Anti-GPNMB antibodies and methods of use thereof

Abstract

The present disclosure relates generally to compositions comprising a monovalent antibody, e.g., a monoclonal monovalent antibody that specifically binds to a GPNMB polypeptide, such as a mammalian GPNMB polypeptide or a human GPNMB polypeptide, and the use of such compositions in treating an individual in need thereof.

Description

[0001] Sequence Listing

[0002] This application is filed with a sequence listing that is electronically submitted in XML format and is hereby incorporated by reference in its entirety. The sequence listing is provided as a file entitled "01209-0014-00PCT_ST26.xml" created on July 20, 2023, and is 524,000 bytes in size. Technical Field

[0003] The present disclosure relates to anti-GPNMB antibodies and uses (eg, therapeutic uses) of such antibodies. Background Art

[0004] Glycoprotein non-metastatic melanoma protein B (GPNMB), also known as osteoactivin (rat xenolog), dendritic cell-heparin integrin ligand (DC-HIL, mouse ortholog), or hematopoietic growth factor-induced neurokinin type 1 (HGFIN), is a type 1 transmembrane protein.

[0005] Increased expression of GPNMB is associated with a genome-wide significant risk for Parkinson's disease (Murthy et al., 2017, Neurogenetics, 18:121-133). The rs199347 SNP is associated with increased expression of GPNMB in the brain. GPNMB protein expression is associated with ALS and certain lysosomal storage disorders, including Gaucher's disease and Neimann-Pick disease type C (Tanaka et al., 2012, Sci Rep, 2:537; Kramer et al., 2016, FEBS Open Bio, 6:902-913; Marques et al., 2016, PLoS One 11:e0147208).

[0006] Additionally, GPNMB is upregulated in various cancers including glioblastoma multiforme, melanoma, and breast cancer (Tse et al., 2006, Clinical Cancer Res, 12:1373-1382; Kuan et al., 2006, Clinical Cancer Res, 12:1970-1982; Rose et al., 2007, Molecular Cancer Res, 5:1001-1014; Zhou et al., 2012, Neoplasma, 59:105; Taya and Hammes, 2018, Steroids, 133:102-107).

[0007] Anti-GPNMB antibodies have been previously described. See, for example, WO2006 / 071441, WO2007 / 053718, US2007 / 0190575, US2013 / 0156784, USPN 7,115,265, WO2008 / 133641, WO2010 / 135547, WO2016 / 145022, WO2017 / 046061, WO2018 / 217945, and WO2019 / 137138.

[0008] There is a need for new therapeutic anti-GPNMB antibodies with antagonistic activity that are effective in treating various diseases, disorders, and conditions associated with GPNMB, such as cancer, neurodegenerative disorders including Parkinson's disease, and lysosomal storage disorders.

[0009] All references cited herein, including patent applications and publications, are hereby incorporated by reference in their entirety. Summary of the Invention

[0010] The present disclosure generally relates to anti-GPNMB antibodies and methods of using such antibodies.

[0011] The present disclosure satisfies the need for novel therapeutic anti-GPNMB antibodies with antagonistic activity that are effective in treating conditions such as cancer, neurodegenerative disorders, and lysosomal storage disorders. Exemplary embodiments of the present disclosure include, inter alia, isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibodies, wherein the anti-GPNMB antibodies antagonize GPNMB activity. In some embodiments, the anti-GPNMB antibodies: modulate the expression of activation surface markers on myeloid cells, increase the cell surface expression of PD-L1 in human macrophages, increase the cell surface expression of CD40 in human macrophages, increase the cell surface expression of CD80 in human macrophages, modulate lysosomal function in myeloid cells, increase glucocerebrosidase activity in human macrophages, reduce the cell surface expression of GPNMB in human macrophages, alter the interferon pathway gene expression pattern in human macrophages, reduce tumor volume in a mouse tumor model, such as the MC38 model, reduce tumor growth rate in a mouse tumor model, such as the MC38 model, increase the level of IL-12p40 in serum, increase serum The invention relates to a novel GPNMB ligand-blocking antibody that antagonizes GPNMB activity and overcomes the decrease in glucocerebrosidase activity associated with the decrease in progranulin levels, reduces GPNMB expression levels in cells, optionally in macrophages, reduces LAMP2 expression levels in cells, optionally in macrophages, monocytes or neutrophils, inhibits or reduces inflammasome activation; inhibits IL-1β expression or release, reduces neuroinflammation, reduces the expression of C1q, GFAP, IBA1 and CTSD associated with neuroinflammation, and / or reduces lysosomal stress.

[0012] In some cases, the anti-GPNMB antibody is an antibody selected from GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN- 25. GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48 , GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97, GPN-98, and any combination thereof, compete for binding to GPNMB. In some instances, an anti-GPNMB antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain, the heavy chain variable domain, or both comprise at least one, at least two, at least three, at least four, at least five, or six HVRs selected from HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3 of an antibody selected from: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN- -30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, G PN-83, ​​GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98. In some cases: (a) HVR-H1 comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77;(b) HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 255, 256, 257, 258, 259, and 260; (c) HVR-H3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76, 79, 261, and 262; (d) HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: NO:83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 263, 264, 265, 266, 267 and 268; (e) HVR-L2 comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 263, 264, 265, 266, 267 and 268; NO:84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, 156, 269, 270, 271, 272, 273, 274, 275, 276, and 277; and / or (f) HVR-L3 comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, NO:85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, 157, 278, 279, 280, and 281. In some cases: HVR-H1 comprises the amino acid sequence of SEQ ID NO:5, HVR-H2 comprises the amino acid sequence of SEQ ID NO:6, HVR-H3 comprises the amino acid sequence of SEQ ID NO:7, HVR-L1 comprises the amino acid sequence of SEQ ID NO:83, HVR-L2 comprises the amino acid sequence of SEQ ID NO:84, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:85;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 8, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 9, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 10, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 86, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 87, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 88; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 11, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 12, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 13, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 89, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 90, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 91; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 14, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 15, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: NO:16, HVR-L1 comprises the amino acid sequence of SEQ ID NO:92, HVR-L2 comprises the amino acid sequence of SEQ ID NO:93, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:94; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:17, HVR-H2 comprises the amino acid sequence of SEQ ID NO:18, HVR-H3 comprises the amino acid sequence of SEQ ID NO:19, HVR-L1 comprises the amino acid sequence of SEQ ID NO:95, HVR-L2 comprises the amino acid sequence of SEQ ID NO:96, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:97; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:20, HVR-H2 comprises the amino acid sequence of SEQ ID NO:21, HVR-H3 comprises the amino acid sequence of SEQ ID NO:22, HVR-L1 comprises the amino acid sequence of SEQ ID NO:98, HVR-L2 comprises the amino acid sequence of SEQ ID NO:99, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: NO: 100; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 24, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 102, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 103;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 26, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 27, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 28, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 104, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 105, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 106; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 29, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 30, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 31, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 107, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 108, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 109; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 32, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 33, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: NO: 34, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 110, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 111, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 112; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 35, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 36, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 37, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 113, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 114, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 115; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 38, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 39, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 40, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 116, HVR-L2 comprises the amino acid sequence of SEQ ID NO: NO:117, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:118; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:41, HVR-H2 comprises the amino acid sequence of SEQ ID NO:42, HVR-H3 comprises the amino acid sequence of SEQ ID NO:43, HVR-L1 comprises the amino acid sequence of SEQ ID NO:119, HVR-L2 comprises the amino acid sequence of SEQ ID NO:120, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:121;or HVR-H1 comprises the amino acid sequence of SEQ ID NO:44, HVR-H2 comprises the amino acid sequence of SEQ ID NO:45, HVR-H3 comprises the amino acid sequence of SEQ ID NO:46, HVR-L1 comprises the amino acid sequence of SEQ ID NO:122, HVR-L2 comprises the amino acid sequence of SEQ ID NO:123, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:124; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:47, HVR-H2 comprises the amino acid sequence of SEQ ID NO:48, HVR-H3 comprises the amino acid sequence of SEQ ID NO:49, HVR-L1 comprises the amino acid sequence of SEQ ID NO:125, HVR-L2 comprises the amino acid sequence of SEQ ID NO:126, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:127; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:50, HVR-H2 comprises the amino acid sequence of SEQ ID NO:51, and HVR-H3 comprises the amino acid sequence of SEQ ID NO:52. NO: 52, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 128, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 129, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 130; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 53, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 54, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 55, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 131, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 132, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 133; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 56, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 57, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 58, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 134, HVR-L2 comprises the amino acid sequence of SEQ ID NO: NO:135, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:136; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:59, HVR-H2 comprises the amino acid sequence of SEQ ID NO:60, HVR-H3 comprises the amino acid sequence of SEQ ID NO:61, HVR-L1 comprises the amino acid sequence of SEQ ID NO:137, HVR-L2 comprises the amino acid sequence of SEQ ID NO:138, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:139;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 62, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 63, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 64, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 140, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 141, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 142; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 65, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 66, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 67, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 143, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 144, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 145; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 69, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: NO: 70, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 146, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 147, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 148; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 72, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 149, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 150, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 151; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 74, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 75, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 76, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 152, HVR-L2 comprises the amino acid sequence of SEQ ID NO: NO:153, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:154; or HVR-H1 comprises the amino acid sequence of SEQ ID NO:77, HVR-H2 comprises the amino acid sequence of SEQ ID NO:78, HVR-H3 comprises the amino acid sequence of SEQ ID NO:79, HVR-L1 comprises the amino acid sequence of SEQ ID NO:155, HVR-L2 comprises the amino acid sequence of SEQ ID NO:156, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:157; or;

[0013] HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 255, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 263, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 269, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 151; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 256, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 270, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 261, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 258, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 266, HVR-L2 comprises the amino acid sequence of SEQ ID NO: NO:272, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:278;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 261, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 261, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278 NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 279; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 261, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 258, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, and HVR-L1 comprises the amino acid sequence of SEQ ID NO: NO:264, HVR-L2 comprises the amino acid sequence of SEQ ID NO:272, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:278;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 280; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 259, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 19, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: NO: 262, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 274, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 281; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 262, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 274, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 262, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprises the amino acid sequence of SEQ ID NO: NO:275, and HVR-L3 comprises the amino acid sequence of SEQ ID NO:281;or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 262, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 276, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 262, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 277, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97; or HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprises the amino acid sequence of SEQ ID NO: HVR-L1 comprises the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97.

[0014] The present disclosure also relates to an isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region (VH) comprises: an HVR-H1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77; an HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77; and an HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 255, 256, 257, 258, 259 and 260; and an HVR-H3 comprising an amino acid sequence selected from any one of the following: SEQ ID NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76, 79, 261, and 262. In some instances, the light chain variable region (VL) comprises: an HVR-L1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 263, 264, 265, 266, 267, and 268; an HVR-L2 comprising an amino acid sequence selected from any one of SEQ ID NOs: NO:84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, 156, 269, 270, 271, 272, 273, 274, 275, 276 and 277; and an HVR-L3 comprising an amino acid sequence selected from any one of SEQ ID NO:84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, NO: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, 157, 278, 279, 280 and 281.In some cases, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239, and 240, and / or the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: A VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of any one of NOs: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 and 254. In some cases, the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, insertions, and / or deletions compared to the amino acid sequence selected from any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239, and 240, and / or the VL comprises a amino acid sequence selected from any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to the amino acid sequence of any one of NO:162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 and 254.In some cases, the antibody comprises a VH comprising an amino acid sequence selected from any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239, and 240, and / or comprises a VH comprising an amino acid sequence selected from any one of SEQ ID NOs: NO:162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 and 254.

[0015] The present disclosure further relates to isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibodies, wherein the anti-GPNMB antibody comprises: a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 7; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 83, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 84, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 8, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 9, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 86, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 87, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: NO: 88; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 12, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 13; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 89, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 90, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 14, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 15, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 16; and a VH comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 92, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 93, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: NO:94; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:17, HVR-H2 comprising the amino acid sequence of SEQ ID NO:18, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:19; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:95, HVR-L2 comprising the amino acid sequence of SEQ ID NO:96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:97;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 20, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 21, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 22; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 98, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 99, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 24, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 102, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103 NO: 26, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 27, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 28; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 105, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 29, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 30, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 31; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 107, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 108, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 109; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 109, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 210; NO: 32, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 33, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 34; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 110, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 111, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 112;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 35, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 113, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 115; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 38, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 40; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 116, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 118; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 116, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 118 NO: 41, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 42, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 43; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 119, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 120, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 121; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 44, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 45, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 46; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 123, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 124 NO:47, a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:48, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:49; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:125, HVR-L2 comprising the amino acid sequence of SEQ ID NO:126, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:127;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 50, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 51, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 52; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 128, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 129, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 130; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 53, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 131, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 132, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 134, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 135 NO: 56, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 57, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 58; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 134, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 135, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 136; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 59, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 60, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 61; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 137, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 138, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 139; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 139 NO: 62, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 63, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 140, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 141, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 142;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 66, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 67; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 143, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 144, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 145; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 69, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 70; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 146, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 147, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 148; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 146, NO: 71, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 72, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 149, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 150, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 151; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 74, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 75, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 76; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 152, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 153, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 154; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 154 NO: 77, a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 79; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 155, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 156, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 157;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 255, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 263, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 269, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 151; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 256, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 270, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 270, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, a VH comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278 NO: 71, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 258, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 266, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VL comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, NO: 71, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 73, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 279; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; or a VL comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, NO: 71, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 258, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 280; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 259, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 19, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; NO: 23, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 260, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 262, a VH comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 274, and a VL comprising HVR-L3 comprising the amino acid sequence of SEQ ID NO: 281; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 274, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 274, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97 NO: 23, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 260, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 262, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 275, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 281;or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 276, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 277, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VL comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, NO: 23, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262; and a VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 267, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97.

