27G,G82R) VH]::huIgG1z

SEQ ID NO: 786

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQG

RVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14089_HC [hu anti-<huCDH19> 26F12.1 VH]::huIgG1z

SEQ ID NO: 787

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14090_HC [hu anti-<huCDH19> 26F12.1 VH]::huIgG1z

SEQ ID NO: 788

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14091_HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 789

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14092_HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 790

QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG

RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14093_HC [hu anti-<huCDH19> 25F8.1 VH]::huIgG1z

SEQ ID NO: 791

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGI1NPSGGSTRYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14094_HC [hu anti-<huCDH19> 25F8.1 VH]::huIgG1z

SEQ ID NO: 792

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14095_HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]::huIgG1z

SEQ ID NO: 793

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14096_HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]::huIgG1z

SEQ ID NO: 794

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14097_HC [hu anti-<huCDH19> 25F8.1 (1-469)

(F90Y,W133Y) VH]::huIgG1z

SEQ ID NO: 795

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQG

RVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14098_HC [hu anti-<huCDH19> 22D1.1 VH]::huIgG1z

SEQ ID NO: 796

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14099_HC [hu anti-<huCDH19> 22D1.1 VH]::huIgG1z

SEQ ID NO: 797

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14100_HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 798

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14101_HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]::huIgG1z

SEQ ID NO: 799

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14102_HC [hu anti-<huCDH19> 22D1.1 (1-469)(F90Y) VH]::huIgG1z

SEQ ID NO: 800

QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQG

RVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLA

PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

13591_HC [hu anti-<huCDH19> 4F7 VH]::huIgG1z

SEQ ID NO: 801

QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR

VTISLDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14301_HC [hu anti-<huCDH19> 2G6 VH]::huIgG1z

SEQ ID NO: 802

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14302_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G,K94N) VH]::huIgG1z

SEQ ID NO: 803

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14303_HC [hu anti-<huCDH19> 2G6 (1-477)(D61E,D72E) VH]::huIgG1z

SEQ ID NO: 804

QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

14304_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G) VH]::huIgG1z

SEQ ID NO: 805

QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD

RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPS

VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

TABLE IIId

Light Chain Variable and Contant Region
Polynucleotide and Amino
acid Sequences

	13586 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 806

	13589 LC [hu anti-<huCDH19> 4A9
	VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAV
	HWYQQFPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGG
	TKLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 807

	13590 LC [hu anti-<huCDH19> 4B10
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLA
	WYHQRPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 808

	13874 LC [hu anti-<huCDH19> 17118.2
	VL]::huKLC
	DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
	WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRL
	EMKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 809

	13875 LC [hu anti-<huCDH19> 16C1.1
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC

	SEQ ID NO: 810
	13876 LC [hu anti-<huCDH19> 16A4.1
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 811

	13877 LC [hu anti-<huCDH19> 22G10.1
	VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTE
	FTLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 812

	13878 LC [hu anti-<huCDH19> 20D3.1
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCATWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 813

	13879 LC [hu anti-<huCDH19> 22D1.1
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCATWDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 814

	13880 LC [hu anti-<huCDH19> 25F8.1
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 815

	13881 LC [hu anti-<huCDH19> 26F12.1
	VL]::huLLC-C2
	QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 816

	13882 LC [hu anti-<huCDH19> 26D1.1
	VL]::huLLC-C2
	HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 817

	13883 LC [hu anti-<huCDH19> 25G10.1
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 818

	13885 LC [hu anti-<huCDH19> 19B5.1
	VL]::huLLC-C2
	QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCATWDDSMNGWVFGGGT
	ICLTVLGQPICAAPSVTLFPPSSEELQANKATLVC
	LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSN
	NKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
	TVAPTECS
	SEQ ID NO: 819

	14022 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWY
	QQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDFTL
	TISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKRT
	VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
	KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
	TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
	SEQ ID NO: 820

	14024 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q, T102A, P141Q)
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLA
	WYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVD
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSICADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 821

	14025 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q, T102A) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLA
	WYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVD
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 822

	14026 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q, T102A) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLA
	WYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVD
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 823

	14027 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q, T102A, P141Q) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLA
	WYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVD
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 824

	14028 LC [hu anti-<huCDH19> 4A2
	(1-236)(N30Q, T102A, P141Q) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAW
	YQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTD
	FTLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDI
	KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
	REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
	STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
	GEC
	SEQ ID NO: 825

	14029 LC [hu anti-<huCDH19> 4A2
	(1-236)(R290, N30S) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSISSSYLA
	WYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVD
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSONSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 826

	14030 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKEKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 827

	14031 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQICPGQAPRLLIYGASSRATGIPDRFSGSGSG
	TDFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 828

	14032 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEI
	KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
	REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
	STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
	GEC
	SEQ ID NO: 829

	14033 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWY
	QQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTL
	TISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRT
	VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
	KVQWKVDNALQSONSQESVTEQDSKDSTYSLSSTL
	TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
	SEQ ID NO: 830

	14034 LC [hu anti-<huCDH19> 4F3
	VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 831

	14039 LC [hu anti-<huCDH19> 2G6
	(1-234)(C42S, D110E) VL]::huLLC-C1
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWY
	QQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTV
	LGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 832

	14040 LC [hu anti-<huCDH19> 16C1.1
	(1-235)(H105Y) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 833

	14041 LC [hu anti-<huCDH19> 16C1.1
	(1-235)(H105Y) VL]::hul(LC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 834

	14042 LC [hu anti-<huCDH19> 16C1.1
	(1-235)(H105Y) VL]::hul(LC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 835

	14043 LC [hu anti-<huCDH19> 16C1.1
	(1-235)(H105Y) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 836

	14044 LC [hu anti-<huCDH19> 16C1.1
	(1-235)(G95R, H105Y, G141Q)
	VL]::hul(LC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGNSPLTFGQGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 837

	14045 LC [hu anti-<huCDH19> 17H8.2
	(1-235)(G149R) VL]::huKLC
	DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
	WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRL
	EMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 838

	14046 LC [hu anti-<huCDH19> 17H8.2
	(1-235)(G149R) VL]::huKLC
	DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
	WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRL
	EMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 839

	14047 LC [hu anti-<huCDH19> 17118.2
	(1-235)(G149R) VL]::huKLC
	DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
	WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRL
	EMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 840

	14048 LC [hu anti-<huCDH19> 17118.2
	(1-235)(S57Y, G149R) VL]::huKLC
	DIVLTQSPOTLSLSPGERATLSCRASQSVAGSYLA
	WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRL
	EMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 841

	14049 LC [hu anti-<huCDH19> 4F7
	(1-239)(H57Y) VL]::huLLC-C2
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDV
	HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGG
	TRLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 842

	14050 LC [hu anti-<huCDH19> 4F7
	(1-239)(1157Y, D110E) VL]::huLLC-C2
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDV
	HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGG
	TRLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 843

	14051 LC [hu anti-<huCDH19> 4F7
	(1-239)(D110E) VL]::huLLC-C2
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDV
	HWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGG
	TRLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 844

	14052 LC [hu anti-<huCDH19> 4B10
	(1-236)(H45Q, A90T) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLA
	WYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 845

	14053 LC [hu anti-<huCDH19> 4B10
	(1-236)(11450, A90T) VL]::huKLC
	EIVLTQSPOTLSLSPGERATLSCRASQSVSNTYLA
	WYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 846

	14054 LC [hu anti-<huCDH19> 4B10
	(1-236)(11450, A90T) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLA
	WYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 847

	14055 LC [hu anti-<huCDH19> 4B10
	(1-236)(H45Q, A90T) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLA
	WYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGT
	DFTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 848

	14056 LC [hu anti-<huCDH19> 4A9
	(1-239)(F47L) VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAV
	HWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGG
	TKLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 849

	14057 LC [hu anti-<huCDH19> 4A9
	(1-239)(F47L) VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAV
	HWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGG
	TKLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADOSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 850

	14058 LC [hu anti-<huCDH19> 4A9
	(1-239)(F47L, D110E) VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAV
	HWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYESRLSGWVEGGG
	TKLTVLGQPKANPTVTLEPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 851

	14059 LC [hu anti-<huCDH19> 4A9
	(1-239)(F47L, D110E) VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAV
	HWYQQLPGTAPKWYGNNNRPSGVPDRFSGSKSGTS
	ASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTK
	LTVLGQPKANPTVTLFPPSSEELQANKATLVCLIS
	DFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKY
	AASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
	PTECS
	SEQ ID NO: 852

	14060 LC [hu anti-<huCDH19> 20D3.1
	(1-235)(S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 853

	14061 LC [hu anti-<huCDH19> 20D3.1
	(1-235)(K45Q, S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSLNGWVFGGGT
	KLTVLGQPICAAPSVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 854

	14062 LC [hu anti-<huCDH19> 20D3.1
	(1-235)(K45Q, S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSLNGWVEGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 855

	14063 LC [hu anti-<huCDH19> 20D3.1
	(1-235)(K45Q, S102A, D111E, N135Q)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDESLQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 856

	14064 LC [hu anti-<huCDH19> 20D3.1
	(1-235)(W109Y) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCATYDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 857

	14065 LC [hu anti-<huCDH19> 22G10.1
	VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTE
	FTLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 858

	14066 LC [hu anti-<huCDH19> 22G10.1
	VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTE
	FTLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 859

	14067 LC [hu anti-<huCDH19> 22G10.1
	(1-234)(097E, S981P) VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTE
	FTLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 860

	14068 LC [hu anti-<huCDH19> 22G10.1
	(1-234)(V78F, 097E, S98P) VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTE
	FTLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNEY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 861

	14069 LC [hu anti-<huCDH19> 22G10.1
	(1-234)(V78F, 097E, S98P) VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTE
	FTLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 862

	14070 LC [hu anti-<huCDH19> 22G10.1
	VL]::huKLC
	EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAW
	FQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTE
	FTLTISSLQSEDFAVYYCQQYNYWPLTEGGOTKVE
	IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNEY
	PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
	SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
	RGEC
	SEQ ID NO: 863

	14071 LC [hu anti-<huCDH19> 16A4.1
	(1-235)(G141Q) VL]::huKLC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGSSPFTFGQGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 864

	14072 LC [hu anti-<huCDH19> 19B5.1
	(1-235)(K45Q, S102A) VL]::huLLC-C2
	QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 865

	14073 LC [hu anti-<huCDH19> 19B5.1
	(1-235)(K450, S102A) VL]::huLLC-C2
	QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNEVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 866

	14074 LC [hu anti-<huCDH19> 19B5.1
	(1-235)(T11V, K450, S102A)
	VL]::huLLC-C2
	QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSMNGWVFGGOT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 867

	14075 LC [hu anti-<huCDH19> 19B5.1
	(1-235)(T11V, K45Q, S102A, D111E,
	N135Q) VL]::huLLC-C2
	QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDESMQGWVEGGGT
	KLTVLGQPKAAPSVTLEPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 868

	14076 LC [hu anti-<huCDH19> 19B5.1
	(1-235)(T11V, K45Q, S102A, W109Y,
	D111E, N135Q) VL]::huLLC-C2
	QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATYDESMQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 869

	14077 LC [hu anti-<huCDH19> 23A10.3
	(1-231)(C42S) VL]::huLLC-C2
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWY
	QQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTV
	LGQPKAAPSVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 870

	14078 LC [hu anti-<huCDH19> 23A10.3
	(1-231)(C42S) VL]::huLLC-C2
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWY
	QQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTV
	LGQPKAAPSVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 871

	14079 LC [hu anti-<huCDH19> 23A10.3
	(1-231)(C42S, D110E) VL]::huLLC-C2
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWY
	QQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTV
	LGQPKAAPSVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 872

	14080 LC [hu anti-<huCDH19> 23A10.3
	(1-231)(C42Y) VL]::huLLC-C2
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVYWY
	QQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWDSSTVVFOGGTKLTV
	LGQPKAAPSVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 873

	14081 LC [hu anti-<huCDH19> 25G10.1
	(1-235)(H105Y) VL]::hul(LC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 874

	14082 LC [hu anti-<huCDH19> 25G10.1
	(1-235)(H105Y) VL]::hul(LC
	EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA
	WYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGT
	DFTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKV
	EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
	YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
	LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
	NRGEC
	SEQ ID NO: 875

	14083 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(S7P) VL]::huLLC-C2
	HSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 876

	14084 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(H1Q, S7P) VL]::huLLC-C2
	QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 877

	14085 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(H1Q, S7P, W109Y)
	VL]::huLLC-C2
	QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVYDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 878

	14086 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(H1Q, S7P, W109Y, D111E,
	N135Q) VL]::huLLC-C2
	QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVYDESLQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 879

	14087 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(H1Q, S7P, W109Y, D111E, N1350)
	VL]::huLLC-C2
	QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVYDESLQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 880

	14088 LC [hu anti-<huCDH19> 26D1.1
	(1-235)(H1Q, S7P) VL]::huLLC-C2
	QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 881

	14089 LC [hu anti-<huCDH19> 26E12.1
	(1-235)(S7P) VL]::huLLC-C2
	QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 882

	14090 LC [hu anti-<huCDH19> 26F12.1
	(1-235)(S7P, D111E) VL]::huLLC-C2
	QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDESLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 883

	14091 LC [hu anti-<huCDH19> 26E12.1
	(1-235)(S7P, D111E) VL]::huLLC-C2
	QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVWDESLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 884

	14092 LC [hu anti-<huCDH19> 26E12.1
	(1-235)(S7P, W109Y, D111E, N1350)
	VL]::huLLC-C2
	QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVN
	WYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAVYDESLQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 885

	14093 LC [hu anti-<huCDH19> 25E8.1
	(1-235)(K45Q) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 886

	14094 LC [hu anti-<huCDH19> 25E8.1
	(1-235)(K45Q, S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 887

	14095 LC [hu anti-<huCDH19> 25F8.1
	(1-235)(K450, S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 888

	14096 LC [hu anti-<huCDH19> 25E8.1
	(1-235)(K450, S102A, D111E)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAAWDESLNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 889

	14097 LC [hu anti-<huCDH19> 25E8.1
	(1-235)(K45Q, S102A, D111E, N135Q)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCAAWDESLQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 890

	14098 LC [hu anti-<huCDH19> 22D1.1
	(1-235)(K450, S102A)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 891

	14099 LC [hu anti-<huCDH19> 22D1.1
	(1-235)(K45Q, S102A, D111E, N135Q)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDESMQGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 892

	14100 LC [hu anti-<huCDH19> 22D1.1
	(1-235)(K45Q, S102A, W109Y, D111E,
	N1350) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATYDESMQGWVFOGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 893

	14101 LC [hu anti-<huCDH19> 22D1.1
	(1-235)(K450, S102A, W109Y)
	VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATYDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 894

	14102 LC [hu anti-<huCDH19> 22D1.1
	(1-235)(K45Q, S102A) VL]::huLLC-C2
	QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVN
	WYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
	SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGT
	KLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
	SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNK
	YAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
	APTECS
	SEQ ID NO: 895

	13591 LC [hu anti-<huCDH19> 4F7
	VL]::huLLC-C1
	QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDV
	HWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
	TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGG
	TRLTVLGQPKANPTVTLFPPSSEELQANKATLVCL
	ISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNN
	KYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT
	VAPTECS
	SEQ ID NO: 896

	14301 LC [hu anti-<huCDH19> 2G6
	(1-234)(D110E) VL]::huLLC-C1
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWY
	QQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTV
	LGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPIE
	CS
	SEQ ID NO: 897

	14302 LC [hu anti-<huCDH19> 2G6
	(1-234)(C42S, D110E) VL]::huLLC-C1
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWY
	QQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTV
	LGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPIE
	CS
	SEQ ID NO: 898

	14303 LC [hu anti-<huCDH19> 2G6
	(1-234)(C42S, D110E)
	VL]::huLLC-C1
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWY
	QQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTV
	LGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPIE
	CS
	SEQ ID NO: 899

	14304 LC [hu anti-<huCDH19> 23A10.3
	(1-231)(C42S) VL]::huLLC-C2
	SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWY
	QQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
	TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTV
	LGQPKAAPSVTLFPPSSEELQANKATLVCLISDFY
	PGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
	SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTE
	CS
	SEQ ID NO: 900