[0016] In some such cases, the antibody comprises: a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 161; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 163; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 165; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 167; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 169; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 171; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 173; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 175; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 177; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 179; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 181; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 183; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 185; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 187; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 193; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 195; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 197; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 199;a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 201; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 203; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 205; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 207; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 209; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 234; a VH at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 235; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 235; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 238; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 238; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 239; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240;A VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; or a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 240. In some cases, the antibody further comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 168; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 174; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 176; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 178; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 180; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 182; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 184; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 186; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 188; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192; a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194;a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 196; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 198; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 200; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 202; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 204; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 206; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 208; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 210; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 241; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 242; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 243; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 243; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 244; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 245; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 245; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 245; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 246; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 247; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 247; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 248; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 249;a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 250; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 251; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 252; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 253; a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 254; or a VL at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 249. In yet other cases, the antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 161; a VH comprising the amino acid sequence of SEQ ID NO: 163; a VH comprising the amino acid sequence of SEQ ID NO: 165; a VH comprising the amino acid sequence of SEQ ID NO: 167; a VH comprising the amino acid sequence of SEQ ID NO: 169; a VH comprising the amino acid sequence of SEQ ID NO: 171; a VH comprising the amino acid sequence of SEQ ID NO: 173; a VH comprising the amino acid sequence of SEQ ID NO: 175; a VH comprising the amino acid sequence of SEQ ID NO: 177; a VH comprising the amino acid sequence of SEQ ID NO: 179; a VH comprising the amino acid sequence of SEQ ID NO: 181; a VH comprising the amino acid sequence of SEQ ID NO: 183; a VH comprising the amino acid sequence of SEQ ID NO: 185; a VH comprising the amino acid sequence of SEQ ID NO: 187; a VH comprising the amino acid sequence of SEQ ID NO: 189; a VH comprising the amino acid sequence of SEQ ID NO: 190 a VH comprising the amino acid sequence of SEQ ID NO: 191; a VH comprising the amino acid sequence of SEQ ID NO: 193; a VH comprising the amino acid sequence of SEQ ID NO: 195; a VH comprising the amino acid sequence of SEQ ID NO: 197; a VH comprising the amino acid sequence of SEQ ID NO: 199; a VH comprising the amino acid sequence of SEQ ID NO: 201; a VH comprising the amino acid sequence of SEQ ID NO: 203; a VH comprising the amino acid sequence of SEQ ID NO: 205; a VH comprising the amino acid sequence of SEQ ID NO: 207; a VH comprising the amino acid sequence of SEQ ID NO: 209; a VH comprising the amino acid sequence of SEQ ID NO: 234; a VH comprising the amino acid sequence of SEQ ID NO: 235;A VH comprising the amino acid sequence of SEQ ID NO: 236; a VH comprising the amino acid sequence of SEQ ID NO: 237; a VH comprising the amino acid sequence of SEQ ID NO: 238; a VH comprising the amino acid sequence of SEQ ID NO: 236; a VH comprising the amino acid sequence of SEQ ID NO: 237; a VH comprising the amino acid sequence of SEQ ID NO: 236; a VH comprising the amino acid sequence of SEQ ID NO: 237; a VH comprising the amino acid sequence of SEQ ID NO: 238; a VH comprising the amino acid sequence of SEQ ID NO: 236; a VH comprising the amino acid sequence of SEQ ID NO: 239; a VH comprising the amino acid sequence of SEQ ID NO: 240; a VH comprising the amino acid sequence of SEQ ID NO: 240; a VH comprising the amino acid sequence of SEQ ID NO: 240; a VH comprising the amino acid sequence of SEQ ID NO: 240; or a VH comprising the amino acid sequence of SEQ ID NO: 240. And in yet other cases, the antibody comprises: a VL comprising the amino acid sequence of SEQ ID NO: 162; a VL comprising the amino acid sequence of SEQ ID NO: 164; a VL comprising the amino acid sequence of SEQ ID NO: 166; a VL comprising the amino acid sequence of SEQ ID NO: 168; a VL comprising the amino acid sequence of SEQ ID NO: 170; a VL comprising the amino acid sequence of SEQ ID NO: 172; a VL comprising the amino acid sequence of SEQ ID NO: 174; a VL comprising the amino acid sequence of SEQ ID NO: 176; a VL comprising the amino acid sequence of SEQ ID NO: 178; a VL comprising the amino acid sequence of SEQ ID NO: 180; a VL comprising the amino acid sequence of SEQ ID NO: 182; a VL comprising the amino acid sequence of SEQ ID NO: 184; a VL comprising the amino acid sequence of SEQ ID NO: 186; a VL comprising the amino acid sequence of SEQ ID NO: 188; a VL comprising the amino acid sequence of SEQ ID NO: 190; a VL comprising the amino acid sequence of SEQ ID NO: a VL comprising the amino acid sequence of SEQ ID NO: 192; a VL comprising the amino acid sequence of SEQ ID NO: 194; a VL comprising the amino acid sequence of SEQ ID NO: 196; a VL comprising the amino acid sequence of SEQ ID NO: 198; a VL comprising the amino acid sequence of SEQ ID NO: 200; a VL comprising the amino acid sequence of SEQ ID NO: 202; a VL comprising the amino acid sequence of SEQ ID NO: 204; a VL comprising the amino acid sequence of SEQ ID NO: 206;a VL comprising the amino acid sequence of SEQ ID NO: 208; a VL comprising the amino acid sequence of SEQ ID NO: 210; a VL comprising the amino acid sequence of SEQ ID NO: 241; a VL comprising the amino acid sequence of SEQ ID NO: 242; a VL comprising the amino acid sequence of SEQ ID NO: 243; a VL comprising the amino acid sequence of SEQ ID NO: 243; a VL comprising the amino acid sequence of SEQ ID NO: 244; a VL comprising the amino acid sequence of SEQ ID NO: 245; a VL comprising the amino acid sequence of SEQ ID NO: 246; a VL comprising the amino acid sequence of SEQ ID NO: 247; a VL comprising the amino acid sequence of SEQ ID NO: 247; a VL comprising the amino acid sequence of SEQ ID NO: 248; a VL comprising the amino acid sequence of SEQ ID NO: 249; a VL comprising the amino acid sequence of SEQ ID NO: 250; a VL comprising the amino acid sequence of SEQ ID NO: 251; a VL comprising the amino acid sequence of SEQ ID NO: 252; a VL comprising the amino acid sequence of SEQ ID NO: 253; a VL comprising the amino acid sequence of SEQ ID NO: 254 a VL comprising the amino acid sequence of SEQ ID NO: 253; a VL comprising the amino acid sequence of SEQ ID NO: 254; or a VL comprising the amino acid sequence of SEQ ID NO: 249. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 161 and a VL comprising the amino acid sequence of SEQ ID NO: 162 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 163 and a VL comprising the amino acid sequence of SEQ ID NO: 164 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 165 and a VL comprising the amino acid sequence of SEQ ID NO: 166 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 167 and a VL comprising the amino acid sequence of SEQ ID NO: 168 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 169 and a VL comprising the amino acid sequence of SEQ ID NO: 170 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 171 and a VL comprising the amino acid sequence of SEQ ID NO: 172 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 173 and a VL comprising the amino acid sequence of SEQ ID NO: 174 a VH comprising the amino acid sequence of SEQ ID NO: 175, and a VL comprising the amino acid sequence of SEQ ID NO: 176 (as shown in Table 1);a VH comprising the amino acid sequence of SEQ ID NO: 177 and a VL comprising the amino acid sequence of SEQ ID NO: 178 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 179 and a VL comprising the amino acid sequence of SEQ ID NO: 180 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 181 and a VL comprising the amino acid sequence of SEQ ID NO: 182 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 183 and a VL comprising the amino acid sequence of SEQ ID NO: 184 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 185 and a VL comprising the amino acid sequence of SEQ ID NO: 186 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 187 and a VL comprising the amino acid sequence of SEQ ID NO: 188 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 189 and a VL comprising the amino acid sequence of SEQ ID NO: 190 NO: 190 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 191 and a VL comprising the amino acid sequence of SEQ ID NO: 192 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 193 and a VL comprising the amino acid sequence of SEQ ID NO: 194 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 195 and a VL comprising the amino acid sequence of SEQ ID NO: 196 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 197 and a VL comprising the amino acid sequence of SEQ ID NO: 198 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 199 and a VL comprising the amino acid sequence of SEQ ID NO: 200 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 201 and a VL comprising the amino acid sequence of SEQ ID NO: 202 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 203 and a VL comprising the amino acid sequence of SEQ ID NO: 204 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 205 and a VL comprising the amino acid sequence of SEQ ID NO: 206 NO: 203, and a VL comprising the amino acid sequence of SEQ ID NO: 204 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 205, and a VL comprising the amino acid sequence of SEQ ID NO: 206 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 207, and a VL comprising the amino acid sequence of SEQ ID NO: 208 (as shown in Table 1); a VH comprising the amino acid sequence of SEQ ID NO: 209, and a VL comprising the amino acid sequence of SEQ ID NO: 210 (as shown in Table 1);a VH comprising the amino acid sequence of SEQ ID NO: 234 and a VL comprising the amino acid sequence of SEQ ID NO: 241 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 235 and a VL comprising the amino acid sequence of SEQ ID NO: 242 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 237 and a VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 238 and a VL comprising the amino acid sequence of SEQ ID NO: 244 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 245 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 237 and a VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 238 and a VL comprising the amino acid sequence of SEQ ID NO: 244 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 245 (as shown in Table 15); NO: 245 amino acid sequence (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 246 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 237 and a VL comprising the amino acid sequence of SEQ ID NO: 247 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 238 and a VL comprising the amino acid sequence of SEQ ID NO: 247 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 248 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 239 and a VL comprising the amino acid sequence of SEQ ID NO: 249 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 250 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 251 NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 251 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 252 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 253 (as shown in Table 15); a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 254 (as shown in Table 15);or a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 249 (as shown in Table 15). ;

[0017] In some embodiments, the antibody comprises a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 290; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 291; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 292; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 293; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 294; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 295; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 296; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 297; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 298; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 299; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 300; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 301; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 302; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 303; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 304; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 305; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 306; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 307; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 308; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 309;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 310; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 311; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 312; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 313; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 314; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 315; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 316; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 316; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 317; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 318; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 319; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 320; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 321; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 322; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 323; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 324; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 325; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 326; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 327; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 328; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 329;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 343; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 344; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 345; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 346; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 347; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 348; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 349;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 352; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 362; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 363; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 364; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 365; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 366; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 367; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 368;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 369; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 370; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 371; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 372; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 373; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 374; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 375; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 375; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 376; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 377; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 378; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 379; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 380; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 381; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 382; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 383; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 384; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 385; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 386; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 387; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 388;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 389; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 390; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 391; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 392; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 393; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 394; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 395; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 395; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 396; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 397; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:402; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:403; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:404; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:405; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:406; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:407; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:408;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 412; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 413; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 414; or a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 415. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of NO:415. In some embodiments, the antibody comprises a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:422; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:423; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:424; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:425; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:426; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:427; a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:428;A light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; or a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433. In some embodiments, the antibody comprises a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 290 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 291 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 292 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; NO: 293 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 294 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 295 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 296 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of NO:416;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 297 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 298 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 299 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; NO: 300 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 301 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 302 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 303 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 304 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 305 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 306 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 307 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 308 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 309 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; NO: 310 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 311 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 312 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 313 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 314 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 315 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 316 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 317 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 318 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 319 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; NO: 320 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 321 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 322 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 323 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 324 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 325 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 346 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; NO: 350 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; NO: 360 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 362 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 363 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 364 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 365 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 366 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 367 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 368 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 369 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; NO: 370 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 371 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 372 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 373 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 374 and a light chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 375 and a light chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 376 and a light chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 420;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 377 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 378 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 379 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; NO: 346 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; NO: 356 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 346 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; NO: 350 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; NO: 360 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 362 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 363 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 364 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 365 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 366 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 367 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 368 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 369 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; NO: 370 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 371 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 372 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 373 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 374 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 375 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 376 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 377 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 378 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 379 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 380 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 381 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; NO: 382 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 383 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 384 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 385 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 386 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 387 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 388 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 389 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 390 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 391 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; NO: 392 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 393 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 394 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 395 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 396 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 397 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; NO:402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:406. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; NO:412 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:413 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:414 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:415 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:416. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; NO:404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:408. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; NO:400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:404. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; NO:406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; NO:402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:406. a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433;a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; a heavy chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; NO:408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: A light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of NO:433.

[0018] In some embodiments, the disclosure herein relates to an anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody comprising: a heavy chain comprising the amino acid sequence of SEQ ID NO: 290 or SEQ ID NO: 291, and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 292 or SEQ ID NO: 293, and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 294 or SEQ ID NO: 295, and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 296 or SEQ ID NO: 297, and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 298 or SEQ ID NO: 299, and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 300 or SEQ ID NO: 301, and a light chain comprising the amino acid sequence of SEQ ID NO: 302 or SEQ ID NO: 303; NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 302 or SEQ ID NO: 303 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 304 or SEQ ID NO: 305 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 306 or SEQ ID NO: 307 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; a heavy chain comprising the amino acid sequence of SEQ ID NO: 308 or SEQ ID NO: 309 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 310 or SEQ ID NO: 311 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 312 or SEQ ID NO: 313 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 314 or SEQ ID NO: 315 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 314 or SEQ ID NO: 315 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 316 or SEQ ID NO: 317 and a light chain comprising the amino acid sequence of SEQ ID NO: 417;a heavy chain comprising the amino acid sequence of SEQ ID NO: 318 or SEQ ID NO: 319 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 320 or SEQ ID NO: 321 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 322 or SEQ ID NO: 323 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 324 or SEQ ID NO: 325 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; a heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 418; a heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347 and a light chain comprising the amino acid sequence of SEQ ID NO: 419;a heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: NO: 361 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 362 or SEQ ID NO: 363 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 364 or SEQ ID NO: 365 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 366 or SEQ ID NO: 367 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 368 or SEQ ID NO: 369 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 370 or SEQ ID NO: 371 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 372 or SEQ ID NO: 373 and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 374 or SEQ ID NO: 375 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 376 or SEQ ID NO: 377 and a light chain comprising the amino acid sequence of SEQ ID NO: 420;a heavy chain comprising the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 379 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; a heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: NO: 337, and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339, and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341, and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343, and a light chain comprising the amino acid sequence of SEQ ID NO: 421; a heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345, and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347, and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349, and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 422;a heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: 361 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; a heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: NO: 331, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341, and a light chain comprising the amino acid sequence of SEQ ID NO: 423; a heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343, and a light chain comprising the amino acid sequence of SEQ ID NO: a heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347 and a light chain comprising the amino acid sequence of SEQ ID NO: 424;a heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; a heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: NO: 361, and a light chain comprising the amino acid sequence of SEQ ID NO: 424; a heavy chain comprising the amino acid sequence of SEQ ID NO: 362 or SEQ ID NO: 363, and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 364 or SEQ ID NO: 365, and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 366 or SEQ ID NO: 367, and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 368 or SEQ ID NO: 369, and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 370 or SEQ ID NO: 371, and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 372 or SEQ ID NO: 373, and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 374 or SEQ ID NO: 375 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 376 or SEQ ID NO: 377 and a light chain comprising the amino acid sequence of SEQ ID NO: 425;a heavy chain comprising the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 379 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; a heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: a heavy chain comprising the amino acid sequence of SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; a heavy chain comprising the amino acid sequence of SEQ ID NO: 380 or SEQ ID NO: 381 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 382 or SEQ ID NO: 383 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 384 or SEQ ID NO: 385 and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 386 or SEQ ID NO: 387 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 388 or SEQ ID NO: 389 and a light chain comprising the amino acid sequence of SEQ ID NO: 427;a heavy chain comprising the amino acid sequence of SEQ ID NO: 390 or SEQ ID NO: 391 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 392 or SEQ ID NO: 393 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 394 or SEQ ID NO: 395 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 396 or SEQ ID NO: 397 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 428; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 429;a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: NO: 415, and a light chain comprising the amino acid sequence of SEQ ID NO: 429; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399, and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401, and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403, and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405, and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407, and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409, and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 430;a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: a heavy chain comprising the amino acid sequence of SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 432;a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; a heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; a heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; or a heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: The light chain of the amino acid sequence of NO:433.