TABLE Iva

HEAVY CHAIN CDRs

Ab	Type	CDR 1	CDR 2	CDR 3

14039	AA	SYGMH	FIWYE	RAGIIGT
14303		SEQ ID	GSNKY	IGYYYGM
		NO: 28	YAESV	DV
			KD	SEQ ID
			SEQ ID	NO: 30
			NO: 901

14027	AA	SSGYY	YIYYT	EGSSGW
		WS	GSAYY	YFQY
		SEQ ID	NPSLK	SEQ ID
		NO: 46	S	NO: 902
			SEQ ID
			NO: 47

14028	AA	SSGYY	YIYYT	EGSSGY
		WS	GSAYY	YFQY
		SEQ ID	NPSLK	SEQ ID
		NO: 46	S	NO: 903
			SEQ ID
			NO: 47

14059	AA	GYYWS	YFSYS	NYAFHF
		SEQ ID	GSTNY	DF
		NO: 52	NPSLK	SEQ ID
			S	NO: 904
			SEQ ID
			NO: 53

14052	AA	SYDMH	VISYE	ERYFD
		SEQ ID	GTNEY	YSFDY
		NO: 58	YAESV	SEQ ID
			KG	NO: 906
			SEQ ID
			NO: 905

14055	AA	SYDMH	VISYE	ERYFDW
		SEQ ID	GTNEY	SFDY
		NO: 58	YAESV	SEQ ID
			KG	NO: 60
			SEQ ID
			NO: 905

14033	AA	SYDMD	VIWYE	ETGEGW
		SEQ ID	GSNKY	YFDL
		NO: 70	YAESV	SEQ ID
			RG	NO: 72
			SEQ ID
			NO: 907

14034	AA	SYDMD	VIWYE	ETGEGY
		SEQ ID	GSNKY	YFDL
		NO: 70	YAESV	SEQ ID
			RG	NO: 908
			SEQ ID
			NO: 907

14051	AA	SYSWS	YIYYS	NYAFH
		SEQ ID	GSTNY	FDY
		NO: 82	NPSLK	SEQ ID
			S	NO: 909
			SEQ ID
			NO: 83

14046	AA	SYYWS	YIYYI	ESRYRS
14048		SEQ ID	GSTNY	GWYDAF
		NO: 94	NPSLK	DI
			S	SEQ ID
			SEQ ID	NO: 910
			NO: 95

14047	AA	SYYWS	YIYYI	ESRYRS
		SEQ ID	GSTNY	GYYDAF
		NO: 94	NPSLK	DI
			S	SEQ ID
			SEQ ID	NO: 911
			NO: 95

14042	AA	GYYWS	YIYYI	EGSSGW
		SEQ ID	GSTNY	YRWFDP
		NO: 100	NPSLK	SEQ ID
			S	NO: 912
			SEQ ID
			NO: 101

14043	AA	GYYWS	YIYYI	DGSSGY
		SEQ ID	GSTNY	YRYFDP
		NO: 100	NPSLK	SEQ ID
			S	NO: 913
			SEQ ID
			NO: 101

14069	AA	SYAMN	TISGG	GGMGGY
		SEQ ID	GANTY	YYGMDV
		NO: 118	YAESV	SEQ ID
			KG	NO: 120
			SEQ ID
			NO: 914

14062	AA	SYFIH	IINPI	GGIQLY
14063		SEQ ID	SVSTS	LHFDY
14064		NO: 124	YAQKF	SEQ ID
			QG	NO: 915
			SEQ ID
			NO: 125

14100	AA	SYFIH	IINPI	GGIQLY
14101		SEQ ID	SVSTS	LHLDY
		NO: 130	YAQKF	SEQ ID
			QG	NO: 916
			SEQ ID
			NO: 131

14097	AA	SYYIH	IINPS	GGIQLY
		SEQ ID	GGSTR	LHFDY
		NO: 136	YAQKF	SEQ ID
			QG	NO: 917
			SEQ ID
			NO: 137

14091	AA	NYYMS	IINPS	GGIQL
14092		SEQ ID	GGDST	YLHFDY
		NO: 142	YAQKF	SEQ ID
			QG	NO: 918
			SEQ ID
			NO: 143

14087	AA	SYYMS	IIHPS	GGIKLY
		SEQ ID	GGDTT	LHFDY
		NO: 148	YAQKF	SEQ ID
			QG	NO: 919
			SEQ ID
			NO: 149

14082	AA	GYYWS	YIYYI	EGSSGY
		SEQ ID	GSTNY	YRYFDP
		NO: 154	NPSLK
			S
			SEQ ID
			NO: 155	SEQ ID
				NO: 920

14079	AA	RYGIH	VIWYE	RAGIPGT
		SEQ ID	GSNKY	TGYYYGM
		NO: 160	YAESV	DV
			KG	SEQ ID
			SEQ ID	NO: 162
			NO: 921

14073	AA	SYFIH	IINPI	GGIQLY
14076		SEQ ID	SVSTS	LHLDY
		NO: 1	YAQKF	SEQ ID
			QG	NO: 3
			SEQ ID
			NO: 2
	AA	SYGMH	VIWYD	RAGIIG
		SEQ ID	GSNKY	TTGYYY
		NO: 4	YADSV	GMDV
			KG	SEQ ID
			SEQ ID	NO: 6
			NO: 5

TABLE IVb

LIGHT CHAIN CDRs

Ab	Type	CDR 1	CDR 2	CDR 3

14039	AA	SGDRL	QDTKR	QAWES
14302		GEKYT	PS	STW
14303		S	SEQ ID	SEQ ID
		SEQ ID	NO: 197	NO: 923
		NO: 922

14301	AA	SGDRL	QDTKR	QAWES
		GEKYT	PS	STW
		C	SEQ ID	SEQ ID
		SEQ ID	NO: 197	NO: 923
		NO: 196

14022	AA	RASRQ	GPSSR	QQYGS
14024		ISSSY	AT	SFT
14025		LA	SEQ ID	SEQ ID
14026		SEQ ID	NO: 215	NO: 216
14027		NO: 924
14028

14029	AA	RASQS	GPSSR	QQYGS
		ISSSY	AT	SFT
		LA	SEQ ID	SEQ ID
		SEQ ID	NO: 215	NO: 216
		NO: 925

14058	AA	TGSSS	GNNNR	QSYES
14059		NIGTG	PS	RLSGW
		YAVH	SEQ ID	V
		SEQ ID	NO: 221	SEQ ID
		NO: 220		NO: 926

14050	AA	TGSSS	GNSNR	QSYES
14051		NIGTG	PS	SLSGW
		YDVH	SEQ ID	V
		SEQ ID	NO: 251	SEQ ID
		NO: 250		NO: 927

14063	AA	SGSSS	TNNQR	ATWDE
		NIGSN	PS	SLQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 293	SEQ ID
		NO: 292		NO: 928

14064	AA	SGSSS	TNNQR	ATYDD
		NIGSN	PS	SLNGW
		FVN	SEQ ID	V
		SEQ ID	NO: 293	SEQ ID
		NO: 292		NO: 929

14099	AA	SGSSS	TNNQR	ATWDE
		NIGSN	PS	SMQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 299	SEQ ID
		NO: 298		NO: 930

14100	AA	SGSSS	TNNQR	ATYDE
		NIGSN	PS	SMQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 299	SEQ ID
		NO: 298		NO: 931

14101	AA	SGSSS	TNNQR	ATYDD
		NIGSN	PS	SMNGW
		FVN	SEQ ID	V
		SEQ ID	NO: 299	SEQ ID
		NO: 298		NO: 932

14096	AA	SGSSS	TNNQR	AAWDE
		NIGRN	PS	SLNGW
		FVN	SEQ ID	V
		SEQ ID	NO: 305	SEQ ID
		NO: 304		NO: 933

14097	AA	SGSSS	TNNQR	AAWDE
		NIGRN	PS	SLQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 305	SEQ ID
		NO: 304		NO: 934

14090	AA	SGSRS	TNYQR	AVWDE
14091		NIGSN	PS	SLNGW
		FVN	SEQ ID	V
		SEQ ID	NO: 311	SEQ ID
		NO: 310		NO: 935

14092	AA	SGSRS	TNYQR	AVYDE
		NIGSN	PS	SLQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 311	SEQ ID
		NO: 310		NO: 936

14085	AA	SGSRS	TNNQR	AVYDD
		NIGSN	PS	SLNGW
		FVN	SEQ ID	V
		SEQ ID	NO: 317	SEQ ID
		NO: 316		NO: 937

14086	AA	SGSRS	TNNQR	AVYDE
14087		NIGSN	PS	SLQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 317	SEQ ID
		NO: 316		NO: 938

14077	AA	SGDRL	QDNKW	QAWDS
14078		GEKYV	PS	STW
14304		S	SEQ ID	SEQ ID
		SEQ ID	NO: 329	NO: 330
		NO: 939

14079	AA	SGDRL	QDNKW	QAWES
		GEKYV	PS	STW
		S	SEQ ID	SEQ ID
		SEQ ID	NO: 329	NO: 940
		NO: 939

14080	AA	SGDRL	QDNKW	QAWDS
		GEKYV	PS	STW
		Y	SEQ ID	SEQ ID
		SEQ ID	NO: 329	NO: 330
		NO: 941

14075	AA	SGSRS	TNNQR	ATWDE
		NIGSN	PS	SMQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 335	SEQ ID
		NO: 334		NO: 942

14076	AA	SGSRS	TNNQR	ATYDE
		NIGSN	PS	SMQGW
		FVN	SEQ ID	V
		SEQ ID	NO: 335	SEQ ID
		NO: 334		NO: 943

Human and Cynomologous Monkey Cadherin-19 Sequences

TABLE V

SEQ
ID	DESIG-
NO.	NATION	SOURCE	TYPE	SEQUENCE

944	Human	Human	aa	MNCYLLLRFMLGIPLLWPCL
	Cadherin-			GATENSQTKKVKQPVRSHLR
	19			VKRGWVWNQFFVPEEMNTTS
				HHIGQLRSDLDNGNNSFQYK
				LLGAGAGSTFIIDERTGDIY
				AIQKLDREERSLYILRAQVI
				DIATGRAVEPESEFVIKVSD
				INDNEPKFLDEPYEAIVPEM
				SPEGTLVIQVTASDADDPSS
				GNNARLLYSLLQGQPYFSVE
				PTTGVIRISSKMDRELQDEY
				WVIIQAKDMIGQPGALSGTT
				SVLIKLSDVNDNKPIFKESL
				YRLTVSESAPTGTSIGTIMA
				YDNDIGENAEMDYSIEEDDS
				QTFDIITNHETQEGIVILKK
				KVDFEHQNHYGIRAKVKNHH
				VPEQLMKYHTEASTTFIKIQ
				VEDVDEPPLFLLPYYVFEVF
				EETPQGSFVGVVSATDPDNR
				KSPIRYSITRSKVFNINDNG
				TITTSNSLDREISAWYNLSI
				TATEKYNIEQISSIPLYVQV
				LNINDHAPEFSQYYETYVCE
				NAGSGQVIQTISAVDRDESI
				EEHHFYFNLSVEDTNNSSFT
				IIDNQDNTAVILTNRTGFNL
				QEEPVFYISILIADNGIPSL
				TSTNTLTIHVCDCGDSGSTQ
				TCQYQELVLSMGFKTEVIIA
				ILICIMIIFGFIFLTLGLKQ
				RRKQILFPEKSEDFRENIFQ
				YDDEGGGEEDTEAFDIAELR
				SSTIMRERKTRKTTSAEIRS
				LYRQSLQVGPDSAIFRKFIL
				EKLEEANTDPCAPPFDSLQT
				YAFEGTGSLAGSLSSLESAV
				SDQDESYDYLNELGPRFKRL
				ACMFGSAVQSNN

945	Human	Human	nt	atgaactgttatttactgct
	Cadherin-			gcgttttatgttgggaattc
	19			ctctcctatggccttgtctt
				ggagcaacagaaaactctca
				aacaaagaaagtcaagcagc
				cagtgcgatctcatttgaga
				gtgaagcgtggctgggtgtg
				gaaccaattttttgtaccag
				aggaaatgaatacgactagt
				catcacatcggccagctaag
				atctgatttagacaatggaa
				acaattctttccagtacaag
				cttttgggagctggagctgg
				aagtacttttatcattgatg
				aaagaacaggtgacatatat
				gccatacagaagcttgatag
				agaggagcgatccctctaca
				tcttaagagcccaggtaata
				gacatcgctactggaagggc
				tgtggaacctgagtctgagt
				ttgtcatcaaagtttcggat
				atcaatgacaatgaaccaaa
				attcctagatgaaccttatg
				aggccattgtaccagagatg
				tctccagaaggaacattagt
				tatccaggtgacagcaagtg
				atgctgacgatccctcaagt
				ggtaataatgctcgtctcct
				ctacagcttacttcaaggcc
				agccatatttttctgttgaa
				ccaacaacaggagtcataag
				aatatcttctaaaatggata
				gagaactgcaagatgagtat
				tgggtaatcattcaagccaa
				ggacatgattggtcagccag
				gagcgttgtctggaacaaca
				agtgtattaattaaactttc
				agatgttaatgacaataagc
				ctatatttaaagaaagttta
				taccgcttgactgtctctga
				atctgcacccactgggactt
				ctacaggaacaatcatggca
				tatgataatgacataggaga
				gaatgcagaaatggattaca
				gcattgaagaggatgattcg
				caaacatttgacattattac
				taatcatgaaactcaagaag
				gaatagttatattaaaaaag
				aaagtggatcttgagcacca
				gaaccactacggtattagag
				caaaagttaaaaaccatcat
				gttcctgagcagctcatgaa
				gtaccacactgaggcttcca
				ccactttcattaagatccag
				gtggaagatgttgatgagcc
				tcctcttttcctccttccat
				attatgtatttgaagttttt
				gaagaaaccccacagggatc
				atttgtaggcgtggtgtctg
				ccacagacccagacaatagg
				aaatctcctatcaggtattc
				tattactaggagcaaagtgt
				tcaatatcaatgataatggt
				acaatcactacaagtaactc
				actgcatcgtgaaatcagtg
				cttggtacaacctaagtatt
				acagccacagaaaaatacaa
				tatagaacagatctcttcga
				tcccactgtatgtgcaagtt
				cttaacatcaatgatcatgc
				tcctgagttctctcaatact
				atgagacttatgtttgtgaa
				aatgcaggctccggtcaggt
				aattcagactatcagtgcag
				tggatagagatgaatccata
				gaagagcaccatttttactt
				taatctatctgtagaagaca
				ctaacaattcaagttttaca
				atcatagataaccaagataa
				cacagctgtcattttgacta
				atagaactggttttaacctt
				caagaagaacctgtcttcta
				catctccatcttaattgccg
				acaatggaatcccgtcactt
				acaagtacaaacacccttac
				catccatgtctgtgactgtg
				gtgacagtgggagcacacag
				acctgccagtaccaggagct
				tgtgctttccatgggattca
				agacagaagtcatcattgct
				attctcatttgcattatgat
				catatttgggtttatttttt
				tgactttgggtttaaaacaa
				cggagaaaacagattctatt
				tcctgagaaaag
				tgaagatttcagagagaata
				tattccaatatgatgatgaa
				gggggtggagaagaagatac
				agaggcctttgatatagcag
				agctgaggagtagtaccata
				atgcgggaacgcaagactcg
				gaaaaccacaagcgctgaga
				tcaggagcctatacaggcag
				tctttgcaagttggccccga
				cagtgccatattcaggaaat
				tcattctggaaaagctcgaa
				gaagctaatactgatccgtg
				tgcccctccttttgattccc
				tccagacctacgcttttgag
				ggaacagggtcattagctgg
				atccctgagctccttagaat
				cagcagtctctgatcacgat
				gaaagctatgattaccttaa
				tgagttgggacctcgcttta
				aaagattagcatgcatgttt
				ggttctgcagtgcagtcaaa
				taattag

946	Cyno	Macaca	aa	MNCYLLLPFMLGIPLLWPCL
	Cadherin-	fasci-		GATENSQTKKVQQPVGSHLR
	19	cularis		VKRGWVWNQFFVPEEMNTTS
				HHVGRLRSDLDNGNNSFQYK
				LLGAGAGSTFIIDERTGDIY
				AIEKLDREERSLYILRAQVI
				DITTGRAVEPESEFVIKVSD
				INDNEPKFLDEPYEAIVPEM
				SPEGTLVIQVTASDADDPSS
				GNNARLLYSLLQGQPYFSVE
				PTTGVIRISSKMDRELQDEY
				WVIIQAKDMIGQPGALSGTT
				SVLIKLSDVNDNKPIFKESL
				YRLTVSESAPTGTSIGTIMA
				YDNDIGENAEMDYSIEEDDS
				QTFDIITNHETQEGIVILKK
				KVNFEHQNHYGIRAKVKNHH
				VDEQLMKYHTEASTTFIKIQ
				VEDVDEPPLFLLPYYIFEIF
				EETPQGSFVGVVSATDPDNR
				KSPIRYSITRSKVFNIDDNG
				TITTTNSLDREISAWYNLSI
				TATEKYNIEQISSIPVYVQV
				LNINDHAPEFSQYYESYVCE
				NAGSGQVIQTISAVDRDESI
				EEHHFYFNLSVEDTNSSSFT
				IIDNQDNTAVILTNRTGFNL
				QEEPIFYISILIADNGIPSL
				TSTNTLTIHVCDCDDSGSTQ
				TCQYQELMLSMGFKTEVIIA
				ILICIMVIFGFIFLTLGLKQ
				RRKQILFPEKSEDFRENIFR
				YDDEGGGEEDTEAFDVAALR
				SSTIMRERKTRKTTSAEIRS
				LYRQSLQVGPDSAIFRKFIL
				EKLEEADTDPCAPPFDSLQT
				YAFEGTGSLAGSLSSLESAV
				SDQDESYDYLNELGPRFKRL
				ACMFGSAVQSNN