[0019] In yet other embodiments, the disclosure herein relates to an anti-GPNMB antibody comprising a VH comprising HVR-H1, HVR-H2, and HVR-H3 of any of the following antibodies and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of any of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN -84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98. In some cases, the antibody comprises a VH and / or VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to a VH and / or VL of any of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98. In some cases, the antibody comprises the VH and / or VL of any of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84,GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98. In some cases, the antibody comprises: a VH and a VL, wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-01 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-01 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-03 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-03 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-06 wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-08 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-08 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-08 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-08 (as shown in Table 3). or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-09 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-09 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-11 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-11 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-22 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-22 wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-24 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-24 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-25 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-25.HVR-L2 and HVR-L3 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-26 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-26 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-30 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-30 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-31 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-31 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-33 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-33 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-34 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-34 (as shown in Table 3); or wherein VH comprises HVR-H1 of antibody GPN-35 , HVR-H2 and HVR-H3 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-35 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-37 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-37 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-38 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-38 (as shown in Table 3) or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-41 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-41 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-42 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-42 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-43 (as shown in Table 2) and VL comprises HVR-L1, HVR-H2, and HVR-L3 of antibody GPN-43.or wherein VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-48 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-48 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-52 (as shown in Table 2) and VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-52 (as shown in Table 3); or wherein VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-61 (as shown in Table 2) and VL comprises HVR-L1, HVR-H2 and HVR-L3 of antibody GPN-61 (as shown in Table 2) wherein the VH comprises HVR-L1, HVR-H2 and HVR-H3 of antibody GPN-65 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-65 (as shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-81 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-81 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-82 -H2 and HVR-H3 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-82 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-83 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-83 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-84 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-84 (as shown in Table 17); or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-85 (as shown in Table 16) and VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-85 (as shown in Table 17); or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-86 (as shown in Table 16) and VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-86 (as shown in Table 17); or wherein VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-87 (as shown in Table 16) and VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-87HVR-L2 and HVR-L3 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-88 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-88 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-89 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-89 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-90 (as shown in Table 16) ) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-90 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-91 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-91 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-92 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-92 (as shown in Table 17); or wherein the VH comprises HVR-H1 of antibody GPN-93 , HVR-H2, and HVR-H3 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-93 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-94 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-94 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-95 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-95 (as shown in Table 17) or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-96 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-96 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-97 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-97 (as shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-98 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-98HVR-L2 and HVR-L3 (as shown in Table 17).

[0020] In some cases, the antibodies herein antagonize GPNMB activity. In some embodiments, the anti-GPNMB antibodies: regulate the expression of activation surface markers on myeloid cells, increase the cell surface expression of PD-L1 in human macrophages, increase the cell surface expression of CD40 in human macrophages, increase the cell surface expression of CD80 in human macrophages, regulate lysosomal function in myeloid cells, increase glucocerebrosidase activity in human macrophages, reduce the cell surface expression of GPNMB in human macrophages, change the expression pattern of interferon pathway genes in human macrophages, reduce tumor volume in mouse tumor models, such as the MC38 model, reduce tumor growth rate in mouse tumor models, such as the MC38 model, increase the level of IL-12p40 in serum, increase serum The invention relates to a novel GPNMB ligand-blocking antibody that antagonizes GPNMB activity and overcomes the decrease in glucocerebrosidase activity associated with the decrease in progranulin levels, reduces GPNMB expression levels in cells, optionally in macrophages, reduces LAMP2 expression levels in cells, optionally in macrophages, monocytes or neutrophils, inhibits or reduces inflammasome activation; inhibits IL-1β expression or release, reduces neuroinflammation, reduces the expression of C1q, GFAP, IBA1 and CTSD associated with neuroinflammation, and / or reduces lysosomal stress.

[0021] In some embodiments, the antibody binds to human GPNMB, binds to mouse GPNMB, binds to cynomolgus monkey GMNMB, binds to both human and mouse GPNMB, or binds to human, mouse, and cynomolgus monkey GPNMB. In some embodiments, the antibody binds to human GPNMB with an affinity of about 0.4 nM to about 120 nM, about 0.3 nM to about 5 nM, about 0.4 nM to about 1.04 nM, about 0.14 to about 0.65 nM and binds to mouse GPNMB with an affinity of about 0.18 nM to about 0.44 nM.

[0022] In some cases, the antibody is a monoclonal antibody, a humanized antibody, an antigen-binding fragment, such as Fab, Fab', Fab'-SH, F(ab')2, Fv or scFv fragment, or a bispecific or multispecific antibody. In some cases, the antibody belongs to IgG classification, IgM classification or IgA classification, such as human IgG1, IgG2, IgG3 or IgG4 isotype or mouse IgG1 or IgG2 isotype. In some cases, the antibody binds to inhibitory Fc receptors, such as inhibitory Fc-gamma receptor IIB (FcgRIIB). In some cases, the antibody reduces the cellular level of FcgRIIB. In some cases, the antibody has a human or mouse IgG1 isotype and comprises one or more amino acid substitutions at an amino acid residue in the Fc region selected from the group consisting of: N297A, D265A, D270A, L234A, L235A, G237A, P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E233P, L234V, L234F, L235E, P331S, P331G, S2 440Y, S440W, and any combination thereof, wherein the numbering of the residues is according to the EU numbering. In some cases, the antibody has a human or mouse IgG2 isotype and comprises one or more amino acid substitutions at an amino acid residue in the Fc region selected from the group consisting of A330S, C127S, C214S, C219S, C220S, E345K, E345Q, E345R, E345Y, E430F, E430G, E430S, E430T, G237A, H268Q, L328F, M252Y, P331S, S254T, S267E, S440W, S440Y, T256E, V234A, V309L, and any combination thereof, wherein the numbering of the residues is according to EU numbering.In some cases, the antibody has a human or mouse IgG4 isotype and comprises one or more amino acid substitutions at an amino acid residue in the Fc region selected from the group consisting of: C127S, E318A, E345R, E430G, F234A, G237A, K322A, L235A, L235E, L236E, L243A, L328F, M252Y, P331S, S228P, S229P, S254T, S267E, S440Y, T256E, and any combination thereof, wherein the numbering of the residues is according to EU numbering.

[0023] The antibody of any one of claims 1 to 54, wherein the antibody comprises one or more amino acid substitutions at residue positions in the Fc region selected from the group consisting of: A330L, A330S, C127S, E345R, E430G, K322A, L234A, L234F, L235A, L235E, L243A, L328F, P331S, S267E, S440Y, and any combination thereof, wherein the numbering of amino acid residues is according to EU or Kabat numbering. In some cases, the IgG Fc amino acid sequence is selected from the group consisting of SEQ ID NOs: 213-233.

[0024] The present disclosure also relates to pharmaceutical compositions comprising an anti-GPNMB antibody as described herein and a pharmaceutically acceptable carrier, as well as isolated nucleic acids comprising nucleic acid sequences encoding an anti-GPNMB antibody as described herein, isolated vectors comprising nucleic acids, and isolated host cells comprising nucleic acids or vectors. The present disclosure further relates to methods for producing anti-GPNMB antibodies, comprising culturing host cells to produce the antibodies, and optionally further recovering the antibodies produced by the cells.

[0025] The present disclosure further relates to a method for treating a cancer of a subject in need, the method including administering a therapeutically effective amount of the anti-GPNMB antibodies herein to an individual in need, so as to treat cancer. In some cases, the method further includes administering one or more therapeutic agents, such as checkpoint inhibitors, such as PD1, PD-L1 and PD-L2 inhibitors, such as anti-PD-L1 antibodies, anti-PD-L2 antibodies and anti-PD-1 antibodies. In some cases, cancer is sarcoma, bladder cancer, breast cancer, colon cancer, endometrial cancer, kidney cancer (kidney cancer / renal cancer), leukemia, lung cancer, non-small cell lung cancer, melanoma, lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, gastric cancer, thyroid cancer, uterine cancer, liver cancer, cervical cancer, testicular cancer, squamous cell carcinoma, glioma, glioblastoma, adenoma or neuroblastoma. In some cases, cancer is glioblastoma multiforme, bladder cancer, esophageal cancer or triple negative breast cancer.

[0026] The present disclosure further relates to methods of treating a neurodegenerative disease or condition in a subject in need thereof, comprising administering to an individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody described herein, thereby treating the disease or condition. In some cases, the disease or condition is selected from Parkinson's disease, Alzheimer's disease, and ALS.

[0027] The present disclosure also relates to methods of treating a lysosomal storage disease or disorder in a subject in need thereof, comprising administering to an individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody described herein, thereby treating the disease or disorder. In some instances, the lysosomal storage disease is Gaucher disease.

[0028] The present disclosure also relates to methods for detecting the presence of GPNMB in an in vitro sample or individual, the methods comprising the anti-GPNMB antibodies described herein. In some cases, the methods further comprise quantifying the antigen-bound anti-GPNMB antibodies.

[0029] It should be understood that one, some or all of the features of the various embodiments described herein can be combined to form other embodiments of the present disclosure. These and other aspects of the present disclosure will become apparent to those skilled in the art. These and other aspects of the present disclosure are further described by the following specific embodiments. In some aspects, provided herein is a method for detecting GPNMB in a sample, comprising contacting the sample with any one of the anti-GPNMB antibodies described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] This U.S. provisional application contains at least one drawing in color. If a non-provisional or PCT application is published in the future claiming priority to this U.S. provisional application and incorporating the content of this provisional application, copies of this provisional patent application with color drawings will be provided by the Patent Office upon request and payment of the necessary fee.

[0031] Figure 1 The amino acid alignment of human (SEQ ID NO: 1), mouse (SEQ ID NO: 435), and cynomolgus monkey (SEQ ID NO: 434) GPNMB is illustrated.

[0032] Figure 2A and Figure 2B Set forth are data showing that the anti-GPNMB antibodies of the present disclosure bind to Freestyle 293 cells expressing human GPNMB and to B16F10 cells expressing mouse GPNMB, respectively. Figure 2C Data showing that anti-GPNMB antibodies of the present disclosure bind to U937 cells expressing GPNMB are set forth.

[0033] Figure 3A and Figure 3BSet forth are data showing titration curves of anti-GPNMB antibodies of the present disclosure binding to Freestyle 293 cells expressing human GPNMB and to B16F10 cells expressing mouse GPNMB, respectively.

[0034] Figure 4A 、 Figure 4J Data showing binding of soluble mouse GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types are illustrated.

[0035] Figures 5A to 5C Data showing the effects of the anti-GPNMB antibodies of the present disclosure on blocking or enhancing the binding of soluble mouse GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to SVEC cells are presented.

[0036] Figures 6A to 6G Data showing that the anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 in macrophages are set forth. Figure 6H Data showing the effect of JAK kinase inhibitors on the increased cell surface PDL1 expression induced by the anti-GPNMB antibodies of the present disclosure are presented.

[0037] Figure 7A and Figure 7B Set forth are data showing the effect of the anti-GPNMB antibodies of the present disclosure on increasing glucocerebrosidase activity in macrophages.

[0038] Figure 8A and Figure 8B Data showing that anti-GPNMB antibodies of the present disclosure induce internalization of cell surface GPNMB are presented.

[0039] Figure 9 Data showing binning results of anti-GPNMB antibodies of the present disclosure binding to GPNMB are set forth.

[0040] Figure 10 Data showing various GPNMB chimeric polypeptide constructs comprising human and mouse GPNMB domains are illustrated.

[0041] Figures 11A to 11C Data showing that genetic depletion of GPNMB in M1 and M2 polarized macrophages results in an increase in interferon response pathways of chemokines and cytokines are presented.

[0042] Figure 12A and Figure 12B Set forth are data showing the effects of the anti-GPNMB antibody GPN-61 on differential gene expression of various genes associated with the interferon signaling pathway in human macrophages.

[0043] Figure 13A and Figure 13B Data showing reduced tumor growth in GPNMB knockout mice and GPNMB heterozygous knockout mice in an in vivo mouse tumor model are presented.

[0044] Figure 14A and Figure 14B Illustrated are data showing GPNMB expression in macrophages and monocytes as measured by scRNAseq analysis. Figure 14C Data showing that GPNMB heterozygosity results in a reduction in the number of suppressor-like monocytes from cluster 2 (myeloid-derived suppressor cells, CD14+) are illustrated. 14D to 14F Data showing that GPNMB heterozygosity results in differential gene expression patterns in cluster 3 (CD8+ T cells), cluster 0 (C1QC+ macrophages), and cluster 9 (proliferating T cells), respectively, are illustrated.

[0045] Figure 15A and Figure 15B Data showing that the anti-GPNMB antibody GPN-61 reduces tumor volume in vivo in a mouse tumor model are presented.

[0046] Figure 16A and Figure 16B Data showing reduced glucocerebrosidase activity in granulocytes and monocytes / macrophages in wild-type and progranulin knockout mice, respectively, are presented. Figure 16C

[00145] Data are presented showing that treatment of progranulin knockout mice with the anti-GPNMB antibody GPN-61 results in higher glucocerebrosidase activity in monocytes compared to that observed in GRN- / - mice treated with an isotype control antibody.

[0047] Figure 17A and Figure 17B

[00145] Data are presented showing that treatment of wild-type mice or progranulin knockout mice with the anti-GPNMB antibody GPN-61 results in increased serum levels of IL-12p40 and CCL5, respectively, compared to that observed in isotype control antibody-treated animals.

[0048] Figure 18 Illustrated are data showing a heat map comparing differentially expressed genes from GPNMB knockout mice (WT-KO), GPNMB knockout mice treated with CBE (GpnmbKO CBE), and wild-type mice treated with CBE (Gpnmb WT CBE).

[0049] 19A to 19DSet forth are data showing a comparison of selected antiviral, interferon-related genes (Stat2, Irf9, Cxcl16, and Ifit3b) that exhibit differential expression in wild-type (WT) mice and GPNMB knockout mice (GpnmbKO) treated with CBE.

[0050] Figure 20A presents data showing increased expression of complement component 1q (C1q), glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA1), and cathepsin D (CatD) in the cortex of wild-type or GPNMB knockout mice treated with or without cyclohexene tetraol B-epoxide (CBE); Figures 20B to 20E Explain that from Figure 20A The relative intensity data of the expressed proteins; Figure 20F Data showing an increase in serum CXC motif chemokine ligand 1 (CXCL1) in wild-type or GPNMB knockout mice treated with or without CBE are presented.