947	Cyno	Macaca	nt	ATGAATTGTTATTTACTGCT
	Cadherin-	fasci-		GCCTTTTATGTTGGGAATTC
	19	cularis		CTCTCCTATGGCCTTGTCTT
				GGAGCAACAGAAAACTCTCA
				AACAAAGAAAGTCCAGCAGC
				CAGTAGGATCTCATCTGAGA
				GTGAAGCGTGGCTGGGTGTG
				GAACCAATTTTTTGTACCAG
				AGGAAATGAATACGACTAGT
				CATCACGTTGGCCGGCTAAG
				ATCTGATTTAGACAATGGAA
				ACAATTCTTTCCAGTACAAG
				CTTTTGGGAGCTGGAGCTGG
				AAGTACTTTTATCATTGATG
				AAAGAACAGGTGACATATAT
				GCCATAGAGAAGCTTGATAG
				AGAGGAGCGATCCCTCTACA
				TCTTAAGAGCCCAGGTAATA
				GACATCACTACTGGAAGGGC
				TGTGGAACCTGAGTCTGAGT
				TTGTCATCAAAGTTTCGGAT
				ATCAATGACAATGAACCAAA
				ATTCCTAGATGAACCTTATG
				AGGCCATTGTACCAGAGATG
				TCTCCAGAAGGAACATTAGT
				CATCCAGGTGACAGCAAGTG
				ATGCTGATGACCCTTCAAGT
				GGTAATAATGCTCGTCTCCT
				CTACAGCTTATTACAAGGCC
				AGCCATATTTTTCTGTTGAA
				CCAACAACAGGAGTCATAAG
				AATATCTTCTAAAATGGATA
				GAGAACTGCAAGATGAGTAT
				TGGGTAATCATTCAAGCCAA
				GGACATGATTGGTCAGCCAG
				GAGCGTTGTCTGGAACAACG
				AGTGTATTAATTAAACTTTC
				AGATGTTAATGACAATAAGC
				CTATATTTAAAGAAAGTTTA
				TACCGCCTGACGGTCTCTGA
				ATCTGCACCCACTGGGACTT
				CTATAGGAACAATCATGGCA
				TATGATAATGACATAGGAGA
				GAATGCAGAAATGGATTACA
				GCATTGAAGAGGATGATTCA
				CAGACATTTGACATTATTAC
				TAATCATGAAACTCAAGAAG
				GAATAGTTATATTAAAAAAG
				AAAGTGAATTTTGAGCACCA
				GAACCACTATGGTATTAGAG
				CAAAAGTTAAAAACCATCAT
				GTTGATGAGCAGCTCATGAA
				ATACCACACTGAAGCTTCCA
				CCACTTTCATTAAGATCCAG
				GTGGAAGATGTTGATGAGCC
				TCCTCTTTTCCTCCTTCCGT
				ATTACATATTTGAAATTTTT
				GAAGAAACCCCACAAGGATC
				ATTTGTAGGCGTGGTGTCTG
				CCACAGACCCAGACAATAGG
				AAATCTCCTATCAGGTATTC
				TATTACTAGGAGCAAAGTGT
				TCAATATCGATGATAATGGT
				ACAATCACTACAACTAACTC
				ACTGGATCGGGAAATCAGTG
				CTTGGTACAACCTAAGTATT
				ACAGCCACAGAAAAATACAA
				TATAGAGCAGATCTCTTCGA
				TCCCAGTGTATGTGCAAGTT
				CTTAATATCAATGATCATGC
				TCCTGAGTTCTCTCAATACT
				ATGAGAGTTATGTTTGTGAA
				AATGCAGGCTCTGGTCAGGT
				AATTCAGACTATCAGTGCAG
				TGGATAGAGATGAATCCATA
				GAAGAGCACCATTTTTACTT
				TAATCTATCTGTAGAAGACA
				CTAACTCTTCAAGTTTTACA
				ATCATAGACAATCAAGATAA
				CACAGCTGTCATTTTGACTA
				ATAGAACTGGTTTTAACCTT
				CAAGAAGAGCCCATCTTCTA
				CATCTCCATCTTAATTGCCG
				ACAATGGAATCCCGTCACTT
				ACAAGTACAAACACCCTTAC
				CATCCATGTCTGTGACTGTG
				ATGACAGTGGGAGCACACAG
				ACCTGCCAGTACCAGGAGCT
				TATGCTTTCCATGGGATTCA
				AGACAGAAGTCATCATTGCT
				ATTCTCATTTGCATTATGGT
				AATATTTGGGTTTATTTTTT
				TGACTTTGGGTTTAAAACAA
				CGGAGAAAACAGATTCTATT
				TCCTGAGAAAAG
				TGAAGATTTCAGAGAGAATA
				TATTCCGATATGATGACGAA
				GGGGGTGGAGAAGAAGATAC
				AGAGGCCTTTGACGTAGCAG
				CGCTGAGGAGTAGCACCATA
				ATGCGGGAACGCAAGACTCG
				GAAAACCACCAGCGCTGAGA
				TCAGGAGCCTATACAGGCAG
				TCTTTGCAAGTTGGCCCCGA
				CAGTGCCATATTCAGGAAGT
				TCATCCTGGAAAAGCTCGAA
				GAAGCTGATACTGATCCGTG
				TGCCCCTCCTTTTGATTCCC
				TCCAGACCTACGCTTTTGAG
				GGAACAGGGTCATTAGCTGG
				ATCCCTGAGCTCCTTAGAAT
				CAGCTGTCTCTGATCAGGAT
				GAAAGCTATGATTACCTTAA
				CGAGTTGGGACCTCGCTTTA
				AAAGATTAGCATGCATGTTT
				GGTTCTGCAGTGCAGTCAAA
				TAATTAG

948	secreted	Human	aa	MNCYLLLRFMLGIPLLWPCL
	Cadherin-			GATENSQTKKVKQPVRSHLR
	19			VKRGWVWNQFFVPEEMNTTS
	ecto-			HHIGQLRSDLDNGNNSFQYK
	domain			LLGAGAGSTFIIDERTGDIY
	(amino			AIQKLDREERSLYILRAQVI
	acids			DIATGRAVEPESEFVIKVSD
	1-596)			INDNEPKFLDEPYEAIVPEM
				SPEGTLVIQVTASDADDPSS
				GNNARLLYSLLQGQPYFSVE
				PTTGVIRISSKMDRELQDEY
				WVIIQAKDMIGQPGALSGTT
				SVLIKLSDVNDNKPIFKESL
				YRLTVSESAPTGTSIGTIMA
				YDNDIGENAEMDYSIEEDDS
				QTFDIITNHETQEGIVILKK
				KVDFEHQNHYGIRAKVKNHH
				VPEQLMKYHTEASTTFIKIQ
				VEDVDEPPLFLLPYYVFEVF
				EETPQGSFVGVVSATDPDNR
				KSPIRYSITRSKVFNINDNG
				TITTSNSLDREISAWYNLSI
				TATEKYNIEQISSIPLYVQV
				LNINDHAPEFSQYYETYVCE
				NAGSGQVIQTISAVDRDESI
				EEHHFYFNLSVEDTNNSSFT
				IIDNQDNTAVILTNRTGFNL
				QEEPVFYISILIADNGIPSL
				TSTNTLTIHVCDCGDSGSTQ
				TCQYQELVLSMGFKTE

949	secreted	Human	nt	atgaactgttatttactgct
	Cadherin-			gcgttttatgttgggaattc
	19			ctctcctatggccttgtctt
	ecto-			ggagcaacagaaaactctca
	domain			aacaaagaaagtcaagcagc
	(amino			cagtgcgatctcatttgaga
	acids			gtgaagcgtggctgggtgtg
	1-596)			gaaccaattttttgtaccag
				aggaaatgaatacgactagt
				catcacatcggccagctaag
				atctgatttagacaatggaa
				acaattctttccagtacaag
				cttttgggagctggagctgg
				aagtacttttatcattgatg
				aaagaacaggtgacatatat
				gccatacagaagcttgatag
				agaggagcgatccctctaca
				tcttaagagcccaggtaata
				gacatcgctactggaagggc
				tgtggaacctgagtctgagt
				ttgtcatcaaagtttcggat
				atcaatgacaatgaaccaaa
				attcctagatgaaccttatg
				aggccattgtaccagagatg
				tctccagaaggaacattagt
				tatccaggtgacagcaagtg
				atgctgacgatccctcaagt
				ggtaataatgctcgtctcct
				ctacagcttacttcaaggcc
				agccatatttttctcttgaa
				ccaacaacaggagtcataag
				aatatcttctaaaatggata
				gagaactgcaagatgagtat
				tgggtaatcattcaagccaa
				ggacatgattggtcagccag
				gagcgttgtctggaacaaca
				agtgtattaattaaactttc
				agatgttaatgacaataagc
				ctatttttaaagaaagttta
				taccgcttgactgtctctga
				atctgcacccactgggactt
				ctataggaacaatcatggca
				tatgataatgacataggaga
				gaatgcagaaatggattaca
				gcattgaagaggatgattcg
				caaacatttgacattattac
				taatcatgaaactcaagaag
				gaatagttatattaaaaaag
				aaagtggattttgagcacca
				gaaccactacggtattagag
				caaaagttaaaaaccatcat
				gttcctgagcagctcatgaa
				gtaccacactgaggcttcca
				ccactttcattaagatccag
				gcggaagatgttgatgagcc
				tcctcttttcctccttccat
				attatgtatttgaagttttt
				gaagaaaccccacagggatc
				atttgtaggcgtggtgtctg
				ccacagacccagacaatagg
				aaatctcctatcaggtattc
				tattactaggagcaaagtgt
				tcaatatcaatgacaatggt
				acaatcactacaagtaactc
				actggatcgtgaaatcagtg
				cttggtacaacctaagtatt
				acagccacagaaaaatacaa
				tatagaacagatctcttcga
				tcccactgtatgtgcaagtt
				cttaacatcaatgatcatgc
				tcctgagttctctcaatact
				atgagacttatgtttgtgaa
				aatgcaggctctggtcaggt
				aattcagactatcagtgcag
				tggatagagatgaatccata
				gaagagcaccatttttactt
				taatctatctgtagaagaca
				ctaacaattcaagttttaca
				atcatagataatcaagataa
				cacagctgtcattttgacta
				atagaactggttttaacctt
				caagaagaacctgtcttcta
				catctccatcttaattgccg
				acaatggaatcccgtcactt
				acaagtacaaacacccttac
				catccatgtctgtgactgtg
				gtgacagtgggagcacacag
				acctgccagtaccaggagct
				tgtgctttccatgggattca
				agacagaa

950	truncated	Human	aa	MNCYLLLRFMLGIPLLWPCL
	membrane			GATENSQTKKVKQPVRSHLR
	bound			VKRGWVWNQFFVPEEMNTTS
	form			HHIGQLRSDLDNGNNSFQYK
	of human			LLGAGAGSTFIIDERTGDIY
	cadherin-			AIQKLDREERSLYILRAQVI
	19			DIATGRAVEPESEFVIKVSD
	(amino			INDNEPKFLDEPYEAIVPEM
	acids			SPEGTLVIQVTASDADDPSS
	1-624)			GNNARLLYSLLQGQPYFSVE
				PTTGVIRISSKMDRELQDEY
				WVIIQAKDMIGQPGALSGTT
				SVLIKLSDVNDNKPIFKE
				SLYRLTVSESAPTGTSIGTI
				MAYDNDIGENAEMDYSIEED
				DSQTFDIITNHETQEGIVIL
				KKKVDFEHQNHYGIRAKVKN
				KHVPEQLMKYHTEASTTFIK
				IQVEDVDEPPLFLLPYYVFE
				VFEETPQGSFVGVVSATDPD
				NRKSPIRYSITRSKVFNIND
				NGTITTSNSLDREISAWYNL
				SITATEKYNIEQISSIPLYV
				QVLNINDHAPEFSQYYETYV
				CENAGSGQVIQTISAVDRDE
				SIEEHHFYFNLSVEDTNNSS
				FTIIDNQDNTAVILTNRTGF
				NLQEEPVFYISILIADNGIP
				SLTSTNTLTIHVCDCGDSGS
				TQTCQYQELVLSMGFKTEVI
				IAILICIMIIFGFIFLTLGL
				KQRRKQ

951	truncated	Humanl	nt	atgaactgttatttactgct
	membrane			gcgttttatgttgggaattc
	bound			ctctcctatggccttgtctt
	form of			ggagcaacagaaaactctca
	human			aacaaagaaagtcaagcagc
	cadherin-			cagtgcgatctcatttgaga
	19			gtgaagcgtggctgggtgtg
	(amino			gaaccaattttttgtaccag
	acids			aggaaatgaatacgactagt
	1-624)			catcacatcggccagctaag
				atctgatttagacaatggaa
				acaattctttccagtacaag
				cttttgggagctggagctgg
				aagtacttttatcattgatg
				aaagaacaggtgacatatat
				gccatacagaagcttgatag
				agaggagcgatccctctaca
				tcttaagagcccaggtaata
				gacatcgctactggaagggc
				tgtggaacctgagtctgagt
				ttgtcatcaaagtttcggat
				atcaatgacaatgaaccaaa
				attcctagatgaaccttatg
				aggccattgtaccagagatg
				tctccagaaggaacattagt
				tatccaggtgacagcaagtg
				atgctgacgatccctcaagt
				ggtaataatgctcgtctcct
				ctacagcttacttcaaggcc
				agccatatttttctgttgaa
				ccaacaacaggagtcataag
				aatatcttctaaaatggata
				gagaactgcaagatgagtat
				tgggtaatcattcaagccaa
				ggacatgattggtcagccag
				gagcgttgtctggaacaaca
				agtgtattaattaaactttc
				agatgttaatgacaataagc
				ctatatttaaagaaagttta
				taccgcttgactgtctctga
				atctgcacccactgggactt
				ctataggaacaatcatggca
				tatgataatgacataggaga
				gaatgcagaaatggattaca
				gcattgaagaggatgattcg
				caaacatttgacattattac
				taatcatgaaactcaagaag
				gaatagttatattaaaaaag
				aaagtggattttgagcacca
				gaaccactacggtattagag
				caaaagttaaaaaccatcat
				gttcctgagcagctcatgaa
				gtaccacactgaggcttcca
				ccactttcattaagatccag
				gtggaagatgttgatgagcc
				tcctcttttcctccttccat
				attatgtatttgaagttttt
				gaagaaaccccacagggatc
				atttgtaggcgtggtgtctg
				ccacagacccagacaatagg
				aaatctcctatcaggtattc
				tattactaggagcaaagtgt
				tcaatatcaatgataatggt
				acaatcactacaagtaactc
				actggatcgtgaaatcagtg
				cttggtacaacctaagtatt
				acagccacagaaaaatacaa
				tatagaacagatctcttcga
				tcccactgtatgtgcaagtt
				cttaacatcaatgatcatgc
				tcctgagttctctcaatact
				atgagacttatgtttgtgaa
				aatgcaggctctggtcaggt
				aattcagactatcagtgcag
				tggatagacatgaatccaLa
				gaagagcaccatttttactt
				taatctatctgtagaagaca
				ctaacaattcaagttttaca
				atcatagataatcaagataa
				cacagctgtcattttgacta
				atagaactggttttaacctt
				caagaagaacctgtcttcta
				catctccatcttaattgccg
				acaatggaatcccgtcactt
				acaagtacaaacacccttac
				catccatgtctgtgactgtg
				gtgacagtgggagcacacag
				acctgccagtaccaggagct
				tgtgctttccatgggattca
				agacagaagtcatcattgct
				attctcatttgcattatgat
				catatttgggtttatttttt
				tgactttgggtttaaaacaa
				cggagaaaacag

952	C137897	artifi-	aa	GWVWNQFFVPEEMNTTSHHI
	huCDH19	cial		GQLRSDLDNGNNSFQYKLLG
	(44-141)			AGAGSTFIIDERTGDIYAIQ
	muCDH19			KLDREERSLYILRAQVIDIA
	(140-770)			TGRAVEPESEFVIKVSDIND
				NEPRFLDEPYEAIVPEMSPE
				GTFVIKVTANDADDPSTGYH
				ARILYNLERGQPYFSVEPTT
				GVIRISSKMDRELQDTYCVI
				IQAKDMLGQPGALSGTTTVS
				IKLSDINDNKPIFKESFYRF
				TISESAPIGTSIGKIMAYDD
				DIGENAEMEYSIEDDDSKIF
				DIIIDMDTQEGIVILKKKVD
				FEQQSYYGIRAKVKNCHVDE
				ELAPAHVNASTTYIKVQVED
				EDEPPVFLLPYYILEIPEGK
				PYGTIVGTVSATDPDRRQSP
				MRYYLTGSKMFDINDNGTII
				TTNMLDREVSAWYNLTVTAT
				ETYNVQQISSAHVYVQVFNI
				NDNAPEFSQFYETYVCENAE
				SGEIVQIISAIDRDESIEDH
				HFYFNHSLEDTNNSSFMLTD
				NQDNTAVILSNRTGFNLKEE
				PVFYMIILIADNGIPSLTST
				NTLTIQVCDCGDSRNTETCA
				NKGLLFIMGFRTEAIIAIMI
				CVMVIFGFFFLILALKQRRK
				ETLFPEKTEDFRENIFCYDD
				EGGGEEDSEAFDIVELRQST
				VMRSRKPQRSKSAEIRSLYR
				QSLQVGPDSAIFRKFILEKL
				SEAMTDPCAPPFDSLQTFAY
				EGTGSSAGSLSSLASRDTDQ
				EDDFDYLNDLGPRFKRLASM
				FGSAVQPNN