[0051] Figure 21A illustrates data showing increased IL-1β expression in human macrophages stimulated with LPS + nigericin (to activate inflammasomes); Figure 21B Set forth are data showing that anti-GPNMB antibodies of the present disclosure inhibit inflammasome activation in human macrophages as measured by changes in IL-1β expression.

[0052] Figure 22A and Figure 22B

[00145] Data showing that anti-GPNMB antibodies of the present disclosure reduce IL-1β expression in human macrophages following inflammasome activation with LPS+nigericin are presented.

[0053] Figure 23A and Figure 23B Data showing the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in reducing inflammasome activation in human macrophages are presented.

[0054] Figure 24A and Figure 24B illustrating data showing increased lysosomal stress in human macrophages stimulated with rapamycin, as measured by Lysotracker fluorescent staining; Figure 24C and Figure 24D Set forth data showing differences in lysosomal stress responses in mouse bone marrow-derived macrophages obtained from wild-type or GPNMB knockout mice in the presence or absence of rapamycin; Figure 24E and Figure 24F Data showing the effects of the anti-GPNMB antibodies of the present disclosure on the lysosomal stress response in human macrophages are presented.

[0055] 25A to 25D Data showing that affinity-matured anti-GPNMB antibodies of the present disclosure effectively reduce rapamycin-induced lysosomal stress in human macrophages are presented.

[0056] Figures 26A to 26C

[00145] Data showing the effects of anti-GPNMB antibodies of the present disclosure with different Fc variants on reducing rapamycin-induced lysosomal stress in human macrophages are presented.

[0057] 27A to 27D Data showing that affinity-matured anti-GPNMB antibodies of the present disclosure increase the expression of PDL1 and CD40 in human macrophages are presented.

[0058] 28A to 28D Data showing the effects of anti-GPNMB antibodies of the present disclosure with different Fc variants on increasing the expression of PDL1 and CD40 in human macrophages are presented.

[0059] Figures 29A to 29C Data showing that anti-GPNMB antibodies of the present disclosure with different Fc variants increase GC enzyme activity in human macrophages are presented.

[0060] Figures 30A to 30C Data showing that the anti-GPNMB antibodies of the present disclosure reduce expression of the mature form of the GPNMB protein in human macrophages are set forth.

[0061] Figures 31A to 31C Data showing that the anti-GPNMB antibodies of the present disclosure reduce expression of the mature form of the GPNMB protein in human macrophages are set forth.

[0062] Figures 32A to 32C Data showing that anti-GPNMB antibodies GPN-41 and GPN-65 reduce expression of both mature and immature forms of GPNMB protein in human macrophages are presented.

[0063] Figure 33A and Figure 33B Data showing that the anti-GPNMB antibodies of the present disclosure reduce LAMP-2 levels in splenocytes, macrophages, monocytes, and neutrophils are presented.

[0064] Figures 34A to 34D Data showing that the anti-GPNMB antibodies of the present disclosure increase GC enzyme activity in primary microglia, splenic macrophages, neutrophils, monocytes, and macrophages are presented. DETAILED DESCRIPTION

[0065] The present disclosure relates to anti-GPNMB antibodies (eg, monoclonal antibodies); methods of making and using such antibodies; pharmaceutical compositions comprising such antibodies; nucleic acids encoding such antibodies; and host cells comprising nucleic acids encoding such antibodies.

[0066] The techniques and procedures described or referred to herein are generally well understood by those skilled in the art and are routinely used using conventional methods, such as, for example, widely utilized methods such as those described in Sambrook et al. Molecular Cloning: A Laboratory Manual 3rd ed. (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (FM Ausubel et al., eds., (2003); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000).

[0067] definition

[0068] Unless otherwise indicated, the terms "GPNMB" or "GPNMB polypeptide" or "GPNMB protein" used interchangeably herein refer herein to any natural GPNMB from any vertebrate source including mammals such as primates (e.g., humans and cynomolgus monkeys (cyno)) and rodents (e.g., mice and rats). GPNMB is also known as osteoactivin (rat ortholog), dendritic cell-heparin integrin ligand (DC-HIL, mouse ortholog) or hematopoietic growth factor-induced neurokinin-1 type (HGFIN). In some embodiments, the term encompasses both wild-type sequences and naturally occurring variant sequences, e.g., splice variants or allelic variants. In some embodiments, the term encompasses "full-length", unprocessed GPNMB and any form of GPNMB produced by processing in cells. In some embodiments, GPNMB is human GPNMB. As used herein, the term "human GPNMB" refers to a polypeptide having the amino acid sequence of SEQ ID NO: 1.

[0069] The terms "anti-GPNMB antibody," "antibody that binds to GPNMB," and "antibody that specifically binds to GPNMB" refer to antibodies that are capable of binding to GPNMB with sufficient affinity to allow the antibody to be used as a diagnostic and / or therapeutic agent targeting GPNMB. In one embodiment, the extent of binding of the anti-GPNMB antibody to an unrelated, non-GPNMB polypeptide is about 10% or less of the binding of the antibody to GPNMB, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, the antibody that binds to GPNMB has an affinity of <1 μM, <100 nM, <10 nM, <1 nM, <0.1 nM, <0.01 nM, or <0.001 nM (e.g., 10 -8 M or less, such as 10 -8 M to 10 -13 M, for example 10 -9 M to 10 -13 In certain embodiments, the anti-GPNMB antibody binds to an epitope of GPNMB that is conserved among GPNMBs from different species.

[0070] With respect to the binding of an antibody to a target molecule, the term "specific binding" or "specifically binds to" or "has specificity for" a particular polypeptide or an epitope on a particular polypeptide target means binding that is significantly different from non-specific interactions. Specific binding can be measured, for example, by measuring the binding of a molecule compared to the binding of a control molecule. For example, specific binding can be measured by competing with a control molecule similar to the target (e.g., an excess of unlabeled target). In this case, if the binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target, specific binding is indicated. The term "specific binding" or "specifically binds to" or "has specificity for" a particular polypeptide or an epitope on a particular polypeptide target as used herein can be measured, for example, by having about 10 -4 M or lower, 10 -5 M or lower, 10 -6 M or lower, 10 -7 M or lower, 10 -8 M or lower, 10 -9 M or lower, 10 -10 M or lower, 10 -11 M or lower, 10 -12 KD of any one of M or lower or 10 - 4 M to 10 -6 M or 10 -6 M to 10 -10 M or 10 -7 M to 10 -9Affinity is expressed as a molecule with a KD in the range of 4 M. As will be appreciated by those skilled in the art, affinity and KD values ​​are inversely correlated. High affinity for an antigen is measured by a low KD value. In one embodiment, the term "specific binding" refers to binding wherein a molecule binds to a specific polypeptide or epitope on a specific polypeptide and does not substantially bind to any other polypeptide or polypeptide epitope.

[0071] The terms "immunoglobulin" (Ig) and "antibody" are used interchangeably herein. The term "antibody" is used herein in the broadest sense and specifically encompasses monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) (including those formed from at least two intact antibodies), and antigen-binding antibody fragments, so long as the antigen-binding antibody fragment exhibits the desired biological activity.

[0072] "Native antibodies" are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light ("L") chains and two identical heavy ("H") chains. Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (V) at one end. H ), followed by a number of constant domains. Each light chain has a variable domain at one end (V L ) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. It is believed that specific amino acid residues form an interface between the light chain and the heavy chain variable domain.

[0073] For the structure and properties of different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th edition, Daniel P. Stites, Abba I. Terr, and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, page 71 and Chapter 6.

[0074] The light chains from any vertebrate species can be assigned to one of two clearly distinct types, called kappa ("κ") and lambda ("λ"), based on the amino acid sequence of their constant domains. Immunoglobulins can be assigned to different classes or isotypes depending on the amino acid sequence of the constant domain of their heavy chains (CH). There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, whose heavy chains are designated alpha ("α"), delta ("δ"), epsilon ("ε"), gamma ("γ"), and muon ("μ"), respectively. The γ and α classes are further divided into subclasses (isotypes) based on relatively minor differences in CH sequence and function, for example, humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known and generally described in, for example, Abbas et al., Cellular and Molecular Immunology, 4th ed. (WB Saunders Co., 2000).

[0075] The "variable region" or "variable domain" of an antibody, such as the anti-GPNMB antibodies of the present disclosure, refers to the amino-terminal domain of the heavy or light chain of the antibody. The variable domains of the heavy and light chains may be referred to as "V H ” and “V L These domains are generally the most variable parts of an antibody (relative to other antibodies of the same class) and contain the antigen-binding site.

[0076] The term "variable" refers to the fact that certain segments of variable domains are widely different in sequence in antibodies (such as anti-GPNMB antibodies of the present disclosure). The variable domain mediates antigen binding and limits the specificity of a particular antibody to its specific antigen. However, variability is not evenly distributed in the entire span of the variable domain. On the contrary, it is concentrated in three segments called hypervariable regions (HVRs) in both light and heavy chain variable domains. The more highly conserved part of the variable domain is called framework region (FR). The variable domains of native heavy and light chains each include four FR areas, which mainly adopt a β-sheet configuration and are connected by three HVRs, which form a loop connecting β-sheet structures and forming a part of β-sheet structures in some cases. The HVR in each chain is tightly held together by the FR area and promotes the formation of the antigen binding site of the antibody together with the HVR from another chain (see Kabat et al., Sequences of Immunological Interest, Fifth Edition, National Institute of Health, Bethesda, MD (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity.

[0077] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous antibody population, such as the monoclonal anti-GPNMB antibody of the present disclosure, that is, the individual antibodies constituting the population are identical except for possible naturally occurring mutations and / or post-translational modifications (such as isomerization, amidation, etc.) that may exist in trace amounts. Monoclonal antibodies are highly specific for a single antigenic site. In contrast to polyclonal antibody preparations that typically include different antibodies for different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to its specificity, the advantage of monoclonal antibodies is that they are synthesized by hybridoma culture without being contaminated by other immunoglobulins. The modifier "monoclonal" indicates that the characteristic of the antibody is obtained from a substantially homogeneous antibody population and should not be considered as requiring antibody production by any ad hoc method. For example, the monoclonal antibodies to be used in accordance with the present invention can be made by a variety of techniques, including, but not limited to, one or more of the following methods: methods of immunizing animals (including, but not limited to, rats, mice, rabbits, guinea pigs, hamsters, and / or chickens) with one or more of DNA, virus-like particles, polypeptides, and / or cells, hybridoma methods, B-cell cloning methods, recombinant DNA methods, and techniques for producing human or human-like antibodies in animals that have partial or complete human immunoglobulin loci or genes encoding human immunoglobulin sequences.

[0078] The terms "full-length antibody," "intact antibody," or "whole antibody" are used interchangeably to refer to an antibody in its substantially complete form, as opposed to an antibody fragment, such as an anti-GPNMB antibody. Specifically, a full-length antibody includes antibodies having two heavy chains and two light chains comprising an Fc region. The constant domains may be native sequence constant domains (e.g., human native sequence constant domains) or amino acid sequence variants thereof. In some cases, a complete antibody may have one or more effector functions.

[0079] The term "monovalent antibody" or "one-armed antibody" refers to an antibody having a single antigen-binding recognition domain that is specific for a target antigen (i.e., the antibody comprises no more than one antigen-binding domain). In some embodiments, the single antigen-binding domain comprises a single variable region heavy chain polypeptide and a single variable region light chain polypeptide. An antibody that is "monovalent" for a target comprises no more than one antigen-binding domain for that target.

[0080] "Antibody fragment" refers to a molecule that is not an intact antibody but comprises a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies (see U.S. Patent 5,641,870, Example 2; Zapata et al., Protein Eng. 8(10):1057-1062 (1995)); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

[0081] As used herein, the terms "antigen binding domain," "antigen binding region," "antigen binding site" and similar terms refer to the portion of an antibody molecule comprising the amino acid residues that confer specificity to the antibody molecule for an antigen (e.g., hypervariable region (HVR)).

[0082] Papain digestion of antibodies (such as the anti-GPNMB antibodies of the present disclosure) produces two identical antigen-binding fragments, called "Fab" fragments, and a residual "Fc" fragment (the name reflects the ability to crystallize readily). The Fab fragment consists of an intact light chain together with the variable region domain (V) of the heavy chain. H ) and the first constant domain of a heavy chain (C H 1) Composition. Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen binding site. Pepsin treatment of an antibody produces a single, larger F(ab')2 fragment that roughly corresponds to two disulfide-linked Fab fragments with different antigen binding activities and is still capable of cross-linking antigen. Fab' fragments differ from Fab fragments in that the C HThe constant domains have a few additional residues at the carboxyl terminus, including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine ​​residues of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments that have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0083] The Fc fragment comprises the carboxyl-terminal portions of two heavy chains held together by disulfide bonds.The effector functions of antibodies are determined by sequences in the Fc region, which is also recognized by Fc receptors (FcR) found on certain types of cells.

[0084] A "functional fragment" of an antibody (such as the anti-GPNMB antibodies of the present disclosure) comprises a portion of an intact antibody, generally including the antigen binding or variable region of the intact antibody or an Fc region of an antibody that retains or has modified FcR binding ability. Examples of antibody fragments include linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0085] The term "diabodies" refers to small antibody fragments prepared by: H With V L scFv fragments are constructed with short linkers (about 5-10 residues) between the domains to achieve interchain, rather than intrachain, pairing of the variable domains, thereby generating bivalent fragments, i.e., fragments with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" sFv fragments, where the V H and V L Domains are present on different polypeptide chains.

[0086] As used herein, "chimeric antibody" refers to an antibody (immunoglobulin), such as the chimeric anti-GPNMB antibody of the present disclosure, in which a portion of the heavy and / or light chain is identical or homologous to the corresponding sequence in an antibody derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain is identical or homologous to the corresponding sequence in an antibody derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity. The chimeric antibodies of interest herein include Antibodies, wherein the antigen binding region of the antibody is derived from an antibody produced by, for example, immunizing macaques with an antigen of interest. As used herein, "humanized antibodies" are used as a subset of "chimeric antibodies."

[0087] " Humanized " form of non-human (e.g., mouse) antibody (such as the humanized form of anti-GPNMB antibody of the present disclosure) is a chimeric antibody comprising amino acid residues from non-human HVR and amino acid residues from people FR. In certain embodiments, humanized antibody will comprise substantially all of at least one and typically two variable domains, wherein all or substantially all of HVR (e.g., CDR) correspond to those of non-human antibodies, and all or substantially all of FR correspond to those of people antibodies. Humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a people antibody. " Humanized form " of an antibody (e.g., non-human antibody) refers to an antibody that has undergone humanization.

[0088] "Human antibody" refers to an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human (such as the anti-GPNMB antibody of the present disclosure) and / or an antibody produced using any of the techniques for producing human antibodies as disclosed herein. This definition of human antibody explicitly excludes humanized antibodies comprising non-human antigen-binding residues. Human antibodies can be produced using a variety of techniques known in the art, including phage display libraries and yeast display libraries. Human antibodies can be prepared by administering antigens to transgenic animals (e.g., immune xenogeneic mice) that are modified to produce such antibodies in response to antigen attack but whose endogenous loci have been disabled, as well as produced via human B cell hybridoma technology.