953	C137897	artifi-	nt	ggctgggtgtggaaccaatt
	huCDH19	cial		ttttgtaccagaggaaatga
	(44-141)			atacgactagtcatcacatc
	muCDH19			ggccagctaagatctgattt
	(140-770)			agacaatggaaacaattctt
				tccagtacaagcttttggga
				gctggagctggaagtacttt
				tatcattgatgaaagaacag
				gtgacatatatgccatacag
				aagcttgatagagaggagcg
				atccctctacatcttaagag
				cccaggtaatagacatcgct
				actggaagggctgtggaacc
				tgagtctgagtttgtcatca
				aagtttcggatatcaatgac
				aatgaacccagattcctaga
				tgaaccatatgaggccattg
				tacctgagatgtctccagaa
				ggaacatttgtcatcaaggt
				gacagccaatgacgcagatg
				atccttcaactggctatcat
				gctcgcatcctatacaactt
				agaacgaggtcaaccatact
				tttctgttgagccaacaaca
				ggagtcataaggatatcttc
				taagatggatagagagttgc
				aagatacatactgtgtaatt
				attcaagccaaggacatgct
				cggtcagcctggagccttgt
				ctggaacaacaaccgtatca
				attaagctgtcagatattaa
				tgacaacaagccaatattca
				aagaaagtttctaccgcttc
				actatatctgaatctgcacc
				cattggaacatcaataggga
				aaattatggcatatgatgat
				gacataggggagaatgcaga
				gatggagtacagcattgaag
				atgatgattcaaaaatattt
				gacataatcattgacaatga
				cacccaagaagggatagtta
				tacttaaaaagaaagttgat
				tttgagcagcagagctatta
				tggcattagagctaaggtta
				aaaactgccatgtggatgaa
				gagcttgcacctgcccatgt
				taacgcttccacaacctaca
				ttaaagttcaagtagaagat
				gaagatgaacctcctgtttt
				cctcttaccatattacatac
				ttgaaattcctgaaggaaaa
				ccatatggaacaattgtggg
				gacggtttctgccacagacc
				cagatcgaagacaatctcct
				atgagatattatctcactgg
				aagcaaaatgtttgatatca
				atgacaatggaacaataatc
				accactaacatgcttgacag
				agaggtcagtgcttggtaca
				acttgactgtcacagctact
				gaaacatacaatgtacaaca
				gatctcttcagcccatgttt
				atgtacaagtctttaacatt
				aacgacaatgctccagagtt
				ctctcaattctatgagactt
				atgtttgtgaaaatgctgaa
				tctggtgagatagttcagat
				catcagtgcaattgatagag
				atgagtccatagaagatcac
				catttttactttaatcactc
				tctggaagacacaaacaact
				caagttttatgctaacagac
				aatcaagataacacagctgt
				aattctgagtaatagaactg
				gtttcaatcttaaagaagag
				cctgtcttctacattgatca
				tcttgattgctgataacggga
				tcccatctctcacaagcaca
				aacactctcactatccaagt
				ctgtgactgtggagacagta
				gaaacacagaaacttgtgct
				aacaagggacttctctttat
				catgggattcagaacagagg
				caataattgccatcatgata
				tgtgttatggtaatatttgg
				gtttttctttttgattcttg
				ctctgaaacagcgaagaaag
				gagactctatttccagagaa
				gactgaagactttagggaga
				atatattttgctatgatgat
				gaaggcggcggggaagaaga
				ctcggaagcctttgacatcg
				tagagctgagacaaagtaca
				gtaatgagagaaagaaagcc
				tcagagaagcaagagtgcgg
				agatcaggagcttgtacagg
				cagtccctgcaggtgggccc
				agacagtgccatatttcgaa
				aatttatcccagagaagctt
				gaagaagccaacacagaccc
				atgtgctcccccctttgatt
				cactacagacgtttgcctat
				gagggaacagggtcaicagc
				tggctctctgagctccttgg
				catccagagacactgatcag
				gaggatgacttcgactacct
				taatgacctgggacctcgtt
				ttaaaagattagcaagcatg
				tttggctctgcagtacaacc
				caacaattag

954	C137896	artifi-	aa	GWVWNQFFVPEEMNTTSHHI
	huCDH19	cial		GQLRSDLDNGNNSFQYKLLG
	(44-249)			AGAGSTFIIDERTGDIYAIQ
	muCDH19			KLDREERSLYILRAQVIDIA
	(248-770)			TGRAVEPESEFVIKVSDIND
				NEPKFLDSPYEAIVPEMSPE
				GTLVIQVTASDADDPSSGNN
				ARLLYSLLQGQPYFSVEPTT
				GVIRISSKMDRELQDEYWVI
				IQAKDMIGQPGALSGTTSVL
				IKLSDVNDNKPIFKESFYRF
				TISESAPIGTSIGKIMAYDD
				DIGENAEMEYSIEDDDSKIF
				DIIIDNDTQEGIVILKKKVD
				FEQQSYYGIRAKVKNCHVDE
				ELAPAHVNASTTYIKVQVED
				EDEPPVFLLPYYILEIPEGK
				PYGTIVGTVSATDPDRRQSP
				MRYYLTGSKMFDINDNGTII
				TTNMLDREVSAWYNLTVTAT
				ETYNVQQISSAHVYVQVFNI
				NDNAPEFSQFYETYVCENAE
				SGEIVQIISAIDRDESIEDH
				HFYFNHSLEDTNNSSFMLTD
				NQDNTAVILSNRTGFNLKEE
				PVFYMIILIADNGIPSLTST
				NTLTIQVCDCGDSRNTETCA
				NKGLLFIMGFRTEAIIAIMI
				CVMVIFGFFFLILALKQRRK
				ETLFPEKTEDFRENIFCYDD
				EGGGEEDSEAFDIVELRQST
				VMRERKPQRSKSAEIRSLYR
				QSLQVGPDSAIFRKFILEKL
				SEANTDPCAPPFDSLQTFAY
				EGTGSSAGSLSSLASRDTDQ
				EDDFDYLNDLGPRFKRLASM
				FGSAVQPNH

955	C137896	artifi-	nt	ggctgggtgtggaaccaatt
	huCDH19	cial		ttttgtaccagaggaaatga
	(44-249)			atacgactagtcatcacatc
	muCDH19			ggccagctaagatctgattt
	(248-770)			agacaa
				tggaaacaattctttccagt
				acaagcttttgggagctgga
				gctggaagtacttttatcat
				tgatgaaagaacaggttgac
				atatatgccatacagaagct
				tgatagagaggagcgatccc
				tctacatcttaagagcccag
				gtaatagacatcgctactgg
				aagggctgtggaacctgagt
				ctgagtttgtcatcaaagtt
				tcggatatcaatgacaatga
				accaaaattcctagatgaac
				cttatgaggccattgtacca
				gagatgtctccagaaggaac
				attagttatccaggtgacag
				caagtgatgctgacgatccc
				tcaagtggtaataatgctcg
				tctcctctacagcttacttc
				aaggccagccatatttttct
				gttgaaccaacaacaggagt
				cataagaatatcttctaaaa
				tggatagagaactgcaagat
				gagtattgggtaatcattca
				agccaaggacatgattggtc
				agccaggagcgttgtctgga
				acaacaagtgtattaattaa
				actttcagatgttaatgaca
				acaagccaatattcaaagaa
				agtttctaccgcttcactat
				atctgaatctgcacccattg
				gaacatcaatagggaaaatt
				atggcatatgatgatgacat
				aggggagaatgcagagatgg
				agtacagcattgaagatgat
				gattcaaaaatatttgacat
				aatcattgacaatgacaccc
				aagaagggatagttatactt
				aaaaagaaagttgattttga
				gcagcagagctattatggca
				ttagagctaaggttaaaaac
				tgccatgtggatgaagagct
				tgcacctgcccatgttaacg
				cttccacaacctacattaaa
				gttcaagtagaagatgaaga
				tgaacctcctgttttcctct
				taccatattacatacttgaa
				attcctgaaggaaaacca~a
				tggaacaattgtggggacgg
				tttctgccacagacccagat
				cgaagacaatctcctatgag
				atattatctcactggaagca
				aaatgtttgatatcaatgac
				aatggaacaataatcaccac
				taacatgcttgacagagagg
				tcagtgcttggtacaacttg
				actgtcacagctactgaaac
				atacaatgtacaacagatct
				cttcagcccatgtttatgta
				caagtctttaacattaacga
				caatgctccagagttctctc
				aattctatgagacttatgtt
				tgtgaaaatgctgaatctgg
				tgagatagttcagatcatca
				gtgcaattgatagagatgag
				tccatagaagatcaccattt
				ttactttaatcactctctgg
				aagacacaaacaactcaagt
				tttatgctaacagacaatca
				agataacacagctgtaattc
				tgagtaatagaactggtttc
				aatcttaaagaagagcctgt
				cttctacatgatcatcttga
				ttgctgataacgggatccca
				tctctcacaagcacaaacac
				tctcactatccaagtctgtg
				actgtggagacagtacaaac
				acagaaacttgtgctaacaa
				gcgacttctctttatcatgg
				gattcagaacagaggcaata
				attgccatcatgatatgtgt
				tatggtaatatttgggtttt
				tctttttgattcttgctctg
				aaacagcgaagaaaggagac
				tctatttccagagaagactg
				aagactttagggagaatata
				ttttgctatgatgatgaagg
				cggcggggaagaagactcgg
				aagcctttgacatcgtagag
				ctgagacaaagtacagtaat
				gagagaaagaaagcctcaga
				gaagcaagagtgcggagatc
				aggagcttgtacaggcagtc
				cctgcaggtgggcccagaca
				gtgccatatttcgaaaattt
				atcctagagaagcttgaaga
				agccaacacagacccatgtg
				ctcccccctttgattcacta
				cagacgtttgcctatgaggg
				aacagggtcatcagctggct
				ctctgagctccttggcatcc
				agagacactgatcaggagga
				tgacttcgactaccttaatg
				acctgggacctcgttttaaa
				agattagcaagcatgtttgg
				ctctgcagtacaacccaaca
				attag

956	C137913	artifi-	aa	AWVWRPFVVLEEMDDIQCVG
	muCDH19	cial		KLRSDLDNGNNSFQYKLLGI
	(44-139)			GAGSFSINERTGEICAIQKL
	huCDH19			DREEKSLYILRAQVIDTTIG
	(142-249)			KAVETESEFVIRVLDINDNE
	muCDH19			PKFLDEPYEAIVPEMSPEGT
	(248-770)			LVIQVTASDADDPSSGNNAR
				LLYSLLQGQPYFSVEPTTGV
				IRISSKMDRELQDEYWVIIQ
				AKDMIGQPGALSGTTSVLIK
				LSDVNDNKPIFKESFYRFTI
				SESAPIGTSIGKIMAYDDDI
				GENAEMEYSIEDDDSKIFDI
				IIDNDTQEGIVILKKKVDFE
				QQSYYGIRAKVKNCHVDEEL
				APAHVNASTTYIKVQVEDED
				EPPVFLLPYYILEIPEGKPY
				GTIVGTVSATDPDRRQSPMR
				YYLTGSKMFDINDNGTIITT
				NMLDREVSAWYNLTVTATET
				YNVQQISSAHVYVQVFNIND
				NAPEFSQFYETYVCENAESG
				EIVQIISAIDRDESIEDHHF
				YFNHSLEDTNNSSFMLTDNQ
				DNTAVILSNRTGFNLKEEPV
				FYMIILIADNGIPSLTSTNT
				LTIQVCDCGDSRNTETCANK
				GLLFIMGFRTEAIIAIMICV
				MVIFGFFFLILALKQRRKET
				LFPEKTEDFRENIFCYDDEG
				GGEEDSEAFDIVELRQSTVM
				RERKPQRSKSAEIRSLYRQS
				LQVGPDSAIFRKFILEKLEE
				ANTDPCAPPFDSLQTFAYEG
				TGSSAGSLSSLASRDTDQED
				DFDYLNDLGPRFKRLASMFG
				SAVQPNN

957	C137913	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgttgttctagaagaaatgg
	(44-139)			atgatatacaatgtgttgga
	huCDH19			aagctaagatctgacttaga
	(142-249)			caatggaaacaactctttcc
	muCDH19			agtacaagctactggggatt
	(248-770)			ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatac
				agaagcttgatagagaggaa
				aaatccctctacattctgag
				agcccaggtaatagacacca
				ctattgggaaggctgtggaa
				actgaatccgagtttgtcat
				cagagttttggatatcaatg
				acaatgaaccaaaattccta
				gatgaaccttatgaggccat
				tgtaccagagatgtctccag
				aaggaacattagttatccag
				gtgacagcaagtgatgctga
				cgatccctcaagtggtaata
				atgctcgtctcctctacagc
				ttacttcaaggccagccata
				tttttctgttgaaccaacaa
				caggagtcataagaatatct
				tctaaaatggatagagaact
				gcaagatgagtattgggtaa
				tcattcaagccaaggacatg
				attggtcagccaggagcgtt
				gtctggaacaacaagtgtat
				taattaaactttcagatgtt
				aatgacaacaagccaatatt
				caaagaaagtttctaccgct
				tcactatatctgaatctgca
				cccattggaacatcaatagg
				gaaaattatggcatatgatg
				atgacataggggagaatgca
				gagatggagtacagcattga
				agatgatgattcaaaaatat
				ttgacataatcattgacaat
				gacacccaagaagggatagt
				tatacttaaaaagaaagttg
				attttgagcagcagagctat
				tatggcattagagctaaggt
				taaaaactgccatgtggatg
				aagagcttgcacctgcccat
				gttaacgcttccacaaccta
				cattaaagttcaagtagaag
				atgaagatgaacctcctgtt
				ttcctcttaccatattacat
				acttgaaattcctgaaggaa
				aaccatatggaacaattgtg
				gggacggtttctgccacaga
				cccagatcgaagacaatctc
				ctatgagatattatctcact
				ggaagcaaaatgtttgatat
				caatgacaatggaacaataa
				tcaccactaacatgcttgac
				agagaggtcagtgcttggta
				caacttgactgtcacagcta
				ctgaaacatacaatgtacaa
				cagatctcttcagcccatgt
				ttatgtacaagtctttaaca
				ttaacgacaatgctccagag
				ttctctcaa-tctatgagac
				ttatgtttgtgaaaatgctg
				aatctggtgagatagttcag
				atcatcagtgcaattgatag
				agatgagtccatagaagatc
				accatttttactttaatcac
				tctctggaagacacaaacaa
				ctcaagttttatgctaacag
				acaatcaagataacacagct
				gtaattctgagtaatagaac
				tggtttcaatcttaaagaag
				agcctgtcttctacatgatc
				atcttgattgctgataacgg
				gatcccatctctcacaagca
				caaacactctcactatccaa
				gtctgtgactgtggagacag
				tagaaacacagaaacttgtg
				ctaacaagggacttctcttt
				atcatgggattcagaacaga
				ggcaacaattgccatcatga
				tatgtgttatggtaatattt
				gggtttttctttttgattct
				tgctctgaaacagcgaagaa
				aggagactctacttccagag
				aagactgaagactttaggga
				gaatatattttgctatgatg
				atgaaggcggcggggaagaa
				gactcggaagcctttgacat
				cgtagagctgagacaaagta
				cagcaatgagagaaagaaag
				cctcagagaagcaagagtgc
				ggagatcaggagcttgtaca
				ggcagtccctgcaggtgggc
				ccagacagtgccatatttcg
				aaaatttatcctagagaagc
				ttgaagaagccaacacagac
				ccatgtgctcccccctttga
				ttcactacagacgtttgcct
				atgagggaacagggtcatca
				gctggctctctgagctcctt
				ggcatccagagacactgatc
				aggaggatgacttcgactac
				cttaatgacctgggacctcg
				ttttaaaagattagcaagca
				tgtttggctctgcagtacaa
				cccaacaattag

958	C137847	artifi-	aa	AWVWRPFVVLEEMDDIQCVG
	muCDH19	cial		KLRSDLDNGNNSFQYKLLGI
	(44-139)			GAGSFSINERTGEICAIQKL
	huCDH19			DREEKSLYILRAQVIOTTIG
	(142-364)			KAVETESEFVIRVLDINDNE
	muCDH19			PKFLDEPYEAIVPEMSPEGT
	(363-770)			LVIQVTASDADDPSSGNNAR
				LLYSLLQGQPYFSVEPTTGV
				IRISSKMDRELQDEYWVIIQ
				AKDMIGQPGALSGTTSVLIK
				LSDVNDNKPIFKESLYRLTV
				SESAPTGTSIGTIMAYDNDI
				GENAEMDYSIEEDDSQTFDI
				ITNHETQEGIVILKKKVDFE
				HQNHYGIRAKVKNHHVPEQL
				MKYHTEASTTFIKIQVEDVD
				EPPVFLLPYYILEIPEGKPY
				GTIVGTVSATDPDRRQSPMR
				YYLTGSKMFDINDNGTIITT
				NMLDREVSAWYNLTVTATET
				YNVQQISSAHVYVQVFNIND
				NAPEFSQFYETYVCENAESG
				EIVQIISAIDRDESIEDHHF
				YFNHSLEDTNNSSFMLTDNQ
				DNTAVILSNRTGFNLKEEPV
				FYMIILIADNGIPSLTSTNT
				LTIQVCDCGDSRNTETCANK
				GLLFIMGFRTEAIIAIMICV
				MVIFGFFFLILALKQRRKET
				LFPEKTEDFRENIFCYDDEG
				GGEEDSEAFDIVELRQSTVM
				RERKPQRSKSAEIRSLYRQS
				LQVGPDSAIFRKFILEKLEE
				ANTDPCAPPFDSLQTFAYEG
				TGSSAGSLSSLASRDTDQED
				DFDYLNDLGPRFKRLASMFG
				SAVQPNN

959	C137847	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgttgttctagaagaaatgg
	(44-139)			atgatatacaatgtgttgga
	huCDH19			aagctaagatctgacttaga
	(142-364)			caatggaaacaactctttcc
	muCDH19			agtacaagctactggggatt
	(363-770)			ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatacagaagctt
				gatagagaggaaaaatccct
				ctacattctgagagcccagg
				taatagacaccactattggg
				aaggctgtggaaactgaatc
				cgagtttgtcatcagagttt
				tggatatcaatgacaatgaa
				ccaaaattcctagatgaacc
				ttatgaggccattgtaccag
				agatgtctccagaaggaaca
				ttagttatccaggtgacagc
				aagtgatgctgacgatccct
				caagtggtaataatgctcgt
				ctcctctacagcttacttca
				aggccagccatatttttctg
				ttgaaccaacaacaggagtc
				ataagaatatcttctaaaat
				ggatagagaactgcaagatg
				agtattgggtaatcattcaa
				gccaaggacatgattggtca
				gccaggagcgttgtctggaa
				caacaagtgtattaattaaa
				ctttcagatgttaatgacaa
				taagcctatatttaaagaaa
				gtttataccgcttgactgtc
				tctgaatctgcacccactgg
				gacttctataggaacaatca
				tggcatatgataatgacata
				ggagagaatgcagaaatgga
				ttacagcattgaagaggatg
				attcgcaaacatttgacatt
				attactaatcatgaaactca
				agaaggaatagttatattaa
				aaaagaaagtggattttgag
				caccagaaccactacggtat
				tagagcaaaagttaaaaacc
				atcatgttcctgagcagctc
				atgaagtaccacactgaggc
				ttccaccactttcattaaga
				tccaggtggaagatgttgat
				gaacctcctgttttcctctt
				accatattacatacttgaaa
				ttcctgaaggaaaaccatat
				ggaacaattgtggggacggt
				ttctgccacagacccagatc
				gaagacaatctcctatgaga
				tattatctcactggaagcaa
				aatgtttgatatcaatgaca
				atggaacaataatcaccact
				aacatgcttgacagagaggt
				cagtgcttggtacaacttga
				ctgtcacagctactgaaaca
				tacaatgtacaacagatctc
				ttcagcccatgtttatgtac
				aagtctttaacattaacgac
				aatgctccagagttctctca
				attctatgagacttatgttt
				gtgaaaatgctgaatctggt
				gagatagttcagatcatcag
				tgcaattgatagagatgagt
				ccatagaagatcaccatttt
				tactttaatcactctctgga
				agacacaaacaactcaagtt
				ttatgctaacagacaatcaa
				gataacacagctgtaattct
				gagtaatagaactggtttca
				atcttaaagaagagcctgtc
				ttctacatgatcatcttgat
				tgctgataacgggatcccat
				ctctcacaagcacaaacact
				ctcactatccaagtctgtga
				ctgtggagacagtagaaaca
				cagaaacttgtgctaacaag
				ggacttctctttatcatggg
				attcagaacagaggcaataa
				ttgccatcatgatatgtgtt
				atggtaatatttgggttttt
				ctttttgattcttgctctga
				aacagcgaagaaaggagact
				ctatttccagagaagactga
				agactttagggagaatatat
				tttgctatgatgatgaaggc
				ggcggggaagaagactcgga
				agcctttgacatcgtagagc
				tgagacaaagtacagtaatg
				agagaaagaaagcctcagag
				aagcaagagtgcggagatca
				ggagcttgtacaggcagtcc
				ctgcaggtgggcccagacag
				tgccatatttcgaaaattta
				tcctagagaagcttgaagaa
				gccaacacagacccatgtgc
				tcccccctttgattcactac
				agacgtttgcctatgaggga
				acagggtcatcagctggctc
				tctgagctccttggcatcca
				gagacactgatcaggaggat
				gacttcgactaccttaatga
				cctgggacctcgttttaaaa
				gattagcaagcatgtttggc
				tctgcagtacaacccaacaa
				ttag

960	C137911	artifi-	aa	AWVWRPFVVLEEMDDIQCVG
	muCDH19	cial		KLRSDLDNGNNSFQYKLLGI
	(44-247)			GAGSFSINERTGEICAIQKL
	huCDH19			DREEKSLYILRAQVIDTTIG
	(250-364)			KAVETESEFVIRVLDINDNE
	muCDH19			PRFLDEPYEAIVPEMSPEGT
	(363-770)			FVIKVTANDADDPSTGYHAR
				ILYNLERGQPYFSVEPTTGV
				IRISSKMDRELQDTYCVIIQ
				AKDMLGQPGALSGTTTVSIK
				LSDINDNKPIFKESLYRLTV
				SESAPTGTSIGTIMAYDNDI
				GENAEMDYSIEEDDSQTFDI
				ITNHETQEGIVILKKKVDFE
				HQNHYGIRAKVKNHHVPEQL
				MKYHTEASTTFIKIQVEDVD
				EPPVFLLPYYILEIPEGKPY
				GTIVGTVSATDPDRRQSPMR
				YYLTGSKMFDINDNGTIITT
				NMLDREVSAWYNLTVTATET
				YNVQQISSAHVYVQVFNIND
				NAPEFSQFYETYVCENAESG
				EIVQIISAIDRDESIEDHHF
				YFNHSLEDTNNSSFMLTDNQ
				DNTAVILSNRTGFNLKEEPV
				FYMIILIADNGIPSLTSTNT
				LTIQVCDCGDSRNTETCANK
				GLLFIMGFRTEAIIAIMICV
				MVIFGFFFLILALKQRRKET
				LFPEKTEDFRENIFCYDDEG
				GGEEDSEAFDIVELRQSTVM
				RERKPQRSKSAEIRSLYRQS
				LQVGPDSAIFRKFILEKLEE
				ANTDPCAPPFDSLQTFAYEG
				TGSSAGSLSSLASRDTDQED
				DFDYLNDLGPRF

961	C137911	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgttgttctagaagaaatgg
	(44-247)			atgatatacaatgtgttgga
	huCDH19			aagctaagatctgacttaga
	(250-364)			caatggaaacaactctttcc
	muCDH19			agtacaagctactggggatt
	(363-770)			ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatacagaagctt
				gatagagaggaaaaatccct
				ctacattctgagagcccagg
				taatagacaccactattggg
				aaggctgtggaaactgaatc
				cgagtttgtcatcagagttt
				tggatatcaatgacaatgaa
				cccagattcctagatgaacc
				atatgaggccattgtacctg
				agat
				gtctccagaaggaacatttg
				tcatcaaggtgacagccaat
				gacgcagatgatccttcaac
				tggctatcatgctcgcatcc
				tatacaacttagaacgaggt
				caaccatacttttctgttga
				gccaacaacaggagtcataa
				ggatatcttctaagatggat
				agagagttgcaagatacata
				ctgtgtaattattcaagcca
				aggacatgctcggtcagcct
				ggagccttgtctggaacaac
				aaccgtatcaattaagctgt
				cagatattaatgacaataag
				cctatatttaaagaaagttt
				ataccgcttgactgtctctg
				aatctgcacccactgggact
				tctataggaacaatcatggc
				atatgataatgacataggag
				agaatgcagaaatggattac
				agcattgaagaggatgattc
				gcaaacatttgacattatta
				ctaatcatgaaactcaagaa
				ggaatagttatattaaaaaa
				gaaagtggattttgagcacc
				agaaccactacggtattaga
				gcaaaagttaaaaaccatca
				tgttcctgagcagctcatga
				agtaccacactgaggcttcc
				accactttcattaagatcca
				ggtggaagatgttgatgaac
				ctcctgttttcctcttacca
				tattacatacttgaaattcc
				tgaaggaaaaccatatggaa
				caattgtggggacggtttct
				gccacagacccagatcgaag
				acaatctcctatgagatatt
				atctcactggaagcaaaatg
				tttgatatcaatgacaatgg
				aacaataatcaccactaaca
				tgcttgacagagaggtcagt
				gcttggtacaacttgactgt
				cacagctactgaaacataca
				atgtacaacagatctcttca
				gcccatgtttatgtacaagt
				ctttaacattaacgacaatg
				ctccagagttctctcaattc
				tatgagacttatgtttgtga
				aaatgctgaatctggtgaga
				tagttcagatcatcagtgca
				attgatagagatgagtccat
				agaagatcaccatttttact
				ttaatctatctgtagaagac
				actaacaattcaagttttac
				aatcatagataatcaagata
				acacagctgtcattttgagt
				aatagaactggtttcaatct
				taaagaagagcctgtcttct
				acatgatcatcttgattgct
				gataacgggatcccatctct
				cacaagcacaaacactctca
				ctatccaagtctgtgactgt
				ggagacagtagaaacacaga
				aacttgtgctaacaagggac
				ttctctttatcatgggattc
				agaacagaggcaataattgc
				catcatgatatgtgttatgg
				taatatttgggtttttcttt
				ttgattcttgctctgaaaca
				gcgaagaaaggagactctat
				ttccagagaagactgaagac
				tttagggagaatatattttg
				ctatgatgatgaaggcggcg
				gggaagaagatacagaggcc
				tttgatatagcagagctgag
				gagtagtaccataatgcggg
				aacgcaagactcggaaaacc
				acaagcgcggagatcaggag
				cttgtacaggcagtccctgc
				aggtgggcccagacagtgcc
				atatttcgaaaatttatcct
				agagaagcttgaagaagcca
				acacagacccatgtgctccc
				ccctttgattcactacagac
				gtttgcctatgagggaacag
				ggtcatcagctggctctctg
				agctccttagaatcagcagt
				ctctgatcaggatgaaagct
				atgattaccttaatgagttg
				ggacctcgctttaaaagatt
				agcatgcatgtttggctctg
				cagtacaacccaacaattag

962	C137917	artifi-	aa	AWVWRPFvvLEEMDDIQCVG
	muCDH19	cial		KLRSDLDNGNNSFQYKLLGI
	(44-362)			GAGSFSINERTGEICAIQKL
	huCDH19			DREEKSLYILRAQVIDTTIG
	(365-772)			KAVETESEFVIRVLDINDNE
				PRFLDEPYEAIVPEMSPEGT
				FVIKVTANDADDPSTGYHAR
				ILYNLERGQPYFSVEPTTGV
				IRISSKMDRELQDTYCVIIQ
				AKDMLGQPGALSGTTTVSIK
				LSDINDNKPIFKESFYRFTI
				SESAPIGTSIGKIMAYDDDI
				GENAEMEYSIEDDDSKIFDI
				IIDNDTQEGIVILKKKVDFE
				QQSYYGIRAKVKNCHVDEEL
				APAHVNASTTYIKVQVEDED
				EPPLFLLPYYVFEVFEETPQ
				GSFVGvvSATDPDNRKSPIR
				YSITRSKVFNINDNGTITTS
				NSLDREISAWYNLSITATEK
				YNIEQISSIPLYVQVLNIND
				HAPEFSQYYETYVCENAGSG
				QVIQTISAVDRDESIEEHHF
				YFNLSVEDTNNSSFTIIDNQ
				DNTAVILTNRTGFNLQEEPV
				FYISILIADNGIPSLTSTNT
				LTIHVCDCGDSGSTQTCQYQ
				ELVLSMGFKTEVIIAILICI
				MIIFGFIFLTLGLKQRRKQI
				LFPEKSEDFRENIFQYDDEG
				GGEEDTEAFDIAELRSSTIM
				RERKTRKTTSAEIRSLYRQS
				LQVGPDSAIFRKFILEKLEE
				ANTDPCAPPFDSLQTYAFEG
				TGSLAGSLSSLESAVSDQDE
				SYDYLNELGPRFKRLACMFG
				SAVQSNN

963	C137917	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgtcgttctagaagaaatgg
	(44-362)			atgatatacaatgtgttgga
	huCDH19			aagctaagatctgacttaga
	(365-772)			caatggaaacaactctttcc
				agtacaagctactggggatt
				ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatacagaagctt
				gatagagaggaaaaatccct
				ctacattctgagagcccagg
				taatagacaccactattggg
				aaggctgtggaaactgaatc
				cgagtttgtcatcagagttt
				tggatatcaatgacaatgaa
				cccagattcctagatgaacc
				atatgaggccattgtacctg
				agatgtctccagaaggaaca
				tttgtcatcaaggtgacagc
				caatgacgcagatgatcctt
				caactggctatcatgctcgc
				atcctataca
				acttagaacgaggtcaacca
				tacttttctgttgagccaac
				aacaggagtcataaggatat
				cttctaagatggatagagag
				ttgcaagatacatactgtgt
				aattattcaagccaaggaca
				tgctcggtcagcctggagcc
				ttgtctggaacaacaaccgt
				atcaattaagctgtcagata
				ttaatgacaacaagccaata
				ttcaaagaaagtttctaccg
				cttcactatatctgaatctg
				cacccattggaacatcaata
				gggaaaattatggcatatga
				tgatgacataggggagaatg
				cagagatggagtacagcatt
				gaagatgatgattcaaaaat
				atttgacataatcattgaca
				atgacacccaagaagggata
				gttatacttaaaaagaaagt
				tgattttgagcagcagagct
				attatggcattagagctaag
				gttaaaaactgccatgtgga
				tgaagagcttgcacctgccc
				atgttaacgcttccacaacc
				tacattaaagttcaagtaga
				agatgaagatgagcctcctc
				ttttcctccttccatattat
				gtatttgaagtttttgaaga
				aaccccacagggaLcatttg
				taggcgtggtgtctgccaca
				gacccagacaataggaaatc
				tcctatcaggtattctatta
				ctaggagcaaagtgttcaat
				atcaatgataatggtacaat
				cactacaagtaactcactgg
				atcgtgaaatcagtgct~gg
				tacaacctaagtattacagc
				cacagaaaaatacaatatag
				aacagatctcttcgatccca
				ctgtatgtgcaagttcttaa
				catcaatgatcatgctcctg
				agttctctcaatactatgag
				acttatgtttgtgaaaatgc
				aggctctggtcaggtaattc
				agactatcagtgcagtggat
				agagatgaatccatagaaga
				gcaccatttttactttaatc
				tatctgtagaagacactaac
				aattcaagttttacaatcat
				agataatcaagataacacag
				ctgtcattttgactaataga
				actggttttaaccttcaaga
				agaacctgtcttctacatct
				ccattcttaattgccgacaat
				ggaatcccgtcacttacaag
				tacaaacacccttaccatcc
				atgtctgtgactgtggtgac
				agtgggagcacacagacctg
				ccagtaccaggagcttgtgc
				tttccatgggattcaagaca
				gaagtcatcattgctattct
				catttgcattatgatcatat
				ttgggtttatttttttgact
				ttgggtttaaaacaacggag
				aaaacagattctatttcctg
				agaaaagtgaagatttcaga
				gagaatatattccaatatga
				tgatgaagggggtggagaag
				aagatacagaggcctttgat
				atagcagagctgaggagtag
				taccataatgcgggaacgca
				agactcggaaaaccacaagc
				gctgagatcaggagcctata
				caggcagtctttgcaagttg
				gccccgacagtgccatattc
				aggaaattcattctggaaaa
				gctcgaagaagctaatactg
				atccgtgtgcccctcctttt
				gattccctccagacctacgc
				ttttgagggaacagggtcat
				tagctggatccctgagctcc
				ttagaatcagcagtctctga
				tcaggatgaaagctatgatt
				accttaatgagttgggacct
				cgctttaaaagattagcatg
				catgtttggttctgcagtgc
				agtcaaataattag

964	C137915	artifi-	aa	AWVWRPFWLEEMDDIQCVGK
	muCDH19	cial		LRSDLDNGNNSFQYKLLGIG
	(44-461)			AGSFSINERTGEICAIQKLD
	huCDH19			REEKSLYILRAQVIDTTIGK
	(464-772)			AVETESEFVIRVLDINDNEP
				RFLDSPYEAIVPEMSPEGTF
				VIKVTANDADDPSTGYHARI
				LYNLERGQPYFSVEPTTGVI
				RISSKMDRELQDTYCVIIQA
				KDMLGQPGALSGTTTVSIKL
				SDINDNKPIFKESFYRFTIS
				ESAPIGTSIGKIMAYDDDIG
				ENAEMEYSIEDDDSKIFDil
				iDNDTQEGIVILKKKVDFSQ
				QSYYGIRAKVKNCHVDEELA
				PAHVNASTTYIKVQVEDEDE
				PPVFLLPYYILEIPEGKPYG
				TIVGTVSATDPDRRQSPMRY
				YLTGSKMFDINDN3TIITTN
				MLDREVSAWYNLTVTATETY
				NVQQISSAHVYVQVFNINDH
				APEFSQYYETYVCENAGSGQ
				VIQTISAVDRDESIEEHHFY
				FNLSVEDTNNSSFTIIDNQD
				NTAVILTNRTGFNLQEEPVF
				YISILIADNGIPSLTSTNTL
				TIHVCDCGDSGSTQTCQYQE
				LVLSMGFKTEVIIAILICIM
				IIFGFIFLTLGLKQRRKQIL
				FPEKSEDFRENIFQYDDEGG
				GEEDTEAFDIAELRSSTIMR
				ERKTRKTTSAEIRSLYRQSL
				QVGPDSAIFRKFILEKLEEA
				NTDPCAPPFDSLQTYAFEGT
				GSLAGSLSSLESAVSDQDES
				YDYLNELGPRFKRLACMFGS
				AVQSNN