[0089] The term "hypervariable region," "HVR," or "HV" when used herein refers to regions of an antibody variable domain (such as the anti-GPNMB antibodies of the present disclosure) that are highly variable in sequence and / or form structurally defined loops. Generally, antibodies comprise six HVRs; three in V H (H1, H2, H3), and three in V L (L1, L2, L3). In natural antibodies, H3 and L3 display the greatest diversity of the six HVRs, and H3 in particular is believed to play a unique role in conferring fine specificity to antibodies. Naturally occurring camelid antibodies composed solely of heavy chains are functional and stable in the absence of light chains.

[0090] Many HVRs are used and encompassed herein to describe. In some embodiments, HVRs may be Kabat complementarity determining regions (CDRs) and are most commonly used (Kabat et al., supra) based on sequence variability. In some embodiments, HVRs may be Chothia CDRs. Chothia refers to the position of a structural loop (Chothia and Lesk J. Mol. Biol. 196: 901-917 (1987)). In some embodiments, HVRs may be AbM HVRs. AbM HVRs represent a compromise between Kabat CDRs and Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software. In some embodiments, HVRs may be "contact" HVRs. "Contact" HVRs are based on analysis of available complex crystal structures. The residues from each of these HVRs are noted below.

[0091]

[0092] An HVR may comprise an "extended HVR" as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) in VL, and 26-35 (H1), 50-65 or 49-65 (preferred embodiments) (H2), and 93-102, 94-102, or 95-102 (H3) in VH. Variable domain residues are numbered according to Kabat et al., supra, for each of these extended HVR definitions.

[0093] "Framework" or "FR" residues are those variable domain residues other than the HVR residues as herein defined.

[0094] As used herein, an "acceptor human framework" is a human immunoglobulin framework comprising a V L or V H The acceptor human framework "derived from" a human immunoglobulin framework or a human consensus framework may comprise the same amino acid sequence thereof, or it may comprise pre-existing amino acid sequence changes. In some embodiments, the number of pre-existing amino acid changes is 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less or 2 or less. When pre-existing amino acid changes are present in VH, preferably those changes occur only at three, two or one of positions 71H, 73H and 78H; for example, the amino acid residues at those positions may be changed to 71A, 73T and / or 78A. In one embodiment, the VL acceptor human framework is identical in sequence to the V L The framework sequences are identical to those of human immunoglobulins or human consensus framework sequences.

[0095] "Human consensus framework" refers to the selection of human immunoglobulin V L or V H The framework sequence is the framework of the most frequently occurring amino acid residues. L or V H The sequence is selected from a subset of variable domain sequences. Generally, the subset of sequences is as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991). Examples include sequences for V L , the subgroup may be subgroup κI, κII, κIII or κIV as in Kabat et al., supra. H , the subgroup can be subgroup I, subgroup II or subgroup III as in Kabat et al., supra.

[0096] For example, an "amino acid modification" at a specified position of an anti-GPNMB antibody of the present disclosure refers to a substitution or deletion of the specified residue, or the insertion of at least one amino acid residue adjacent to the specified residue. Insertion "adjacent" to a specified residue means insertion within one to two residues of the specified residue. Insertion can be at the N-terminus or C-terminus of the specified residue. Preferably, the amino acid modification herein is substitution.

[0097] "Fv" is the smallest antibody fragment that contains a complete antigen recognition site and binding site. This fragment consists of a dimer of a heavy chain variable region domain and a light chain variable region domain tightly non-covalently associated. The folding of these two domains produces six hypervariable loops (3 loops each from the H chain and the L chain), which contribute amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three antigen-specific HVRs) is able to recognize and bind to antigen, but with lower affinity than the complete binding site.

[0098] "Single-chain Fv" also abbreviated as "sFv" or "scFv" is an antibody fragment comprising the VH and VL antibody domains linked in a single polypeptide chain. Preferably, the sFv polypeptide further comprises a VH domain and a VL domain. H With V L A polypeptide linker between the domains that enables the sFv to form the desired structure for antigen binding.

[0099] Antibody "effector functions" refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype.

[0100] The term "Fc region" is used herein to define the C-terminal region of a heavy chain immunoglobulin, including native sequence Fc regions and variant Fc regions. Although the boundaries of the Fc region of a heavy chain immunoglobulin may vary, the human IgG heavy chain Fc region is typically defined as extending from the amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. The C-terminal lysine (residue 447, according to the EU numbering system) in the Fc region can be removed, for example, during the production or purification of an antibody or by recombinant engineering encoding the nucleic acid of the heavy chain of an antibody. Therefore, the composition of a complete antibody can include an antibody population that removes all K447 residues, an antibody population that does not remove the K447 residue, and an antibody population with and without a mixture of antibodies containing the K447 residue. Suitable native sequence Fc regions for use in antibodies of the present disclosure include human IgG1, IgG2, IgG3, and IgG4.

[0101] A "native sequence Fc region" comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature. Native sequence human Fc regions include native sequence human IgG1 Fc regions (non-A and A allotypes); native sequence human IgG2 Fc regions; native sequence human IgG3 Fc regions; and native sequence human IgG4 Fc regions, as well as naturally occurring variants thereof.

[0102] A "variant Fc region" comprises an amino acid sequence that differs from the amino acid sequence of a native sequence Fc region due to at least one amino acid modification, preferably one or more amino acid substitutions. Preferably, the variant Fc region has at least one amino acid substitution, e.g., from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions, in a native sequence Fc region or in the Fc region of a parent polypeptide, compared to a native sequence Fc region or to the Fc region of a parent polypeptide. The variant Fc region herein will preferably have at least 80% homology to a native sequence Fc region and / or to the Fc region of a parent polypeptide, and most preferably at least 90% homology thereto, and more preferably at least 95% homology thereto.

[0103] "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. Preferably, FcR is a native sequence human FcR. In addition, preferably, FcR is an FcR (gamma receptor) that binds to an IgG antibody and includes receptors of the FcγRI, FcγRII and FcγRIII subclasses, including allelic variants and alternative splicing forms of these receptors, FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences, the main difference being their cytoplasmic domains. Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif ("ITAM") in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif ("ITIM") in its cytoplasmic domain. In this article, the term "FcR" encompasses other FcRs, including those to be identified in the future. FcR can also increase the serum half-life of antibodies.

[0104] As used herein, "percentage (%) of amino acid sequence identity" and "percentage (%) of homology" with respect to peptide, polypeptide or antibody sequences refers to the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in a particular peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percentage sequence identity, and any conservative substitutions are not considered part of the sequence identity. Alignment for the purpose of determining percent amino acid sequence identity can be performed in a variety of ways that are within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGN TM (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms known in the art needed to achieve maximal alignment over the full length of the sequences being compared.

[0105] The term "compete" when used in the context of antibodies that compete for the same epitope or overlapping epitopes means competition between antibodies as determined by an assay in which the antibody being tested prevents or inhibits (e.g., reduces) specific binding of a reference molecule (e.g., a ligand or reference antibody) to a common antigen (e.g., GPNMB or a fragment thereof). Various types of competitive binding assays can be used to determine whether an antibody competes with another antibody, for example: solid phase direct or indirect radioimmunoassays (RIA), solid phase direct or indirect enzyme immunoassays (EIA), sandwich competition assays (see, e.g., Stahli et al., 1983, Methods in Enzymology 9:242-253); solid phase direct biotin-avidin EIA (see, e.g., Kirkland et al., 1986, J. Immunol. 137:3614-3619); solid phase direct label assays, solid phase direct label sandwich assays (see, e.g., Harlow and Lane, 1988, Antibodies, A Laboratory Manual, Cold Spring Harbor Press); solid phase direct label RIA using an I-125 label (see, e.g., Morel et al., 1988, Molec. Immunol. 25:7-15); solid phase direct biotin-avidin EIA (see, e.g., Cheung et al., 1990, Virology 176:546-552); and direct label RIA (Moldenhauer et al., 1990, Scand. J. Immunol. 32:77-82). Typically, this assay involves the use of purified antigen bound to a solid surface or cell carrying any one of these unlabeled test antibodies and labeled reference antibodies. Competitive inhibition is measured by determining the amount of label bound to the solid surface or cell in the presence of the test antibody. Typically, the test antibody is present in excess. Antibodies identified by competition assays (competing antibodies) include antibodies that bind to the same epitope as the reference antibody, and antibodies that bind to adjacent epitopes that are close enough to the epitope bound by the reference antibody to cause steric hindrance. Typically, when the competing antibody is present in excess, it will inhibit (e.g., reduce) the specific binding of the reference antibody to the common antigen by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5% and / or approaching 100%.

[0106] As used herein, an "interaction" between a GPNMB polypeptide and a second polypeptide encompasses, but is not limited to, protein-protein interactions, physical interactions, chemical interactions, binding, covalent binding, and ionic binding. As used herein, an antibody "inhibits an interaction between two polypeptides" when it disrupts, reduces, or completely eliminates the interaction between the two polypeptides. An antibody of the present disclosure "inhibits an interaction between the two polypeptides" when it binds to one of the two polypeptides. In some embodiments, the interaction may be inhibited by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5%, and / or nearly 100%.

[0107] The term "epitope" includes any determinant capable of being bound by an antibody. An epitope is a region of an antigen to which an antibody that targets the antigen binds, and when the antigen is a polypeptide, includes specific amino acids that directly contact the antibody. In most cases, epitopes are located on polypeptides, but in some cases, they may be located on other types of molecules such as nucleic acids. Epitope determinants may include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl or sulfonyl groups, and may have specific three-dimensional structural characteristics and / or specific charge characteristics. In general, an antibody specific for a particular target antigen will preferentially recognize an epitope on the target antigen in a complex mixture of polypeptides and / or macromolecules.

[0108] An "isolated" antibody (such as an isolated anti-GPNMB antibody of the present disclosure) is one that has been identified, separated, and / or recovered from components of its production environment (e.g., naturally or recombinantly). Preferably, the isolated antibody is free from association with all other contaminating components from its production environment. Contaminating components from its production environment (such as components produced by recombinant transfected cells) are materials that would typically interfere with the research, diagnostic, or therapeutic use of the antibody and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the antibody will be purified: (1) to greater than 95% by weight of the antibody as determined by, for example, the Lowry method, and in some embodiments to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence as determined by use of a spinning cup sequenator, or (3) to homogeneity as determined by SDS-PAGE performed under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant T cells since at least one component of the antibody's natural environment will not be present. However, isolated polypeptide or antibody ordinarily will be prepared by at least one purification step.

[0109] An "isolated" nucleic acid molecule encoding an antibody (such as an anti-GPNMB antibody of the present disclosure) is a nucleic acid molecule that has been identified and separated from at least one contaminating nucleic acid molecule with which it is normally associated in its production environment. Preferably, the isolated nucleic acid is not associated with all components associated with the production environment. The isolated nucleic acid molecules encoding the polypeptides and antibodies herein are in a form that is different from the form in which they are found or set in nature. Thus, the isolated nucleic acid molecules are different from the nucleic acids encoding the polypeptides and antibodies herein that are naturally present in cells.

[0110] As used herein, the term "vector" is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid connected thereto. One type of vector is a "plasmid", which refers to a circular double-stranded DNA in which an additional DNA segment can be joined. Another type of vector is a phage vector. Another type of vector is a viral vector, in which an additional DNA segment can be joined to a viral genome. Some vectors can replicate autonomously in the host cell into which they are introduced (for example, bacterial vectors and episomal mammalian vectors with bacterial replication origins). Other vectors (for example, non-episomal mammalian vectors) can be integrated into the genome of the host cell when introduced into the host cell, thereby replicating together with the host genome. In addition, some vectors can guide the expression of the gene operably connected thereto. Such vectors are referred to herein as "recombinant expression vectors", or simply as "expression vectors". Generally speaking, expression vectors with practicality in recombinant DNA technology are generally in the form of plasmids. In this specification, "plasmid" and "vector" are used interchangeably because plasmids are the most commonly used vector forms.

[0111] As used interchangeably herein, "polypeptide" or "nucleic acid" refers to polymers of nucleotides of any length, and includes DNA and RNA. The nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or analogs thereof, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction.

[0112] "Host cell" includes individual cells or cell cultures that can be or have been recipients of vectors for incorporating polynucleotide inserts. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. Host cells include cells transfected in vivo with a polynucleotide of the invention.

[0113] As used herein, "carrier" includes pharmaceutically acceptable carriers, excipients, or stabilizers that are non-toxic to cells or mammals exposed thereto at the dosages and concentrations employed.

[0114] As used herein, the term "treatment" refers to a clinical intervention designed to alter the natural course of the individual being treated during the course of clinical pathology. Desirable therapeutic effects include reducing the rate of progression of a particular disease, condition, or disorder, ameliorating or lessening its pathological state, and alleviating or improving its prognosis. For example, a subject is successfully "treated" if one or more symptoms associated with a particular disease, condition, or disorder are alleviated or eliminated.

[0115] "Effective amount" refers to an amount that effectively achieves the desired therapeutic result at least under the necessary dosage and time period. The effective amount can be provided in one or more administrations. The effective amount is also the amount in which any toxic or harmful effects of the treatment are exceeded by the beneficial effects of the treatment. For therapeutic use, beneficial or desired results include the following clinical results, such as alleviating one or more symptoms caused by the disease, increasing the quality of life of the person suffering from the disease, reducing the dosage of other agents required for treating the disease, enhancing the effect of another agent (such as via targeting), delaying the progression of the disease and / or prolonging survival. The effective amount of a drug, compound or pharmaceutical composition is an amount sufficient to directly or indirectly achieve therapeutic treatment. As should be understood in clinical situations, the effective amount of a drug, compound or pharmaceutical composition may be combined or may not be combined with another drug, compound or pharmaceutical composition to achieve. Therefore, "effective amount" can be considered in the case of administering one or more therapeutic agents, and if the desired result can be achieved or achieved in combination with one or more other agents, it is considered that a single dose of an effective amount is given.

[0116] For treatment purposes, a "subject" refers to any animal classified as a mammal, including humans, livestock and farm animals, and zoo, sport, or pet animals, such as dogs, horses, rabbits, cows, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. In some embodiments, the subject is a human.

[0117] As used herein, administration "in conjunction with" or "in combination with" another compound or composition includes simultaneous administration and / or administration at different times. Administration in conjunction with or in combination also encompasses administration as a co-formulation or as separate compositions, including at different dosing frequencies or time intervals, and using the same route of administration or different routes of administration. In some embodiments, administration in conjunction with is administration as part of the same treatment regimen.

[0118] As used herein, the term "about" refers to the typical error range for individual values ​​readily known to those skilled in the art. Reference herein to "about" a value or parameter includes (and describes) embodiments for the value or parameter itself.

[0119] Unless the context clearly indicates otherwise, as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents. For example, a reference to an "antibody" is a reference to one or more antibodies, such as molar amounts, and includes equivalents thereof known to those skilled in the art.

[0120] It is to be understood that aspects and embodiments of the present disclosure described herein include "comprising," "consisting of," and "consisting essentially of" aspects and embodiments.

[0121] Anti-GPNMB antibody

[0122] Provided herein are monovalent anti-GPNMB antibodies. The antibodies provided herein can be used, for example, to treat GPNMB-related disorders.

[0123] In one aspect, the present disclosure provides an isolated (e.g., monoclonal) antibody that binds to an epitope within a GPNMB protein or polypeptide of the present disclosure. The GPNMB protein or polypeptide of the present disclosure includes, but is not limited to, a mammalian GPNMB protein or polypeptide, a human GPNMB protein or polypeptide, a mouse (rat) GPNMB protein or polypeptide, and a cynomolgus monkey GPNMB protein or polypeptide. The GPNMB protein and polypeptide of the present disclosure include naturally occurring variants of GPNMB. In some embodiments, the GPNMB protein and polypeptide of the present disclosure are membrane-bound. In some embodiments, the GPNMB protein and polypeptide of the present disclosure are soluble extracellular domains of GPNMB.

[0124] In some embodiments, GPNMB is expressed in cells. In some embodiments, GPNMB is expressed in myeloid cells, including but not limited to phagocytes, microglia, macrophages, dendritic cells, osteoclasts, oligodendrocytes and melanocytes. In addition, GPNMB is shown to be ectopic or overexpressed in a variety of cancers (Linger et al., 2008, Adv Cancer Res, 100: 35-83).

[0125] In some aspects, the anti-GPNMB antibodies of the disclosure bind to human GPNMB, bind to mouse GPNMB, bind to cynomolgus monkey GMNMB, bind to both human and mouse GPNMB, or bind to human, mouse, and cynomolgus monkey GPNMB.

[0126] In some aspects, the anti-GPNMB antibodies of the present disclosure bind to human GPNMB with an affinity of about 0.4nM to about 120nM. In some aspects, the anti-GPNMB antibodies of the present disclosure bind to mouse GPNMB with an affinity of about 0.3nM to about 5nM. In some aspects, the anti-GPNMB antibodies of the present disclosure bind to cynomolgus monkey GPNMB with an affinity of about 0.4nM to about 1.04nM. In other aspects, the anti-GPNMB antibodies of the present disclosure bind to human GPNMB with an affinity of about 0.14 to about 0.65nM and bind to mouse GPNMB with an affinity of about 0.18nM to about 0.44nM.

[0127] In some aspects, the anti-GPNMB antibodies of the present disclosure are antagonistic antibodies. In some aspects, the anti-GPNMB antibodies of the present disclosure increase the expression level of PDL1 (for example, in macrophages); increase the expression level of CD40 (for example, in macrophages); increase the expression level of CD80 (for example, in macrophages); increase the serum cytokine expression levels of IL-12p40 and CCL5. In some aspects, the anti-GPNMB antibodies of the present disclosure promote macrophage activation.

[0128] In some aspects, the anti-GPNMB antibodies of the present disclosure increase the expression level of GC enzyme (e.g., in macrophages). In some aspects, the anti-GPNMB antibodies of the present disclosure are effective in overcoming the reduction in GC enzyme activity associated with reduced progranulin levels.

[0129] In some aspects, the anti-GPNMB antibodies of the present disclosure reduce the expression level of GPNMB in cells (e.g., macrophages). In some aspects, the anti-GPNMB antibodies of the present disclosure reduce the expression level of LAMP2 in cells (e.g., macrophages, monocytes, neutrophils).

[0130] In some aspects, the anti-GPNMB antibodies of the present disclosure inhibit or reduce inflammasome activation. In some aspects, the anti-GPNMB antibodies of the present disclosure inhibit IL-1β expression or release.

[0131] In some aspects, the anti-GPNMB antibodies of the present disclosure reduce neuroinflammation. In some aspects, the anti-GPNMB antibodies of the present disclosure reduce the expression of C1q, GFAP, IBA1, and CTSD, which are associated with neuroinflammation.

[0132] In some aspects, the anti-GPNMB antibodies of the present disclosure reduce lysosomal stress.

[0133] GPNMB protein

[0134] Human GPNMB is a type 1 transmembrane glycoprotein that appears as two polypeptide isoforms due to alternative splicing, one with 572 amino acids and the shorter with 560 amino acids. GPNMB has 12 glycosylation sites, a polycystic kidney disease (PKD) domain, an integrin recognition (RGD) motif, an immunoreceptor tyrosine-based activation-like motif (ITAM-like) and a lysosomal targeting (dileucine) motif (Abdelmagid et al., 2008, Exp Cell Res, 314: 2334-2351). GPNMB can be cleaved by metalloproteinase ADAM10, releasing soluble fragments that can be bound to various receptors and trigger cellular responses (Rose et al., 2010, PLoS One, 5 (8): e12093).

[0135] GPNMB, lysosomal dysfunction, and Parkinson's disease

[0136] Glucocerebrosidase is a lysosomal β-glucosidase that degrades glucosylceramide. Hereditary deficiency of glucocerebrosidase is the cause of autosomal recessive Gaucher disease, the most common lysosomal storage disease (Brady et al., 1966, J Clin Invest, 45: 1112-1115). This disease is caused by mutations in the lysosomal hydrolase β-glucosidase glucocerebrosidase that lead to accumulation of its substrate glucosylceramide (van der Lienden et al., 2018, Int Journal of Molecular Sciences, 20: 66). Hereditary deficiency of glucocerebrosidase is also a risk factor for Parkinson's disease and Lewy body dementia (Sidransky et al., 2009, NEng J Med, 361: 1651-1661; Tsuang et al., 2012, Neurology, 79: 1944-1950). Cyclohexene tetraol β-epoxide (CBE) is an irreversible inhibitor of glucocerebrosidase and is used to generate in vitro and in vivo models for studying Gaucher disease and Parkinson's disease. Systemic inhibition of lysosomal glucocerebrosidase using cyclohexene tetraol-β-epoxide (CBE) has been associated with specific Parkinson's disease-related pathologies, including accumulation of α-synuclein aggregates, elevated glycosphingolipids, and widespread neuroinflammation (Rocha et al., 2015, Antioxid Redox Signal, 23:550-564).

[0137] Parkinson's disease is a progressive disorder that affects movement and is recognized as the second most common neurodegenerative disease after Alzheimer's disease. Common symptoms of Parkinson's disease include resting tremor, rigidity, and bradykinesia, and non-motor symptoms such as depression, constipation, pain, sleep disorders, genitourinary problems, cognitive decline, and olfactory dysfunction are also increasingly associated with the disease. Key Features

[0138] Recent studies have shown that mutations in the glucocerebrosidase gene are associated with an increased risk of Parkinson's disease, with more severe mutations conferring a higher risk. It has been reported that glucocerebrosidase activity is reduced in the substantia nigra, cerebellum, and caudate nucleus of Parkinson's patients (Alcalay et al., 2015, Brain 138:2648).

[0139] Mutations in glucocerebrosidase can lead to increased toxicity and / or altered cellular function due to diversion of cellular resources (Gregg et al., 2012, Ann. Neurol. 72:455-46; Schondorf et al., 2014, Nat. Commun. 5:4028; Kilpatrick et al., 2016, Cell Calcium. 59:12-20; Cullen et al., 2011, Ann. Neurol. 69:940-953). Studies in rodent models of Parkinson's disease also suggest a link between glucocerebrosidase activity and α-synuclein accumulation (Rocha et al., 2015, Antioxidants & Redox Signaling 23:550; Rocha et al., 2015, Neurobiology of Disease 82:495).

[0140] Increased expression of GPNMB in the brain has been detected in many different neurodegenerative disorders including Parkinson's disease, Alzheimer's disease and ALS (Huttenrauch et al., 2018, Acta Neuropathol Commun, 6:108; Tanaka et al., 2012, Sci Rep, 2:573; Ono et al., 2016, Sci Rep, 6:23241; Moloney et al., 2018, Neurobiol Dis, 120:1-11). GPNMB levels are elevated in the substantia nigra of patients with sporadic Parkinson's disease (Moloney et al., 2018, Neurobiol Dis, 120:1-11). In addition, the single nucleotide polymorphism (SNP) rs199347, a known leading risk SNP for Parkinson's disease, is located in the GPNMB gene and leads to increased GPNMB expression (Murthy et al., 2017, Neurogenetics, 18:121-133).

[0141] The present disclosure demonstrates that using anti-GNPMB antibodies to reduce GPNMB activity or expression results in increased glucocerebrosidase activity.

[0142] GPNMB and cancer

[0143] GPNMB expression and function are associated with cancer. GPNMB was first identified as a gene differentially expressed in melanoma cell lines with high and low metastatic potential (Weterman et al., 1995, Int J Cancer, 60:73-81; Tse et al., 2006, Clin Cancer Res, 12:1373-1382; Kuan et al., 2006, Clinical Cancer Research, 12:1970-1982; Rose et al., 2007, Molecular Cancer Research, 5:1001-1014). GPNMB expression has also been described in liver cancer, squamous cell lung cancer, and soft tissue tumors (Onaga et al., 2003, J Hepatol, 39:779-785; Borczuk et al., 2003, Am J Pathol, 163:1949-1960; Nielsen et al., 2002, Lancet, 359:1301-1307). Ectopic expression of GPNMB in cancer cells increases their invasiveness in vitro and promotes their metastasis in vivo (Onaga et al., 2003, J Hepatol, 39:779-785; Rich and Shi, 2003, J Biol Chem, 278:15951-15957).

[0144] GPNMB is highly expressed in a variety of tumor types, including triple-negative breast cancer, uveal and skin melanoma, glioblastoma, hepatocellular carcinoma, prostate cancer, osteosarcoma, lung cancer, bladder cancer and lymphangioleiomyomatosis (Taya and Hammes, 2018, Steroids, 133: 102-107). It has been shown that GPNMB promotes the migration, invasion and metastasis of tumor cells. GPNMB can inhibit the inflammatory response around cancer cell growth, thus playing a role in driving tumor progression (Maric et al., 2013, Onc Targets Therapy, 6: 839-852).

[0145] An antibody against GPNMB (named glembatumumab vedotin) was evaluated in Phase I / II clinical trials as a treatment for advanced breast cancer and melanoma; however, these clinical trials were terminated in 2018 due to the failure of the candidate drug to improve survival and prevent tumor progression (Saade et al., 2021, Frontiers in Immunol, 12:674739). The present disclosure shows that using anti-GNPMB antibodies to reduce GPNMB activity or expression reduces tumor growth in mouse tumor models.

[0146] Exemplary Anti-GPNMB Antibody and Certain Other Antibody Embodiments

[0147] In some aspects, provided herein are anti-GPNMB antibodies comprising at least one, two, three, four, five, or six HVRs selected from: (a) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77; (b) an HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, and 78; (c) an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: NO:7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 and 79; (d) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152 and 155; (e) an HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:83, 86, 89, 92, ID NO: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153 and 156; and (f) an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154 and 157.

[0148] In some aspects, provided herein are compositions comprising at least one, at least two, or all three of the following V H45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, and 78; (c) an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: SEQ ID NO: NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 and 79.

[0149] In some aspects, provided herein are compositions comprising at least one, at least two, or all three of the following V L Anti-GPNMB antibodies of HVR sequences: (a) HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, and 155; (b) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: NO:84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153 and 156; and (c) an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154 and 157.

[0150] In some aspects, provided herein are anti-GPNMB antibodies comprising: (a) V H A domain comprising at least one, at least two or all three V HHVR sequences: (i) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77; (ii) an HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, and 78; and (iii) an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 and 79; and (b) V L A domain comprising at least one, at least two or all three V L HVR sequences: (i) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, and 155; (ii) an HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: NO: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, and 156; and (iii) an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, and 157.

[0151] In some aspects, provided herein are anti-GPNMB antibodies comprising: (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 7; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 83; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 84; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85; (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 8; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 9; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 86; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 87; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: NO:88; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:11; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:12; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:13; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:89; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:90; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:91; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:14; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:15; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:16; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:92; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:93; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: NO:94; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:17; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:18; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:19; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:95; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:96; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:97; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:20;(b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 21; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 22; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 98; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 99; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 24; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 102; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 24; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25; NO:26; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:27; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:28; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:104; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:105; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:106; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:29; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:31; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:107; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:108; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: NO:109; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:32; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:33; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:34; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:110; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:111; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:112; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:35; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:36;(c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 113; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 115; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 38; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 39; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 40; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 116; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 118; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 41; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 39; NO:42; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:43; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:119; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:120; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:121; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:44; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:45; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:46; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:122; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:123; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:124; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:44; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:45; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:46; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:122; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:123; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:124 NO:47; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:48; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:49; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:125; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:126; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:127; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:50; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:51; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:52;(d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 128; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 129; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 130; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 53; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 54; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 131; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 132; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 56; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 57; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: NO:58; (d) HVR-H3 comprising the amino acid sequence of SEQ ID NO:134; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:135; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:136; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:59; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:60; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:61; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:137; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:138; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:139; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:62; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:60; NO:63; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:64; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:140; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:141; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:142; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:65; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:66; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:67; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:143;(e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 144; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 145; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 68; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 69; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 70; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 146; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 147; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 148; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 146; NO:149; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:150; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:151; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:74; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:75; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:76; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:152; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:153; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:154; and (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:77; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:78; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:76 (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 155; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 156; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 157.

[0152] In another aspect, the anti-GPNMB antibody comprises a heavy chain variable domain (V H) sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207 and 209. In certain aspects, a V sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207 and 209. H The sequence contains substitutions (e.g., conservative substitutions), insertions or deletions relative to the reference sequence, but the anti-GPNMB antibodies comprising the sequence retain the ability to bind to GPNMB. In some aspects, in SEQ ID NO:161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207 and 209, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some aspects, substitutions, insertions or deletions occur in regions outside HVR (i.e., in FR). Optionally, the anti-GPNMB antibody comprises V sequences of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, and 209. H Sequence, including post-translational modifications of said sequence. In a specific aspect, V Hcomprising one, two or three HVRs selected from the group consisting of: (a) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, and 77; (b) an HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, and 78; and (c) an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76 and 79.

[0153] In another aspect, an anti-GPNMB antibody is provided, wherein the antibody comprises a light chain variable domain (V L ), which has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208 and 210. In some aspects, a V sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208 and 210. LThe sequence contains substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but anti-GPNMB antibodies comprising the sequence retain the ability to bind to GPNMB. In some aspects, in SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, or 210, a total of 1 to 10 amino acids are substituted, inserted, and / or deleted. In certain aspects, a total of 1 to 5 amino acids are substituted, inserted, and / or deleted in SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, or 210. In certain aspects, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti-GPNMB antibody comprises a V sequence of SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, or 210. L Sequence, including post-translational modifications of said sequence. In a specific aspect, V L comprising one, two or three HVRs selected from the group consisting of: (a) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, and 155; (b) an HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, and 155; NO: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, and 156; and (c) an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, and 157.