965	C137915	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgttgttctagaagaaatgg
	(44-461)			atgatatacaatgtgttgga
	huCDH19			aagctaagatctgacttaga
	(464-772)			caatggaaacaactctttcc
				agtacaagctactggggatt
				ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatacagaagctt
				gatagagaggaaaaatccct
				ctacattctgagagcccagg
				taatagacaccactattggg
				aaggctgtggaaactgaatc
				cgagtttgtcatcagagttt
				tggatatcaatgacaatgaa
				cccagattcctagatgaacc
				atatgaggccattgtacctg
				agatgtctccagaaggaaca
				tttgtcatcaaggtgacagc
				caatgacgcagatgatcctt
				caactggctatcatgctcgc
				atcctatacaacttagaacg
				aggtcaaccatacttttctg
				ttgagccaacaacaggagtc
				ataaggatatcttctaagat
				ggatagagagttgcaa
				gatacatactgtgtaattat
				tcaagccaaggacatgctcg
				gtcagcctggagccttgtct
				ggaacaacaaccgtatcaat
				taagctgtcagatattaatg
				acaacaagccaatattcaaa
				gaaagtttctaccgcttcac
				tatatctgaatctgcaccca
				ttggaacatcaatagggaaa
				attatggcatatgatgatga
				cataggggagaatgcagaga
				tggactacagcattgaagat
				gatgattcaaaaatatttga
				cataatcattgacaatgaca
				cccaagaagggatagttata
				cttaaaaagaaagttgattt
				tgagcagcagagctattatg
				gcattagagctaaggttaaa
				aactgccatgtggatgaaga
				gcttgcacctgcccatgtta
				acgcttccacaacctacatt
				aaagttcaagtagaagatga
				agatgaacctcctgttttcc
				tcttaccatattacatactt
				gaaattcctgaaggaaaacc
				atatggaacaattgtgggga
				cggtttctgccacagaccca
				gatcgaagacaatctcctat
				gagatattatctcactggaa
				gcaaaatgtttgaLatcaat
				gacaatggaacaataatcac
				cactaacatgcttgacagag
				aggtcagtgcttggtacaac
				ttgactgtcacagctactga
				aacatacaatgtacaacaga
				tctcttcagcccatgtttat
				gtacaagtctttaacattaa
				tgatcatgctcctgagttct
				ctcaatactatgagacttat
				gtttgtgaaaatgcaggctc
				tggtcaggtaattcagacta
				tcagtgcagtggatagagat
				gaatccatagaacagcacca
				tttttactttaatctatctg
				tagaagacactaacaattca
				agttttacaatcatagataa
				tcaagataacacagctgtca
				ttttgactaatagaactggt
				tttaaccttcaagaagaacc
				tgtcttctacatctccatct
				taattgccgacaatggaatc
				ccgtcacttacaagtacaaa
				cacccttaccatccaLgtct
				gtgactgtggtgacagtggg
				agcacacagacctgccagta
				ccaggagctttgtgctttcca
				tgggattcaagacagaagtc
				atcattgctattctcatttg
				cattatgatcatatttgggt
				ttatttttttgactttgggt
				ttaaaacaacggagaaaaca
				gattctatttcctgagaaaa
				gtgaagatttcagagagaat
				atattccaatatgatgatga
				agggcgtggagaagaagata
				cagaggcctttgatatagca
				gagctgaggagtagtaccat
				aatgcgggaacgcaagactc
				ggaaaaccacaagcgctgag
				atcaggagcctatacaggca
				gtctttgcaagttggccccg
				acagtgccatattcaggaaa
				ttcattctggaaaagctcga
				agaagctaatactgatccgt
				gtgcccctccttttgattcc
				ctccagacctacgcttttga
				gggaacagggtcattagctg
				catccctgagctccttagaa
				tcagcagtctctgatcagga
				tgaaagctatgattacctta
				atgagttgggacctcgcttt
				aaaagattagcatgcatgtt
				tggttctgcagtgcagtcaa
				ataattag

966	C71144	artifi-	aa	AWVWRPFVVLEEMDDIQCVG
	muCDH19	cial		KLRSDLDNGNNSFQYKLLGI
	(44-770)			GAGSFSINERTGEICAIQKL
				DREEKSLYILRAQVIDTTIG
				KAVETESEFVIRVLDINDNE
				PRFLDEPYEAIVPEMSPEGT
				FVIKVTANDADDPSTGYHAR
				ILYNLERGQPYFSVEPTTGV
				IRISSKMDRELQDTYCVIIQ
				AKDMLGQPGALSGTTTVSIK
				LSDINDNKPIFKESFYRFTI
				SESAPIGTSIGKIMAYDDDI
				GENAEMEYSIEDDDSKIFDI
				IIDNDTQEGIVILKKKVDFE
				QQSYYGIRAKVKNCHVDEEL
				APAHVNASTTYIKVQVEDED
				EPPVFLLPYYILEIPEGKPY
				GTIVGTVSATDPDRRQSPMR
				YYLTGSKMFDINDNSTIITT
				NMLDREVSAWYNLTVTATET
				YNVQQISSAHVYVQVFNIND
				NAPEFSQFYETYVCENAESG
				EIVQIISAIDRDESIEDHHF
				YFNHSLEDTNNSSFMLTDNQ
				DNTAVILSNRTGFNLKEEPV
				FYMIILIADNGIPSLTSTNT
				LTIQVCDCGDSRNTETCANK
				GLLFIMGFRTEAIIAIMICV
				MVIFGFFFLILALKQRRKET
				LFPEKTEDFRENIFCYDDEG
				GGEEDSEAFDIVELRQSTVM
				RERKPQRSKSAEIRSLYRQS
				LQVGPDSAIFRKFILEKLEE
				ANTDPCAPPFDSLQTFAYEG
				TGSSAGSLSSLASRDTDQED
				DFDYLNDLGPRFKRLASMFG
				SAVQPNN

967	C71144	artifi-	nt	gcctgggtgtggagaccatt
	muCDH19	cial		tgttgttctagaagaaatgg
	(44-770)			atgatatacaatgtgttgga
				aagctaagatctgacttaga
				caatggaaacaactctttcc
				agtacaagctactggggatt
				ggcgctggaagctttagcat
				taatgaaagaacaggtgaaa
				tatgtgccatacagaagctt
				gatagagaggaaaaatccct
				ctacattctgagagcccagg
				taatagacaccactattggg
				aaggctgcggaaactgaatc
				cgagtttgtcatcagagttt
				tggatatcaatgacaatgaa
				cccagattcctagatgaacc
				atatgaggccattgtacctg
				agatgtctccagaaggaaca
				tttgtcatcaaggtgacagc
				caatgacgcagatgatcctt
				caactggctatcatgctcgc
				atcctatacaacttagaacg
				aggtcaaccatacttttctg
				ttgagccaacaacaggagtc
				ataaggatatcttctaagat
				ggatagagagttgcaagata
				catactgtgtaattattcaa
				gccaaggacatgctcggtca
				gcctggagccttgtctggaa
				caacaaccgtatcaattaag
				ctgtcagatattaatgacaa
				caagccaatattcaaagaaa
				gtttctaccgcttcactata
				tctgaatctgcacccattgg
				aacatcaatagggaaaatta
				tggcatatgatgatgacata
				ggggagaatgcagagatgga
				gtacagcattgaagatgatg
				attcaaaaatatttgacata
				atcattgacaatgacaccca
				agaagggatagttatactta
				aaaagaaagttgattttgag
				cagcagagccaitatggcat
				tagagctaaggttaaaaact
				gccatgtggatgaagagctt
				gcacctgcccatgttaacgc
				ttccacaacctacattaaag
				ttcaagtagaagatgaagat
				gaacctcctgttttcctctt
				accatattacatacttgaaa
				ttcctgaaggaaaaccatat
				ggaacaattgtggggacggt
				ttctgccacagacccagatc
				gaagacaatctcctatgaga
				tattatctcactggaagcaa
				aatgtttgatatcaatgaca
				atggaacaataatcaccact
				aacatgcttgacagagaggt
				cagtgcttggtacaacttga
				ctgtcacagctacLgaaaca
				tacaatgtacaacagatctc
				ttcagcccatgtttatgtac
				aagtctttaacattaacgac
				aatgctccagagttctctca
				attctatgagacttatgttt
				gtgaaaatgctgaatctggt
				gagatagttcagatcatcag
				tgcaattgatagagatgagt
				ccatagaagatcaccatttt
				tactttaatcactctctgga
				agacacaaacaactcaagtt
				ttatgctaacagacaatcaa
				gataacacagctgtaattct
				gagtaatagaactggtttca
				atcttaaagaagagcctgtc
				ttctacatgatcatcttgat
				tgctgataacgggatcccat
				ctctcacaagcacaaacact
				ctcactatccaagtctgtga
				ctgtggagacagtagaaaca
				cagaaacttgtgctaacaag
				ggacttctctttatcatggg
				attcagaacagaggcaataa
				ttgccatcatgatatgtgtt
				atggtaatatttgggttttt
				ctttttgatttctttgctctg
				aaacagcgaagaaaggagact
				ctatttccagagaagactga
				agactttagggagaatatat
				tttgctatgatgatgaaggc
				ggcggggaagaagactcgga
				agcctttgacatcgtagagc
				tgagacaaagtacagtaatg
				agagaaagaaagcctcagag
				aagcaagagtgcggagatca
				ggagcttgtacaggcagtcc
				ctgcaggtgggcccagacag
				tgccatatttcgaaaattta
				tcctagagaagcttgaagaa
				gccaacacagacccatgtgc
				tcccccctttgattcactac
				agacgtttgcctatgaggga
				acagggtcatcagctggctc
				tctgagctccttggcatcca
				gagacaccgatcaggaggat
				gacttcgactaccttaatga
				cctgggacctcgttttaaaa
				gattagcaagcatgtttggc
				tctgcagtacaacccaacaa
				ttag

968	Flag Tag	artifi-	aa	DYKDDDDK
		cial

969	Flag Tag	artifi-	nt	gactacaaagacgatgacga
		cial		caag

970	ckCDH19	artifi-	aa	MNCSTFLSLVLALVQLQLCS
	(1-43)::	cial		PTTQIFSAQKTDQSYTTIRR
	FLAG::ckC			VKRDYKDDDDKGWVWEPLFV
	DH19			TEEETSTMPMYVGQLKSDLD
	(44-776)			KEDGSLQYILTGEGADSIFF
				INEHGKIYVRQKLDREKKSF
				YILRAQVINRKTRHPIEPDS
				EFIIKVRDINDHEPQFLDGP
				YVATVPEMSPEGTSVTQVTA
				TDGDDPSYGNNARLLYSLIQ
				GQPYFSVEPKTGVIRMTSQM
				DRETKDQYLVVIQAKDMVGQ
				AGAFSATATVTINLSDVNDN
				PPKFQQRLYYLNVSEEAPVG
				TTVGRLLAEDSDIGENAAMN
				YFIEEDSSDVFGIITDRETQ
				EGIIILKKRVDYESKRKHSV
				RVKAVNRYIDDRFLKEGPFE
				DITIVQISVVDADEPPVFTL
				ESYVMEIAEGVVSGSLVGTV
				SARDLDNDDSSVRYSIVQGL
				HLKRLFSINEHNGTIITTEP
				LDREKASWHNITVTATETRN
				PEKISEANVYIQVLDVNDHA
				PEFSKYYETFVCENAVPGQL
				IQNISAVDKDDSAENHRFYF
				SLAQATNSSHFTVKDNQDNT
				AGIFTA3SGFSRKEQFYFFL
				PILILDNGSPPLTSTNTLTV
				TVCDCDTEVNTLYCRYGAFL
				YSIGLSTEALVAVLACLLIL
				LVFFLAIIGIRQQRKKTLFS
				EKVEEFRENIVRYDDEGGGE
				EDTEAFDISALRTRAVLRTH
				KPRKKITTEIHSLYRQSLQV
				GPDSAIFRQFISEKLEEANT
				DPSVPPYDSLQTYAFEGTGS
				LAGSLSSLGSNTSDVDQNYE
				YLVGWGPPFKQLAGMYTSQR
				STRD

971	huCDH19(1-			MNCYLLLRFMLGIPLLWPCL
	43)::FLAG::			GATENSQTKKVKQPVRSHLR
	hu(44-			VKRDYKDDDDKGWVWNQFFV
	141)::			PEEMNTTSHHIGQLRSDLDN
	ckCDH1			GNNSFQYKLLGAGAGSTFII
	9(142-776)			DERTGDIYAIQKLDREERSL
				YILRAQVIDIATGRAVEPES
				EFVIKVSDINDHEPQFLDGP
				YVATVPEMSPEGTSVTQVTA
				TDGDDPSYGKNARLLYSLIQ
				GQPYFSVEPKTGVIRKTSQM
				DRETKDQYLVVIQAKDMVGQ
				AGAFSATATVTIKLSDVNDN
				PPKFQQRLYYLNVSEEAPVG
				TTVGRLLAEDSDIGENAAMN
				YFIEEDSSDVFGIITDRETQ
				EGIIILKKRVDYESKRKHSV
				RVKAVNRYIDDRFLKEGPFE
				DITIVQISVVDADEPPVFTL
				ESYVMEIAEGVVSGSLVGTV
				SARDLDNDDSSVRYSIVQGL
				HLKRLFSINE
				HNGTIITTEPLDREKASWHN
				ITVTATETRNPEKISEANVY
				IQVLDVNDHAPEFSKYYETF
				VCENAVPGQLIQNISAVDKD
				DSAENHRFYFSLAQATNSSH
				FTVKDNQDNTAGIFTAGSGF
				SRKEQFYFFLPILILDNGSP
				PLTSTNTLTVTVCDCDTEVN
				TLYCRYGAFLYSIGLSTEAL
				VAVLACLLILLVFFLAIIGI
				RQQRKKTLFSEKVEEFRENI
				VRYDDEGGGEEDTEAFDISA
				LRTRAVLRTHKPRKKITTEI
				HSLYRQSLQVGPDSAIFRQF
				ISEKLEEANTDPSVPPYDSL
				QTYAFEGTGSLAGSLSSLGS
				NTSDVDQNYEYLVGWGPPFK
				QLAGMYTSQRSTRD

972	ckCDH19(1-			MNCSTFLSLVLALVQLQLCS
	43)::			PTTQIFSAQKTDQSYTTIRR
	FLAG::ckC			VKRDYKDDDDKGWVWEPLFV
	DH19(44-			TEEETSTMPMYVGQLKSDLD
	141)::			KEDGSLQYILTGEGADSIFF
	huCDH1			INEHGKIYVRQKLDREKKSF
	9(142-			YILRAQVINRKTRHPIEPDS
	249)::			EFIIKVRDINDNEPKFLDEP
	ckCDH1			YEAIVPEMSPEGTLVIQVTA
	9(250-776)			SDADDPSSGNNARLLYSLLQ
				GQPYFSVEPTTGVIRISSKM
				DRELQDEYWVIIQAKDMIGQ
				PGALSGTTSVLIKLSDVNDN
				PPKFQQRLYYLNVSEEAPVG
				TTVGRLLAEDSDIGENAAMN
				YFIEEDSSDVFGIITDRETQ
				EGIIILKKRVDYESKRKHSV
				RVKAVNRYIDDRFLKEGPFE
				DITIVQISVVDADEPPVFTL
				ESYVMEIAEGVVSGSLVGTV
				SARDLDNDDSSVRYSIVQGL
				HLKRLFSINEHNGTIITTEP
				LDREKASWHNITVTATETRN
				PEKISEANVYIQVLDVNDHA
				PEFSKYYETFVCENAVPGQL
				IQNISAVDKDDSAENHRFYF
				SLAQATNSSHFTVKDNQDNT
				AGIFTAGSGFSRKEQFYFFL
				PILILDNGSPPLTSTNTLTV
				TVCDCDTEVNTLYCRYGAFL
				YSIGLSTEALVAVLACLLIL
				LVFFLAIIGIRQQRKKTLFS
				EKVEEFRENIVRYDDEGGGE
				EDTEAFDISALRTRAVLRTH
				KPRKKITTEIHSLYRQSLQV
				GPDSAIFRQFISEKLEEANT
				DPSVPPYDSLQTYAFEGTGS
				LAGSLSSLGSNTSDVDQNYE
				YLVGWGPPFKQLAGMYTSQR
				STRD

973	ckCDH19(1-			MNCSTFLSLVLALVQLQLCS
	43)::			PTTQIFSAQKTDQSYTTIRR
	FLAG::ckC			VKRDYKDDDDKGWVWEPLFV
	DH19(44-			TEEETSTMPMYVGQLKSDLD
	249)::			KEDGSLQYILTGEGADSIFF
	huCDH1			INEHGKIYVRQKLDREKKSF
	9(250-			YILRAQVINRKTRHPIEPDS
	364)::			EFIIKVRDINDHEPQFLDGP
	ckCDH1			YVATVPEMSPEGTSVTQVTA
	9(365-776)			TDGDDPSYGKNARLLYSLIQ
				GQPYFSVEPKTGVIRKTSQM
				DRETKDQYLWIQAKDMVGQA
				GAFSATATVTINLSDVNDNK
				PIFKESLYRLTVSESAPTGT
				SIGTIMAYDNDIGENAEMDY
				SIEEDDSQTFDIITNHETQE
				GIVILKKKVDFEHQNHYGIR
				AKVKNHHVPEQLMKYHTEAS
				TTFIKIQVEDVDEPPVFTLE
				SYVMEIAEGWSGSLVGTVSA
				RDLDNDDSSVRYSIVQGLHL
				KRLFSINEHNGTIITTEPLD
				REKASWHNITVTATETRNPE
				KISEANVYIQVLDVNDHAPE
				FSKYYETFVCENAVPGQLIQ
				NISAVDKDDSAENHRFYFSL
				AQATNSSHFTVKDNQDNTAG
				IFTAGSGFSRKEQFYFFLPI
				LILDNGSPPLTSTNTLTVTV
				CDCDTEVNTLYCRYGAFLYS
				IGLSTEALVAVLACLLILLV
				FFLAIIGIRQQRKKTLFSEK
				VEEFRENIVRYDDEGGGEED
				TEAFDISALRTRAVLRTHKP
				RKKITTEIHSLYRQSLQVGP
				DSAIFRQFISEKLEEANTDP
				SVPPYDSLQTYAFEGTGSLA
				GSLSSLGSNTSDVDQNYEYL
				VGWGPPFKQLAGMYTSQRST
				RD