[0154] In some aspects, an anti-GPNMB antibody is provided, wherein the antibody comprises a V as in any of the aspects provided above. H and V as in any of the aspects provided above L In some aspects, provided herein are anti-GPNMB antibodies, wherein the antibody comprises a V as in any of the aspects provided above. H and V as in any of the aspects provided above L In one aspect, the antibody comprises the V sequences in SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, and 209, and SEQ ID NOs: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, and 210, respectively. H and V L sequences, including post-translational modifications of those sequences.

[0155] In some aspects, provided herein are sequences comprising a heavy chain variable domain (V H ) and light chain variable domain (V L ) of anti-GPNMB antibodies, wherein V H and V L Selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO: 161 H and V comprising the amino acid sequence of SEQ ID NO: 162 L ; V comprising the amino acid sequence of SEQ ID NO: 163 H and V comprising the amino acid sequence of SEQ ID NO: 164 L ; V comprising the amino acid sequence of SEQ ID NO: 165 H and V comprising the amino acid sequence of SEQ ID NO: 166 L ; V comprising the amino acid sequence of SEQ ID NO: 167 H and V comprising the amino acid sequence of SEQ ID NO: 168 L ; V comprising the amino acid sequence of SEQ ID NO: 169 H and V comprising the amino acid sequence of SEQ ID NO: 170 L ; V comprising the amino acid sequence of SEQ ID NO: 171 Hand V comprising the amino acid sequence of SEQ ID NO: 172 L ; V comprising the amino acid sequence of SEQ ID NO: 173 H and V comprising the amino acid sequence of SEQ ID NO: 174 L ; V comprising the amino acid sequence of SEQ ID NO: 175 H and V comprising the amino acid sequence of SEQ ID NO: 176 L ; V comprising the amino acid sequence of SEQ ID NO: 177 H and V comprising the amino acid sequence of SEQ ID NO: 178 L ; V comprising the amino acid sequence of SEQ ID NO: 179 H and V comprising the amino acid sequence of SEQ ID NO: 180 L ; V comprising the amino acid sequence of SEQ ID NO: 181 H and V comprising the amino acid sequence of SEQ ID NO: 182 L ; V comprising the amino acid sequence of SEQ ID NO: 183 H and V comprising the amino acid sequence of SEQ ID NO: 184 L ; V comprising the amino acid sequence of SEQ ID NO: 185 H and V comprising the amino acid sequence of SEQ ID NO: 186 L ; V comprising the amino acid sequence of SEQ ID NO: 187 H and V comprising the amino acid sequence of SEQ ID NO: 188 L ; V comprising the amino acid sequence of SEQ ID NO: 189 H and V comprising the amino acid sequence of SEQ ID NO: 190 L ; V comprising the amino acid sequence of SEQ ID NO: 191 H and V comprising the amino acid sequence of SEQ ID NO: 192 L ; V comprising the amino acid sequence of SEQ ID NO: 193 H and V comprising the amino acid sequence of SEQ ID NO: 194 L ; V comprising the amino acid sequence of SEQ ID NO: 195 H and V comprising the amino acid sequence of SEQ ID NO: 196 L ; V comprising the amino acid sequence of SEQ ID NO: 197 H and V comprising the amino acid sequence of SEQ ID NO: 198 L; V comprising the amino acid sequence of SEQ ID NO: 199 H and V comprising the amino acid sequence of SEQ ID NO: 200 L ; V comprising the amino acid sequence of SEQ ID NO: 201 H and V comprising the amino acid sequence of SEQ ID NO: 202 L ; V comprising the amino acid sequence of SEQ ID NO: 203 H and V comprising the amino acid sequence of SEQ ID NO: 204 L ; V comprising the amino acid sequence of SEQ ID NO: 205 H and V comprising the amino acid sequence of SEQ ID NO: 206 L ; V comprising the amino acid sequence of SEQ ID NO: 207 H and V comprising the amino acid sequence of SEQ ID NO: 208 L and V comprising the amino acid sequence of SEQ ID NO: 209 H and V comprising the amino acid sequence of SEQ ID NO: 210 L .

[0156] In some aspects, the anti-GPNMB antibodies of the present disclosure competitively inhibit binding of at least one reference antibody selected from the group consisting of anti-GPNMB antibodies GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, and GPN-65, and any combination thereof, to GPNMB.

[0157] In some aspects, the anti-GPNMB antibodies of the present disclosure bind to an epitope of human GPNMB that is the same as or overlaps with an epitope of GPNMB bound by at least one reference antibody selected from the group consisting of anti-GPNMB antibodies GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, and GPN-65. Detailed exemplary methods for mapping epitopes bound by antibodies are provided in Morris (1996) "Epitope Mapping Protocols", Methods in Molecular Biology Vol. 66 (Humana Press, Totowa, NJ).

[0158] In some aspects, the anti-GPNMB antibodies of the present disclosure competitively inhibit the binding of at least one reference antibody, or bind to an epitope of human GPNMB that is identical to or overlaps with an epitope of GPNMB bound by at least one reference antibody, wherein the reference antibody is a heavy chain variable domain (V H ) and light chain variable domain (V L ) of anti-GPNMB antibodies, wherein V H and V L Selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO: 161 H and V comprising the amino acid sequence of SEQ ID NO: 162 L ; V comprising the amino acid sequence of SEQ ID NO: 163 H and V comprising the amino acid sequence of SEQ ID NO: 164 L ; V comprising the amino acid sequence of SEQ ID NO: 165 H and V comprising the amino acid sequence of SEQ ID NO: 166 L ; V comprising the amino acid sequence of SEQ ID NO: 167 H and V comprising the amino acid sequence of SEQ ID NO: 168 L ; V comprising the amino acid sequence of SEQ ID NO: 169 H and V comprising the amino acid sequence of SEQ ID NO: 170 L ; V comprising the amino acid sequence of SEQ ID NO: 171 Hand V comprising the amino acid sequence of SEQ ID NO: 172 L ; V comprising the amino acid sequence of SEQ ID NO: 173 H and V comprising the amino acid sequence of SEQ ID NO: 174 L ; V comprising the amino acid sequence of SEQ ID NO: 175 H and V comprising the amino acid sequence of SEQ ID NO: 176 L ; V comprising the amino acid sequence of SEQ ID NO: 177 H and V comprising the amino acid sequence of SEQ ID NO: 178 L ; V comprising the amino acid sequence of SEQ ID NO: 179 H and V comprising the amino acid sequence of SEQ ID NO: 180 L ; V comprising the amino acid sequence of SEQ ID NO: 181 H and V comprising the amino acid sequence of SEQ ID NO: 182 L ; V comprising the amino acid sequence of SEQ ID NO: 183 H and V comprising the amino acid sequence of SEQ ID NO: 184 L ; V comprising the amino acid sequence of SEQ ID NO: 185 H and V comprising the amino acid sequence of SEQ ID NO: 186 L ; V comprising the amino acid sequence of SEQ ID NO: 187 H and V comprising the amino acid sequence of SEQ ID NO: 188 L ; V comprising the amino acid sequence of SEQ ID NO: 189 H and V comprising the amino acid sequence of SEQ ID NO: 190 L ; V comprising the amino acid sequence of SEQ ID NO: 191 H and V comprising the amino acid sequence of SEQ ID NO: 192 L ; V comprising the amino acid sequence of SEQ ID NO: 193 H and V comprising the amino acid sequence of SEQ ID NO: 194 L ; V comprising the amino acid sequence of SEQ ID NO: 195 H and V comprising the amino acid sequence of SEQ ID NO: 196 L ; V comprising the amino acid sequence of SEQ ID NO: 197 H and V comprising the amino acid sequence of SEQ ID NO: 198 L; V comprising the amino acid sequence of SEQ ID NO: 199 H and V comprising the amino acid sequence of SEQ ID NO: 200 L ; V comprising the amino acid sequence of SEQ ID NO: 201 H and V comprising the amino acid sequence of SEQ ID NO: 202 L ; V comprising the amino acid sequence of SEQ ID NO: 203 H and V comprising the amino acid sequence of SEQ ID NO: 204 L ; V comprising the amino acid sequence of SEQ ID NO: 205 H and V comprising the amino acid sequence of SEQ ID NO: 206 L ; V comprising the amino acid sequence of SEQ ID NO: 207 H and V comprising the amino acid sequence of SEQ ID NO: 208 L and V comprising the amino acid sequence of SEQ ID NO: 209 H and V comprising the amino acid sequence of SEQ ID NO: 210 L .

[0159] In some aspects, provided herein are anti-GPNMB antibodies comprising at least one, two, three, four, five, or six HVRs selected from the group consisting of: (a) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71 and 23; (b) an HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 255, 256, 257, 258, 259, and 260; (c) an HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 73, 261, 19, and 262; (d) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 263, 264, 265, 266, 267, and 268; (e) an HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: NO: 269, 270, 271, 272, 273, 96, 274, 275, 276 and 277; and (f) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 151, 278, 279, 280, 97 and 281.

[0160] In some aspects, provided herein are anti-GPNMB antibodies comprising at least one, at least two, or all three V selected from the group consisting of HHVR sequences: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71 and 23; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 255, 256, 257, 258, 259 and 260; (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 73, 261, 19 and 262.

[0161] In some aspects, provided herein are anti-GPNMB antibodies comprising at least one, at least two, or all three V selected from the group consisting of L HVR sequences: (a) HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 263, 264, 265, 266, 267 and 268; (b) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 269, 270, 271, 272, 273, 96, 274, 275, 276 and 277; and (c) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 269, 270, 271, 272, 273, 96, 274, 275, 276 and 277.

[0162] In some aspects, provided herein are anti-GPNMB antibodies comprising (a) V H A domain comprising at least one, at least two or all three V H HVR sequences: (i) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71 and 23; (ii) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 255, 256, 257, 258, 259 and 260; and (iii) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 73, 261, 19 and 262; and (b) V L A domain comprising at least one, at least two or all three V L HVR sequences: (i) HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 263, 264, 265, 266, 267 and 268; (ii) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 263, 264, 265, 266, 267 and 268; and (iii) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 151, 278, 279, 280, 97 and 281.

[0163] In some aspects, provided he...

Claims

1. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody antagonizes GPNMB activity.

2. The anti-GPNMB antibody of claim 1, wherein the anti-GPNMB antibody modulates the expression of activation surface markers on myeloid cells.

3. The anti-GPNMB antibody of claim 1 or 2, wherein the anti-GPNMB antibody increases cell surface expression of PD-L1 in human macrophages. 4 . The anti-GPNMB antibody of any one of claims 1 to 3 , wherein the anti-GPNMB antibody increases the cell surface expression of CD40 in human macrophages. 5 . The anti-GPNMB antibody of any one of claims 1 to 4 , wherein the anti-GPNMB antibody increases the cell surface expression of CD80 in human macrophages.

6. The anti-GPNMB antibody of any one of claims 1 to 5, wherein the anti-GPNMB antibody modulates lysosomal function in myeloid cells. 7 . The anti-GPNMB antibody of any one of claims 1 to 6 , wherein the anti-GPNMB antibody increases glucocerebrosidase activity in human macrophages.

8. The anti-GPNMB antibody of any one of claims 1 to 7, wherein the anti-GPNMB antibody reduces cell surface expression of GPNMB in human macrophages.

9. The anti-GPNMB antibody of any one of claims 1 to 8, wherein the anti-GPNMB antibody alters the interferon pathway gene expression pattern in human macrophages.

10. The anti-GPNMB antibody of any one of claims 1 to 9, wherein the anti-GPNMB antibody reduces tumor volume in a mouse tumor model, such as the MC38 model.

11. The anti-GPNMB antibody of any one of claims 1 to 10, wherein the anti-GPNMB antibody reduces tumor growth rate in a murine tumor model, such as the MC38 model.

12. The anti-GPNMB antibody of any one of claims 1 to 11, wherein the anti-GPNMB antibody increases the level of IL-12p40 in serum.

13. The anti-GPNMB antibody of any one of claims 1 to 12, wherein the anti-GPNMB antibody increases the level of CCL5 in serum. 14 . The anti-GPNMB antibody of any one of claims 1 to 13 , wherein the anti-GPNMB antibody is a GPNMB ligand blocking antibody.

15. The anti-GPNMB antibody of any one of claims 1 to 13, wherein the anti-GPNMB antibody is a non-blocking antibody.

16. The anti-GPNMB antibody of any one of claims 1 to 13, wherein the anti-GPNMB antibody antagonizes GPNMB activity independent of ligand blocking activity.

17. The anti-GPNMB antibody of any one of claims 1 to 16, wherein the anti-GPNMB antibody antagonizes GPNMB activity in vivo.

18. The anti-GPNMB antibody of any one of claims 1 to 17, wherein the anti-GPNMB antibody binds to GPNMB expressed on the surface of a cell.

19. The anti-GPNMB antibody of any one of claims 1 to 18, wherein the anti-GPNMB antibody promotes macrophage activation.

20. The anti-GPNMB antibody of any one of claims 1 to 19, wherein the anti-GPNMB antibody overcomes the reduction in glucocerebrosidase activity associated with reduced progranulin levels.

21. The anti-GPNMB antibody of any one of claims 1 to 20, wherein the anti-GPNMB antibody reduces the expression level of GPNMB in a cell, optionally a macrophage.

22. The anti-GPNMB antibody of any one of claims 1 to 21, wherein the anti-GPNMB antibody reduces the expression level of LAMP2 in a cell, optionally a macrophage, a monocyte, or a neutrophil.

23. The anti-GPNMB antibody of any one of claims 1 to 22, wherein the anti-GPNMB antibody inhibits or reduces inflammasome activation.

24. The anti-GPNMB antibody of any one of claims 1 to 23, wherein the anti-GPNMB antibody inhibits IL-1β expression or release.

25. The anti-GPNMB antibody of any one of claims 1 to 24, wherein the anti-GPNMB antibody reduces neuroinflammation.

26. The anti-GPNMB antibody of any one of claims 1 to 25, wherein the anti-GPNMB antibody reduces the expression of C1q, GFAP, IBA1, and CTSD associated with neuroinflammation.

27. The anti-GPNMB antibody of any one of claims 1 to 26, wherein the anti-GPNMB antibody reduces lysosomal stress.

28. The anti-GPNMB antibody of any one of claims 1 to 27, wherein the anti-GPNMB antibody binds to a polypeptide selected from the group consisting of GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-44, GPN-45, GPN-46, GPN-47, GPN-48, GPN-49, GPN-50, GPN-51, GPN-52, GPN-53, GPN-54, GPN-55, GPN-56, GPN-57, GPN-58, GPN-59, GPN-60, GPN-61, GPN-62, GPN-63, GPN-64, GPN-65 One or more antibodies of PN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97, GPN-98, and any combination thereof compete for binding to GPNMB.