974	ckCDH19(1-			MNCSTFLSLVLALVQLQLCS
	43)::			PTTQIFSAQKTDQSYTTIRR
	FLAG::ckC			VKRDYKDDDDKGWVWEPLFV
	DH19(44-			TEEETSTMPMYVGQLKSDLD
	364)::			KEDGSLQYILTGEGADSIFF
	huCDH1			INEHGKIYVRQKLDREKKSF
	9(365-			YILRAQVINRKTRHPIEPDS
	463)::			EFIIKVRDINDHEPQFLDGP
	ckCDH1			YVATVPEMSPEGTSVTQVTA
	9(469-776)			TDGDDPSYGNNARLLYSLIQ
				GQPYFSVEPKTGVIRMTSQM
				DRETKDQYLVVIQAKDMVGQ
				AGAFSATATVTINLSDVNDN
				PPKFQQRLYYLNVSEEAPVG
				TTVGRLLAEDSDIGENAAMN
				YFIEEDSSDVFGIITDRETQ
				EGIIILKKRVDYESKRKHSV
				RVKAVNRYIDDRFLKEGPFE
				DITIVQISVVDADEPPLFLL
				PYYVFEVFEETPQGSFVGVV
				SATDPDNRKSPIRYSITRSK
				VFNINDNGTITTSNSLDREI
				SAWYNLSITATEKYNIEQIS
				SIPLYVQVLNINDHAPEFSK
				YYETFVCENAVPGQLIQNIS
				AVDKDDSAENHRFYFSLAQA
				TNSSHFTVKDNQDNTAGIFT
				AGSGFSRKEQFYFFLPILIL
				DNGSPPLTSTNTLTVTVCDC
				DTEVNTLYCRYGAFLYSIGL
				STEALVAVLACLLILLVFFL
				AIIGIRQQRKKTLFSEKVEE
				FRENIVRYDDEGGGEEDTEA
				FDISALRTRAVLRTHKPRKK
				ITTEIHSLYRQSLQVGPDSA
				IFRQFISEKLEEANTDPSVP
				PYDSLQTYAFEGTGSLAGSL
				SSLGSNTSDVDQNYEYLVGW
				GPPFKQLAGMYTSQRSTRD

975	(1-			MNCSTFLSLVLALVQLQLCS
	43)::			PTTQIFSAQKTDQSYTTIRR
	FLAG::ckC			VKRDYKDDDDKGWVWEPLFV
	DH19(44-			TEEETSTMPMYVGQLKSDLD
	468)::			KEDGSL
	huCDH1			QYILTGEGADSIFFIKEHGK
	9(464-772)			IYVRQKLDREKKSFYILRAQ
				VINRKTRHPIEPDSEFIIKV
				RDINDHEPQFLEGPYVATVP
				EMSPEGTSVTQVTATDGDDP
				SYGNNARLLYSLIQGQPYFS
				VEPKTGVIRMTSQMDRETKD
				QYLVVIQAKDMVGQAGAFSA
				TATVTINLSDVNDNPPKFQQ
				RLYYLNVSEEAPVGTTVGRL
				LAEDSDIGENAAMNYFIEED
				SSDVFGIITDRETQEGIIIL
				KKRVDYESKRKHSVRVKAVN
				RYIDDRFLKEGPFEDITIVQ
				ISVVDADEPPVFTLESYVME
				IAEGVVSGSLVGTVSARDLD
				MDDSSVRYSIVQGLHLKRLF
				SINEHNGTIITTEPLDREKA
				SWHNITVTATETRNPEKISE
				ANVYIQVLDVNDHAPEFSQY
				YETYVCENAGSGQVIQTISA
				VDRDESIEEHHFYFNLSVED
				TNNSSFTIIDNQDNTAVILT
				NRTGFNLQEEPVFYISILIA
				DNGIPSLTSTNTLTIHVCDC
				GDSGSTQTCQYQELVLSMGF
				KTEVIIAILICIMIIFGFIF
				LTLGLKQRRKQILFPEKSED
				FRENIFQYDDEGGGEEDTEA
				FDIAELRSSTIMRERKTRKT
				TSAEIRSLYRQSLQVGPDSA
				IFRKFILEKLEEANTDPCAP
				PFDSLQTYAFEGTGSLAGSL
				SSLESAVSDQDESYDYLNEL
				GPRFKRLACMFGSAVQSNN

976	rhCDH19(1-			MNCYLLLPFMLGIPLLKPCL
	43)::			GATENSQTKKVQQPVGSHLR
	FLAG::rhC			VKRDYKDDDDKGWVWNQFFV
	DH19			PEEMNTTSHHVGRLRSDIDN
	(44-772)			GNNSFQYKLLGAGAGSTFII
				DERTGDIYAIEKLDREERSL
				YILRAQVIDITTGRAVEPES
				EFVIKVSDINDNEPKFLDEP
				YEAIVPEMSPEGTLVIQVTA
				SDADDPSSGNNARLLYSLLQ
				GQPYFSVEPTTGVIRISSKM
				DRELQDEYWVIIQAKDMIGQ
				PGALSGTTSVLIKLSDVNDN
				KPIFKESLYRLTVSESAPTG
				TSIGTIMAYDNDIGENAEMD
				YSIEEDDSQTFDIITNHETQ
				EGIVILKKKVNFEHQNHYGI
				RAKVKNHHVDEQLMKYHTEA
				STTFIKIQVEDVDEPPLFLL
				PYYIFEIFEETPQGSFVGVV
				SATDPDNRKSPIRYSITRSK
				VFNIDDNGTITTTNSLDREI
				SAWYNLSITATEKYNIEQIS
				SIPVYVQVLNINDHAPEFSQ
				YYESYVCENAGSGQVIQTIS
				AVDRDESIEEHHFYFNLSVE
				DTNSSSFTIIDNQDNTAVIL
				TNRTGFNLQEEPIFYISILI
				ADNGIPSLTSTNTLTIHVCD
				CDDSGSTQTCQYQELMLSMG
				FKTEVIIAILICIMVIFGFI
				FLTLGLKQRRKQILFPEKSE
				DFRENIFRYDDEGGGEEDTE
				AFDVAALRSSTIMRERKTRK
				TTSAEIRSLYRQSLQVGPDS
				AIFRKFILEKLEEADTDPCA
				PPFDSLQTYAFEGTGSLAGS
				LSSLESAVSDQDESYDYLNE
				LGPRFKRLACMFGSAVQSNM

977	caCDH19(1-			QFFVPEEMNKTDYHIGQLRS
	42)::			DLDNGNNSFQYKLLGAGAGS
	FLAG::caC			IFVIDERTGDIYAIQKLDRE
	DH19			ERSLYTLRAQVIDSTTGRAV
	(43-770)			EPESEFVIRVSDINDNEPKF
				LDEPYEAIVPEMSPEGTLVI
				QVTATDADDPASGNNARLLY
				SLLQGQPYFSIEPTTGVIRI
				SSKMDRELQDEYWVIIQAKD
				MIGLPGALSGTTSVLIKLSD
				VNDNKPIFKERLYRLTVSES
				APTGTSIGRIMAYDNDIGEN
				AEMDYSIEDDSQTFDIITNN
				ETQEGIVILKKKVDFEHQNH
				YLIRANVKNRHVAEHLMEYH
				VEASTTFVRVQVEDEDEPPV
				FLLPYYLFEILEESPHGSFV
				GMVSATDPDQRKSPIRYSIT
				RSKVFSIDDNGTIITTNPLD
				REISAWYNLSITATEKYNVQ
				QISAVPVYVQVLNINDHAPE
				FSEYYDSYVCENAGSGQVIQ
				TISAVDRDESVEDHHFYFNL
				SVEDTKNSSFIIIDNEDNTA
				VILTNRTGFSLQEEPVFYIS
				VLIADNGIPSLTSTNTLTIH
				ICDCDDYGSTQTCRDKDLLL
				SMGFRTEVILAILISIMIIF
				GFIFLILGLKQRRKPTLFPE
				KGEDFRENIFRYDDEGGGEE
				DTEAFDIVQLRSSTIMRERK
				TRKTAAAEIRSLYRQSLQVG
				PDSAIFRKFILEKLEEANTD
				PCAPPFDSLQTYAFEGTGSL
				AGSLSSLGSAVSDQDENYDY
				LNELGPRFKRLACMFGSAMQ
				SNN

978	rhCDH19(1-			MNCYLLLPFMLGIPLLWPCL
	43):			GATENSQTKKVQQPVGSHLR
	FLAG::rhC			VKRDYKDDDDKGWVWNQFFV
	DH19(44-			PEEMNTTSHHVGRLRSDLDN
	141)::			GNNSFQYKLLGAGAGSTFII
	caCDH1			DERTGDIYAIEKLDREERSL
	9(141-770)			YILRAQVIDITTGRAVEPES
				EFVIKVSDINDNEPKFLDEP
				YEAIVPEMSPEGTLVIQVTA
				TDADDPASGNNARLLYSLLQ
				GQPYFSIEPTTGVIRISSKM
				DRELQDEYKVIIQAKDMIGL
				PGALSGTTSVLIKLSDVNDN
				KPIFKERLYRITVSESAPTG
				TSIGRIMAYDNDIGENAEMD
				YSIEDDSQTFDIITNNETQE
				GIVILKKKVDFEHQNHYLIR
				ANVKNRHVAEHLMEYHVEAS
				TTFVRVQVEDEDEPPVFLLP
				YYLFEILEESPHGSFVGMVS
				ATDPDQRKSPIRYSITRSKV
				FSIDDNGTIITTNPLDREIS
				AWYNLSITATEKYNVQQISA
				VPVYVQVLNINDHAPEFSEY
				YDSYVCENAGSGQVIQTISA
				VDRDESVEDHHFYFNLSVED
				TKNSSFIIIDNEDNTAVILT
				NRTGFSLQEEPVFYISVLIA
				DNGIPSLTSTNTLTIHICDC
				DDYGSTQTCRDKDLLLSMGF
				RTEVILAILISIMIIFGFIF
				LILGLKQRRKPTLFPEKGED
				FRENIFRYDDEGGGEEDTEA
				FDIVQLRSSTIMRERKTRKT
				AAAEIRSL
				YRQSLQVGPDSAIFRKFILE
				KLEEANTDPCAPPFDSLQTY
				AFEGTGSLAGSLSSLGSAVS
				DQDENYDYLNELGPRFKRLA
				CMFGSAMQSNN

979	rhCDH19(1-			MNCYLLLPFMLGIPLLWPCL
	43)::			GATENSQTKKVQQPVGSHLR
	FLAG::rhC			VKRDYKDDDOKGWVWNQFFV
	DH19(44-			PEEMNTTSHHVGRLRSDLDN
	65)::			GNNSFQYKLLGAGAGSIFVI
	caCDH19			DERTGDIYAIQKLDREERSL
	(65-770)			YTLRAQVIDSTTGRAVEPES
				EFVIRVSDINDNEPKFLDEP
				YEAIVPEMSPEGTLVIQVTA
				TDADDPASGNNARLLYSLLQ
				GQPYFSIEPTTGVIRISSKM
				DRELQDEYWVIIQAKDMIGL
				PGALSGTTSVLIKLSDVNDN
				KPIFKERLYRLTVSESAPTG
				TSIGRIMAYDNDIGENAEMD
				YSIEDDSQTFDIITNNETQE
				GIVILKKKVDFEHQNHYLIR
				ANVKNRHVAEHLMEYHVEAS
				TTFVRVQVEDEDEPPVFLLP
				YYLFEILEESPHGSFVGMVS
				ATDPDQRKSPIRYSITRSKV
				FSIDDNGTIITTNPLDREIS
				AWYNLSITATEKYNVQQISA
				VPVYVQVLNINDHAPEFSEY
				YDSYVCENAGSGQVIQTISA
				VDRDESVEDHKFYFNLSVED
				TKNSSFIIIDNEDNTAVILT
				NRTGFSLQEEPVFYISVLIA
				DNGIPSLTSTNTLTIHICDC
				DDYGSTQTCRDKDLLLSMGF
				RTEVILAILISIMIIFGFIF
				LILGLKQRRKPTLFPEKGED
				FRENIFRYDDEGGGEEDTEA
				FDIVQLRSSTIMRERKTRKT
				AAAEIRSLYRQSLQVGPDSA
				IFRKFILEKLEEANTDPCAP
				PFDSLQTYAFEGTGSLAGSL
				SSLGSAVSDQDENYDYLNEL
				GPRFKRLACMFGSAMQSNN

980	caCDH19(1-			MNYCFLLPLMLGIPLIWPCF
	43)::			TASESSKTEVKHQAGSHLRV
	FLAG::caC			KRDYKDDDDKGWMWNQFFVP
	DH19(44-			EEMNKTDYHIGQLRSDLDNG
	87)::			NNSFQYKLLGAGAGSTFIID
	rhCDH19(89-			ERTGDIYAIEKLDREERSLY
	114)::			ILRAQVIDSTTGRAVEPESE
	caCDH1			FVIRVSDINDNEPKFLDEPY
	9(115-770)			EAIVPEMSPEGTLVIQVTAT
				DADDPASGNNARLLYSLLQG
				QPYFSIEPTTGVIRISSKMD
				RELQDEYWVIIQAKDMIGLP
				GALSGTTSVLIKLSDVNDNK
				PIFKERLYRLTVSESAPTGT
				SIGRIMAYDNDIGENAEMDY
				SIEDDSQTFDIITNNETQEG
				IVILKKKVDFEHQNHYLIRA
				KVKNRHVAEHLMEYHVEAST
				TFVRVQVEDEDEPPVFLLPY
				YLFEILEESPHGSFVGMVSA
				TDPDQRKSPIRYSITRSKVF
				SIDDNGTIITTNPLDREISA
				WYNLSITATEKYNVQQISAV
				PVYVQVLNINDHAPEFSEYY
				DSYVCENAGSGQVIQTISAV
				DRDESVEDHHFYFNLSVEDT
				KNSSFIIIDNEDNTAVILTN
				RTGFSLQEEPVFYISVLIAD
				NGIPSLTSTNTLTIHICDCD
				DYGSTQTCRDKDLLLSMGFR
				TEVILAILISIMIIFGFIFL
				ILGLKQRRKPTLFPEKGEDF
				RENIFRYDDEGGGEEDTEAF
				DIVQLRSSTIMRERKTRKTA
				AAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDPCAPP
				FDSLQTYAFEGTGSLAGSLS
				SLGSAVSDQDENYDYLNELG
				PRFKRLACMFGSAMQSNN

981	caCDH19(1-			MNYCFLLPLMLGIPLIWPCF
	43)::			TASESSKTEVKHQAGSHLRV
	FLAG::caC			KRDYKDDDDKGWMWNQFFVP
	DH19(44-			EEMNKTDYHIGQLRSDLDNG
	120)::			NNSFQYKLLGAGAGSIFVID
	rhCDH1			ERTGDIYAIQKLDREERSLY
	9(122-			TLRAQVIDITTGRAVEPESE
	137)::			FVIKVSDINDNEPKFLDEPY
	caCDH1			EAIVPEMSPEGTLVIQVTAT
	9(137-770)			DADDPASGNNARLLYSLLQG
				QPYFSIEPTTGVIRISSKMD
				RELQDEYWVIIQAKDMIGLP
				GALSGTTSVLIKLSDVNDNK
				PIFKERLYRLTVSESAPTGT
				SIGRIMAYDNDIGENAEMDY
				SIEDDSQTFDIITNNETQEG
				IVILKKKVDFEHQNHYLIRA
				NVKNRHVAEHLMEYHVEAST
				TFVRVQVEDEDEPPVFLLPY
				YLFEILEESPHGSFVGMVSA
				TDPDQRKSPIRYSITRSKVF
				SIDDNGTIITTNPLDREISA
				WYNLSITATEKYNVQQISAV
				PVYVQVLNINDHAPEFSEYY
				DSYVCENAGSGQVIQTISAV
				DRDESVEDEHFYFNLSVEDT
				KNSSFIIIDNEDNTAVILTN
				RTGFSLQEEPVFYISVLIAD
				NGIPSLTSTNTLTIHICDCD
				DYGSTQTCRDKDLLLSMGFR
				TEVILAILISIMIIFGFIFL
				ILGLKQRRKPTLFPEKGEDF
				RENIFRYDDEGGGEEDTEAF
				DIVQLRSSTIMRERKTRKTA
				AAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDPCAPP
				FDSLQTYAFEGTGSLAGSLS
				SLGSAVSDQDENYDYLNELG
				PRFKRLACMFGSAMQSNN

982	rhCDH19(1-			MNCYLLLPFMLGIPLLWPCL
	43)::			GATENSQTKKVQQPVGSHLR
	FLAG::rhC			VKRDYKDDDDKGWVWNQFFV
	DH19(44-			PEEMNTTSHHVGRLRSDLDN
	141)::			GNNSFQYKLLGAGAGSTFII
	raCDH19			DERTGDIYAIEKLDREERSL
	(140-			YILRAQVIDITTGRAVEPES
	247)::			EFVIKVSDINDNEPRFLDEP
	rhCDH1			YEAIVPEMSPEGTFVIKVTA
	9(250-772)			NDADDPTSGYHARILYNLEQ
				GQPYFSVEPTTGVIRISSKM
				DRELQDTYCVIIQAKDMLGQ
				PGALSGTTTISIKLSDINDN
				KPIFKESLYRLTVSESAPTG
				TSIGTIMAYDNDIGENAEMD
				YSIEEDDSQTFDIITNHETQ
				EGIVILKKKVNFEHQNHYGI
				RAKV
				KNHHVDEQLMKYHTEASTTF
				IKIQVEDVDEPPLFLLPYYI
				FEIFEETPQGSFVGVVSATD
				PDNRKSPIRYSITRSKVFNI
				DDNGTITTTNSLDREISAWY
				NLSITATEKYNIEQISSIPV
				YVQVLNINDHAPEFSQYYES
				YVCENAGSGQVIQTISAVDR
				DESIEEKHFYFNLSVEDTNS
				SSFTIIDNQDNTAVILTNRT
				GFNLQEEPIFYISILIADNG
				IPSLTSTNTLTIHVCDCDDS
				GSTQTCQYQELMLSMGFKTE
				VIIAILICIMVIFGFIFLTL
				GLKQRRKQILFPEKSEDFRE
				NIFRYDDEGGGEEDTEAFDV
				AALRSSTIMRERKTRKTTSA
				EIRSLYRQSLQVGPDSAIFR
				KFILEKLEEADTDPCAPPFD
				SLQTYAFEGTGSLAGSLSSL
				ESAVSDQDESYDYLNELGPR
				FKRLACMFGSAVQSNN

983	raCDH19(1-			MNHYFLKYWILMVPLIWPCL
	43)::			KVAETLKIEKAQRAVPSLGR
	FLAG::raC			AKRDYKDDDDKGWVWKQFVV
	DH19			PEEMDTIQHVGRLRSDLDNG
	(44-770)			NNSFQYKLLGTGDGSFSIDE
				KTGDIFAMQKLDREKQSLYI
				LRAQVIDTTIGKAVEPESEF
				VIRVSDVNDNEPRFLDEPYE
				AIVPEMSPEGTFVIKVTAND
				ADDPTSGYHARILYNLEQGQ
				PYFSVEPTTGVIRISSKMDR
				ELQDTYCVIIQAKDMLGQPG
				ALSGTTTISIKLSDINDNKP
				IFKESFYRFTISESAPSGTT
				IGKIMAYDDDIGENAEMDYS
				IEDDESQIFDIVIDNETQEG
				IVILKKKVDFEHQNHYGIRV
				KVKNCHVDEELAPAHVNAST
				TYIKVQVEDEDEPPTFLLPY
				YIFEIPEGKPYGTMVGTVSA
				VDPDRRQSPMRYSLIGSKMF
				DINGNGTIVTTNLLDREVSA
				WYNLSVTATETYNVQQISSA
				HVYVQVLNINDHAPEFSQLY
				ETYVCENAESGEIIQTISAI
				DRDESIEDHHFYFNHSVEDT
				NNSSFILTDNQDNTAVILSN
				RAGFSLKEETVFYMIILIAD
				NGIPPLTSTNTLTIQVCDCG
				DSRSTETCTSKELLFIMGFK
				AEAIIAIVICVMVIFGFIFL
				ILALKQRRKETLFPEKTEDF
				RENIFCYDDEGGGEEDSEAF
				DIIELRQSTVMRERKPRKSR
				SAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDSSAPP
				FDSLQTFAYEGTGSSAGSLS
				SLGSSVTDQEDDFDYLNDLG
				PCFKRLANMFGSAVQPDN

984	(1-			MNYCFLKHWILMIPLLWPCL
	43)::			KVSETLKAEKARRTVPSTWR
	FLAG::mu			AKRDYKDDDDKAWVWRPFVV
	CDH 19			LEEMDDIQCVGKLRSDLDNG
	(44-323)::			NNSFQYKLLGIGAGSFSINE
	raCDH19			RTGEICAIQKLDREEKSLYI
	(324-			LRAQVIDTTIGKAVETESEF
	327)::			VIRVLDINDNEPRFLDEPYE
	muCDH1			AIVPEMSPEGTFVIKVTAND
	9(328-770)			ADDPSTGYHARILYNLERGQ
				PYFSVEPTTGVIRISSKMDR
				ELQDTYCVIIQAKDMLGQPG
				ALSGTTTVSIKLSDINDNKP
				IFKESFYRFTISESAPIGTS
				IGKIMAYDDDIGENAEMEYS
				IEDDDSKIFDIIIDNDTQEG
				IVILKKKVDFEHQNHYGIRA
				KVKNCHVDEELAPAHVNAST
				TYIKVQVEDEDEPPVFLLPY
				YILEIPEGKPYGTIVGTVSA
				TDPDRRQSPMRYYLTGSKMF
				DINDNGTIITTNMLDREVSA
				WYNLTVTATETYNVQQISSA
				HVYVQVFNINDNAPEFSQFY
				ETYVCENAESGEIVQIISAI
				DRDESIEDEHFYFNHSLEDT
				NNSSFMLTDNQDNTAVILSN
				RTGFNLKEEPVFYMIILIAD
				NGIPSLTSTNTLTIQVCDCG
				DSRNTETCANKGLLFIMGFR
				TEAIIAIMICVMVIFGFFFL
				ILALKQRRKETLFPEKTEDF
				RENIFCYDDEGGGEEDSEAF
				DIVELRQSTVMRERKPQRSK
				SAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDPCAPP
				FDSLQTFAYEGTGSSAGSLS
				SLASRDTDQEDDFDYLNDLG
				PRFKRLASMFGSAVQPNN

985	muCDH19(1-			MNYCFLKHWILMIPLLWPCL
	43)::			KVSETLKAEKARRTVPSTWR
	FLAG::mu			AKRDYKDDDDKAWVWRPFVV
	CDH19(44-			LEEMDDIQCVGKLRSDLDNG
	770)::			NNSFQYKLLGIGAGSFSINE
	raCDH19			RTGEICAIQKLDREEKSLYI
	(290, 299,			LRAQYIDTTIGKAVETESEF
	308)			VIRVLDINDNEPRFLDEPYE
				AIVPEMSPEGTFVIKVTAND
				ADDPSTGYHARILYNLERGQ
				PYFSVEPTTGVIRISSKMDR
				ELQDTYCVIIQAKDMLGQPG
				ALSGTTTVSIKLSDINDNKP
				IFKESFYRFTISESAPIGTS
				IGKIMAYDDDIGENAEMEYS
				IEDDDSKIFDIIIDNDTQEG
				IVILKKKVDFEQQSYYGIRA
				KVKNCHVDEELAPAHVNAST
				TYIKVQVEDEDEPFVFLLPY
				YILEIPEGKPYGTIVGTVSA
				TDPDRRQSPMRYYLTGSKMF
				DINDNGTIITTMMLDREVSA
				WYNLTVTATETYNVQQISSA
				HVYVQVFNINDNAPEFSQFY
				ETYVCENAESGEIVQIISAI
				DRDESIEDKHFYFNHSLEDT
				NNSSFMLTDNQDNIAVILSN
				RTGFNLKEEPVFYMIILIAD
				NGIPSLTSTNTLTIQVCDCG
				DSRNTETCANKGLLFIMGFR
				TEAIIAIMICVMVIFGFFFL
				ILALKQRRKETLFPEKTEDF
				RENIFCYDDEGGGEEDSEAF
				DIVELRQSTVMRERKPQRSK
				SAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDPCAPP
				FDSLQTFAYEGTGSSAGSLS
				SLASRDTDQEDDFDYLNDLG
				PRFKRLASMFGSAVQPNN

986	muCDH19(1-			MNYCFLKHWILMIPLLWPCL
	43)::			KVSETLKAEKARRTVPSTWR
	FLAG::mu			AKRDYKDDDDKAWVWRPFVV
	CDH19(44-			LEEMDDIQCVGKLRSDLDNG
	770)::			NNSPQYKLLGIGAGSFSINE
	huCDH1			RTGEICAIQKLDREEKSLYI
	9(271)			LRAQVIDTTIGKAVETESEF
				VIRVLDINDNEPRFLDEPYE
				AIVPEMSPEGTFVIKVTAND
				ADDPSTGYHARILYNLERGQ
				PYFSVEPTTGVIRISSKMDR
				ELQDTYCVIIQAKDMLGQPG
				ALSGTTTVSIKLSDINDNKP
				IFKESFYRFTISESAPTGTS
				IGKIMAYDDDIGENAEMEYS
				IEDDDSKIFDIIIDNDTQEG
				IVILKKKVDFEQQSYYGIRA
				KVKNCHVDEELAPAHVNAST
				TYIKVQVEDEDEPPVFLLPY
				YILEIPEGKPYGTIVGTVSA
				TDPDRRQSPMRYYLTGSKMF
				DINDNGTIITTNMLDREVSA
				WYNLTVTATETYNVQQISSA
				HVYVQVFNINDNAPEFSQFY
				ETYVCENAESGEIVQIISAI
				DRDESIEDHHFYFNHSLEDT
				NNSSFMLTDNQDNTAVILSN
				RTGFNLKEEPVFYMIILIAD
				NGIPSLTSTNTLTIQVCDCG
				DSRNTETCANKGLLFIMGFR
				TEAIIAIMICVMVIFGFFFL
				ILALKQRRKETLFPEKTEDF
				RENIFCYDDEGGGEEDSEAF
				DIVELRQSTVMRERKPQRSK
				SAEIRSLYRQSLQVGPDSAI
				FRKFILEKLEEANTDPCAPP
				FDSLQTFAYEGTGSSAGSLS
				SLASRDTDQEDDFDYLNDLG
				PRFKRLASMFGSAVQPNN

Claims

1. An isolated human antibody or antigen binding fragment thereof capable of binding to human cadherin 19 (CDH19) on the surface of a target cell, comprising a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:

(a) a VH region comprising CDR-H1 as set forth in SEQ ID NO: 94, CDR-H2 as set forth in SEQ ID NO: 95, CDR-H3 as set forth in SEQ ID NO: 96, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 262, CDR-L2 as set forth in SEQ ID NO: 263 and CDR-L3 as set forth in SEQ ID NO: 264,

(b) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 100, CDR-H2 as set forth in SEQ ID NO: 101, CDR-H3 as set forth in SEQ ID NO: 102, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 268, CDR-L2 as set forth in SEQ ID NO: 269 and CDR-L3 as set forth in SEQ ID NO: 270,

(c) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 118, CDR-H2 as set forth in SEQ ID NO: 119, CDR-H3 as set forth in SEQ ID NO: 120, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 286, CDR-L2 as set forth in SEQ ID NO: 287 and CDR-L3 as set forth in SEQ ID NO: 288,

(d) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 154, CDR-H2 as set forth in SEQ ID NO: 155, CDR-H3 as set forth in SEQ ID NO: 156, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 322, CDR-L2 as set forth in SEQ ID NO: 323 and CDR-L3 as set forth in SEQ ID NO: 324,

(e) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 100, CDR-H2 as set forth in SEQ ID NO: 101, CDR-H3 as set forth in SEQ ID NO: 912, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 268, CDR-L2 as set forth in SEQ ID NO: 269 and CDR-L3 as set forth in SEQ ID NO: 270,

(f) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 100, CDR-H2 as set forth in SEQ ID NO: 101, CDR-H3 as set forth in SEQ ID NO: 913, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 268, CDR-L2 as set forth in SEQ ID NO: 269 and CDR-L3 as set forth in SEQ ID NO: 270,

(g) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 94, CDR-H2 as set forth in SEQ ID NO: 95, CDR-H3 as set forth in SEQ ID NO: 910, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 262, CDR-L2 as set forth in SEQ ID NO: 263 and CDR-L3 as set forth in SEQ ID NO: 264,

(h) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 94, CDR-H2 as set forth in SEQ ID NO: 95, CDR-H3 as set forth in SEQ ID NO: 911, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 262, CDR-L2 as set forth in SEQ ID NO: 263 and CDR-L3 as set forth in SEQ ID NO: 264,

(i) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 118, CDR-H2 as set forth in SEQ ID NO: 119, CDR-H3 as set forth in SEQ ID NO: 120, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 286, CDR-L2 as set forth in SEQ ID NO: 287 and CDR-L3 as set forth in SEQ ID NO: 288,

(j) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 118, CDR-H2 as set forth in SEQ ID NO: 914, CDR-H3 as set forth in SEQ ID NO: 120, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 286, CDR-L2 as set forth in SEQ ID NO: 287 and CDR-L3 as set forth in SEQ ID NO: 288, and

(k) a VH region comprising CDR-H1 as set forth in CDR-H1 as set forth in SEQ ID NO: 154, CDR-H2 as set forth in SEQ ID NO: 155, CDR-H3 as set forth in SEQ ID NO: 920, and a VL region comprising CDR-L1 as set forth in SEQ ID NO: 322, CDR-L2 as set forth in SEQ ID NO: 323 and CDR-L3 as set forth in SEQ ID NO: 324.

2. The human antibody or antigen binding fragment thereof according to claim 1, wherein the antibody or antigen binding fragment thereof is a monoclonal antibody or a fragment thereof.

3. (canceled)

4. The human antibody or antigen binding fragment thereof according to claim 1, comprising a VH region comprising the amino acid sequence selected from the group consisting of:

SEQ ID NO: 338, SEQ ID NO: 354, SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484, SEQ ID NO: 501, SEQ ID NO: 502, SEQ ID NO: 503, SEQ ID NO: 504, SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 517, and SEQ ID NO: 518.

5. The human antibody or antigen binding fragment thereof according to claim 1, comprising a VL region comprising the amino acid sequence selected from the group consisting of:

SEQ ID NO: 394, SEQ ID NO: 410, SEQ ID NO: 434, SEQ ID NO: 412, SEQ ID NO: 571, SEQ ID NO: 572, SEQ ID NO: 573, SEQ ID NO: 574, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 578, SEQ ID NO: 579, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 598, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO: 601, SEQ ID NO: 612, and SEQ ID NO: 613.

6. The human antibody or antigen binding fragment thereof according to claim 1, comprising a VH region and a VL region comprising a pair of amino acid sequences selected from the group consisting of:

SEQ ID NOs: 338 and 394, SEQ ID NOs: 354 and 410, SEQ ID NOs: 378 and 434, SEQ ID NOs: 356 and 412, SEQ ID NOs: 476 and 571, SEQ ID NOs: 477 and 572, SEQ ID NOs: 478 and 573, SEQ ID NOs: 479 and 574, SEQ ID NOs: 480 and 575, SEQ ID NOs: 481 and 576, SEQ ID NOs: 482 and 577, SEQ ID NOs: 483 and 578, SEQ ID NOs: 484 and 579, SEQ ID NOs: 501 and 596, SEQ ID NOs; 502 and 597, SEQ ID NOs: 503 and 598, SEQ ID NOs: 504 and 599, SEQ ID NOs: 505 and 600, SEQ ID NOs: 506 and 601, SEQ ID NOs: 517 and 612, and SEQ ID NOs: 518 and 613.

7. The human antibody or antigen binding fragment thereof according to claim 6, wherein the human binding domain or antigen binding fragment thereof comprising a heavy and light chain amino acid sequence selected from the group consisting of:

SEQ ID NOs: 656 and 692, SEQ ID NOs: 654 and 690, SEQ ID NOs: 664 and 700, SEQ ID NOs: 670 and 706, SEQ ID NOs: 738 and 833, SEQ ID NOs: 739 and 834, SEQ ID NOs: 740 and 835, SEQ ID NOs: 741 and 836, SEQ ID NOs: 742 and 837, SEQ ID NOs: 743 and 838, SEQ ID NOs: 744 and 839, SEQ ID NOs: 745 and 840, SEQ ID NOs: 746 and 841, SEQ ID NOs: 763 and 858, SEQ ID NOs: 764 and 859, SEQ ID NOs: 765 and 860, SEQ ID NOs: 766 and 861, SEQ ID NOs: 767 and 862, SEQ ID NOs: 768 and 863, SEQ ID NOs: 779 and 874, and SEQ ID NOs: 780 and 875.

8. An antibody construct comprising the human antibody or antigen binding fragment thereof according to claim 1 conjugated to a chemotherapeutic agent.

9. The antibody construct according to claim 8, further comprising a linker, wherein the linker conjugates the chemotherapeutic agent to the human antibody or antigen binding fragment thereof.

10. The antibody construct according to claim 9, wherein the linker is a non-cleavable linker.

11. The antibody construct according to claim 10, wherein the linker comprises N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (MCC).

12. The antibody construct of claim 8, wherein the chemotherapeutic agent is conjugated to one or more lysines contained in the human antibody or antigen binding fragment thereof.

13. The antibody construct of claim 8, wherein the chemotherapeutic agent is maytansinoid (DM1).

14. The antibody construct of claim 13, wherein the average number of DM1 molecules per antibody construct is between 1 and 10.

15. The antibody construct of claim 13, wherein the average number of DM1 molecules per antibody construct is between 3 and 7.

16. The antibody construct of claim 13, wherein the average number of DM1 molecules per antibody construct is between 4 and 6.

17. The antibody construct of claim 13, wherein the average number of DM1 molecules per antibody construct is about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0.

18. An isolated nucleic acid molecule encoding the human antibody or antigen binding fragment thereof of claim 1.

19. A vector comprising the nucleic acid molecule of claim 18.

20. A host cell transformed or transfected with the nucleic acid molecule of claim 18.

21. A process for producing a human antibody or antigen binding fragment thereof, said process comprising culturing the host cell of claim 16 under conditions allowing the expression of the antibody or antigen binding fragment thereof.

22. The process of claim 21 further comprising recovering the produced antibody or antigen binding fragment thereof, and conjugating a chemotherapeutic agent to the recovered antibody or antigen binding fragment thereof to produce an antibody conjugate.

23. A composition comprising the human antibody or antigen binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier.

24-25. (canceled)

26. A method for treating or ameliorating a melanoma disease or metastatic melanoma disease, comprising administering to a subject in need thereof the antibody or antigen binding fragment thereof of claim 1.

27. The method according to claim 26, wherein the melanoma disease or metastatic melanoma disease is selected from the group consisting of superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, acral lentiginous melanoma and nodular melanoma.

28. A kit comprising the antibody or antigen binding fragment thereof of claim 1 in a vial or a syringe.