29. The anti-GPNMB antibody of any one of claims 1 to 28, wherein the anti-GPNMB antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain, the heavy chain variable domain, or both comprise at least one, at least two, at least three, at least four, at least five, or six HVRs selected from HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3 of an antibody selected from: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-30, GPN-31, GPN-32, GPN-33, GPN-34, GPN-35, GPN-36, GPN-37, GPN-38, GPN-39, GPN-40, GPN-41, GPN-42, GPN-43, GPN-44, GPN-45, GPN-46, GPN-47, GPN-48, GPN-49, GPN-50, GPN-51, GPN-52, GPN-53, GPN-54, GPN-55, GPN-56, GPN-57, GPN-58, GPN-59, GPN-60, GPN-61, GPN-62, GPN-63, GPN-64, GPN-65 N-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, G PN-82, GPN-83, ​​GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98.

30. The anti-GPNMB antibody of claim 29, wherein: a. the HVR-H1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74 and 77; b. the HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 255, 256, 257, 258, 259, and 260; c. the HVR-H3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76, 79, 261, and 262; d. the HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 263, 264, 265, 266, 267, and 268; e. the HVR-L2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, 156, 269, 270, 271, 272, 273, 274, 275, 276, and 277; and / or f. the HVR-L3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, 157, 278, 279, 280 and 281.

31. The anti-GPNMB antibody of claim 29 or 30, wherein: a. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:5, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:6, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:7, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:83, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:84, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:85; or b. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 8, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 9, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 10, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 86, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 87, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 88; or c. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 11, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 12, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 13, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 89, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 90, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 91; or d. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 14, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 15, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 16, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 92, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 93, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 94; or e. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 17, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 18, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 19, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 95, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 96, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 97; or f. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:20, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:21, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:22, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:98, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:99, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:100; or g. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 24, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 25, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 102, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 103; or h. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:26, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:27, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:28, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:104, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:105, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:106; or i. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 29, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 30, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 31, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 107, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 108, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 109; or j. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:32, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:33, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:34, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:110, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:111, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:112; or k. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:35, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:36, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:37, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:113, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:114, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:115; or 1. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:38, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:39, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:40, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:116, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:117, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:118; or m. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:41, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:42, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:43, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:119, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:120, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:121; or n. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:44, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:45, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:46, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:122, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:123, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:124; or o. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:47, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:48, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:49, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:125, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:126, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:127; or p. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:50, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:51, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:52, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:128, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:129, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:130; or q. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:53, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:54, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:55, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:131, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:132, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:133; or r. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:56, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:57, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:58, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:134, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:135, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:136; or s. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:59, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:60, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:61, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:137, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:138, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:139; or t. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:62, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:63, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:64, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:140, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:141, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:142; or u. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:65, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:66, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:67, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:143, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:144, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:145; or v. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:68, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:69, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:70, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:146, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:147, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:148; or w. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:72, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:149, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:150, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:151; or x. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:74, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:75, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:76, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:152, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:153, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:154; or y. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 77, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 78, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 79, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 155, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 156, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 157; or z. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:255, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:263, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:269, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:151; or aa. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:256, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:270, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or bb. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:265, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:271, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or cc. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:261, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:265, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:271, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or dd. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:258, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:266, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:272, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or ee. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 273, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or ff. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:261, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:273, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or gg. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:272, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:279; or hh. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:261, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:272, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:278; or ii. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 258, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 272, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 278; or jj. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:71, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:257, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:73, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:264, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:272, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:280; or kk. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:259, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:19, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:267, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:96, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:97; or 11. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:268, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:274, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:281; or mm. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:268, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:274, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:97; or nn. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:268, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:275, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:281; or oo. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:267, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:276, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:97; or pp. the HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:268, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:277, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:97; or qq. The HVR-H1 comprises the amino acid sequence of SEQ ID NO:23, the HVR-H2 comprises the amino acid sequence of SEQ ID NO:260, the HVR-H3 comprises the amino acid sequence of SEQ ID NO:262, the HVR-L1 comprises the amino acid sequence of SEQ ID NO:267, the HVR-L2 comprises the amino acid sequence of SEQ ID NO:96, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:

97.

32. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region (VH) comprises: a. HVR-H1 comprising an amino acid sequence selected from any one of the following: SEQ ID NO: 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74 and 77; b. an HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NO: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 255, 256, 257, 258, 259, and 260; and c. an HVR-H3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 73, 76, 79, 261, and 262.

33. The antibody of claim 32, wherein the light chain variable region (VL) comprises: a. an HVR-L1 comprising an amino acid sequence selected from any one of the following: SEQ ID NO: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 263, 264, 265, 266, 267, and 268; b. an HVR-L2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, 156, 269, 270, 271, 272, 273, 274, 275, 276, and 277; and c. an HVR-L3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 85, 88, 91, 94, 97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, 142, 145, 148, 151, 154, 157, 278, 279, 280, and 281.

34. The antibody of claim 32 or 33, wherein the antibody comprises a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239 and 240.

35. The antibody of any one of claims 32 to 34, wherein the antibody comprises a VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 and 254.

36. The antibody of any one of claims 32 to 35, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to the amino acid sequence of any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239 and 240.

37. The antibody of any one of claims 32 to 36, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to the amino acid sequence of any one of SEQ ID NOs: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 and 254.

38. The antibody of any one of claims 32 to 37, wherein the antibody comprises a VH comprising an amino acid sequence selected from any one of SEQ ID NOs: 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 234, 235, 236, 237, 238, 239, and 240.

39. The antibody of any one of claims 32 to 38, wherein the antibody comprises a VL comprising an amino acid sequence selected from any one of SEQ ID NOs: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, and 254.

40. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises: a. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:5, HVR-H2 comprising the amino acid sequence of SEQ ID NO:6, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:7; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:83, HVR-L2 comprising the amino acid sequence of SEQ ID NO:84, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:85; b. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 8, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 9, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 86, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 87, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 88; c. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 12, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 13; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 89, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 90, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91 d. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 14, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 15, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 16; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 92, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 93, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 94; e. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 17, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 18, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 19; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 95, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; f. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:20, HVR-H2 comprising the amino acid sequence of SEQ ID NO:21, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:22; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:98, HVR-L2 comprising the amino acid sequence of SEQ ID NO:99, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:100; g. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:24, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:25; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:101, HVR-L2 comprising the amino acid sequence of SEQ ID NO:102, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:103; h. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:26, HVR-H2 comprising the amino acid sequence of SEQ ID NO:27, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:28; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:104, HVR-L2 comprising the amino acid sequence of SEQ ID NO:105, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:106; i. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:29, HVR-H2 comprising the amino acid sequence of SEQ ID NO:30, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:31; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:107, HVR-L2 comprising the amino acid sequence of SEQ ID NO:108, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:109; j. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:32, HVR-H2 comprising the amino acid sequence of SEQ ID NO:33, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:34; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:110, HVR-L2 comprising the amino acid sequence of SEQ ID NO:111, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:112; k. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:35, HVR-H2 comprising the amino acid sequence of SEQ ID NO:36, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:37; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:113, HVR-L2 comprising the amino acid sequence of SEQ ID NO:114, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:115; 1. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:38, HVR-H2 comprising the amino acid sequence of SEQ ID NO:39, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:40; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:116, HVR-L2 comprising the amino acid sequence of SEQ ID NO:117, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:118; m. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:41, HVR-H2 comprising the amino acid sequence of SEQ ID NO:42, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:43; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:119, HVR-L2 comprising the amino acid sequence of SEQ ID NO:120, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:121; n. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:44, HVR-H2 comprising the amino acid sequence of SEQ ID NO:45, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:46; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:122, HVR-L2 comprising the amino acid sequence of SEQ ID NO:123, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:124; o. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:47, HVR-H2 comprising the amino acid sequence of SEQ ID NO:48, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:49; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:125, HVR-L2 comprising the amino acid sequence of SEQ ID NO:126, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:127; p.VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:50, HVR-H2 comprising the amino acid sequence of SEQ ID NO:51, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:52; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:128, HVR-L2 comprising the amino acid sequence of SEQ ID NO:129, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:130; q. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:53, HVR-H2 comprising the amino acid sequence of SEQ ID NO:54, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:55; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:131, HVR-L2 comprising the amino acid sequence of SEQ ID NO:132, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:133; r. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:56, HVR-H2 comprising the amino acid sequence of SEQ ID NO:57, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:58; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:134, HVR-L2 comprising the amino acid sequence of SEQ ID NO:135, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:136; s. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:59, HVR-H2 comprising the amino acid sequence of SEQ ID NO:60, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:61; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:137, HVR-L2 comprising the amino acid sequence of SEQ ID NO:138, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:139; t. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:62, HVR-H2 comprising the amino acid sequence of SEQ ID NO:63, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:64; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:140, HVR-L2 comprising the amino acid sequence of SEQ ID NO:141, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:142; u. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:65, HVR-H2 comprising the amino acid sequence of SEQ ID NO:66, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:67; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:143, HVR-L2 comprising the amino acid sequence of SEQ ID NO:144, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:145; v. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:68, HVR-H2 comprising the amino acid sequence of SEQ ID NO:69, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:70; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:146, HVR-L2 comprising the amino acid sequence of SEQ ID NO:147, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:148; w. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:72, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:73; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:149, HVR-L2 comprising the amino acid sequence of SEQ ID NO:150, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:151; x. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:74, HVR-H2 comprising the amino acid sequence of SEQ ID NO:75, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:76; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:152, HVR-L2 comprising the amino acid sequence of SEQ ID NO:153, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:154; y. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:77, HVR-H2 comprising the amino acid sequence of SEQ ID NO:78, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:79; and VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:155, HVR-L2 comprising the amino acid sequence of SEQ ID NO:156, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:157; z. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 255, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 263, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 269, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 151; aa.VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:256, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:73; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:264, HVR-L2 comprising the amino acid sequence of SEQ ID NO:270, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:278; bb. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:265, HVR-L2 comprising the amino acid sequence of SEQ ID NO:271, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:278; cc. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 265, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 271, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; dd. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:258, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:266, HVR-L2 comprising the amino acid sequence of SEQ ID NO:272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:278; ee. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 273, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; ff. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:261; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:264, HVR-L2 comprising the amino acid sequence of SEQ ID NO:273, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:278; gg. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 279; hh.VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:71, HVR-H2 comprising the amino acid sequence of SEQ ID NO:257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:261; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:264, HVR-L2 comprising the amino acid sequence of SEQ ID NO:272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:278; ii. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 258, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; jj. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 280; kk.VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:259, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:19; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:267, HVR-L2 comprising the amino acid sequence of SEQ ID NO:96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:97; 11. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:262; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:268, HVR-L2 comprising the amino acid sequence of SEQ ID NO:274, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:281; mm.VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:262; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:268, HVR-L2 comprising the amino acid sequence of SEQ ID NO:274, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:97; nn. VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 275, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 281; oo.VH, comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:262; VL, comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:267, HVR-L2 comprising the amino acid sequence of SEQ ID NO:276, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:97; pp. VH comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:262; VL comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:268, HVR-L2 comprising the amino acid sequence of SEQ ID NO:277, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:97; or qq.VH, which comprises HVR-H1 comprising the amino acid sequence of SEQ ID NO:23, HVR-H2 comprising the amino acid sequence of SEQ ID NO:260, and HVR-H3 comprising the amino acid sequence of SEQ ID NO:262; VL, which comprises HVR-L1 comprising the amino acid sequence of SEQ ID NO:267, HVR-L2 comprising the amino acid sequence of SEQ ID NO:96, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

97.

41. The antibody of claim 40, wherein the antibody comprises: a. The HVR of claim 40.a. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 161; b. The HVR of claim 40.b. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 163; c. The HVR of claim 40.c. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 165; d. The HVR of claim 40.d. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 167; e. The HVR of claim 40.e. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 169; f. The HVR of claim 40.f. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 171; g. The HVR of claim 40.g. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 173; h. The HVR of claim 40.h. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 175; i. The HVR of claim 40.i. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 177; j. The HVR of claim 40.j. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 179; k. The HVR of claim 40.k. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 181; 1. The HVR of claim 40.

1. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 183; m. The HVR of claim 40.m. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 185; n. The HVR of claim 40.n. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 187 o. The HVR of claim 40.o. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; p. The HVR of claim 40.p. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191; q. The HVR of claim 40.q. and further comprising a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 193; r. The HVR of claim 40.r. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 195; s. The HVR of claim 40.s. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 197; t. The HVR of claim 40.t. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 199; u. The HVR of claim 40.u. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 201; v. The HVR of claim 40.v. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 203; w. The HVR of claim 40.w. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 205; x. The HVR of claim 40.x. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 207; y. The HVR of claim 40.y. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 209; z. The HVR of claim 40.z. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 234; aa. The HVR of claim 40.aa. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 235; bb. The HVR of claim 40.bb. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; cc. The HVR of claim 40.cc. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; dd. The HVR of claim 40.dd. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 238; ee. The HVR of claim 40.ee. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; ff. The HVR of claim 40.ff. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; gg. The HVR of claim 40.gg. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; hh. The HVR of claim 40.hh. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; ii. The HVR of claim 40.ii. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 238; jj. The HVR of claim 40.jj. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 236; kk. The HVR of claim 40.kk. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 239; 11. The HVR of claim 40.

11. and further comprising a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; mm. The HVR of claim 40. mm. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; nn. The HVR of claim 40.nn. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; oo. The HVR of claim 40.oo. and further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; pp. The HVR of claim 40. pp. and further comprising a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 240; or qq. The HVR of claim 40.qq. and further comprising a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:

240.

42. The antibody of claim 40 or 41, wherein the antibody comprises: a. The HVR of claim 40.a. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; b. The HVR of claim 40.b. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; c. The HVR of claim 40.c. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; d. The HVR of claim 40.d. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 168; e. The HVR of claim 40.e. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170; f. The HVR of claim 40.f. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172; g. The HVR of claim 40.g. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 174; h. The HVR of claim 40.h. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 176; i. The HVR of claim 40.i. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 178; j. The HVR of claim 40.j. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 180; k. The HVR of claim 40.k. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 182; 1. The HVR of claim 40.

1. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 184; m. The HVR of claim 40.m. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 186; n. The HVR of claim 40.n. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 188; o. The HVR of claim 40.o. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190; p. The HVR of claim 40.p. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192; q. The HVR of claim 40.q. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194; r. The HVR of claim 40.r. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 196; s. The HVR of claim 40.s. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 198; t. The HVR of claim 40.t. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 200; u. The HVR of claim 40.u. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 202; v. The HVR of claim 40.v. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 204; w. The HVR of claim 40.w. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 206; x. The HVR of claim 40.x. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 208; y. The HVR of claim 40.y. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 210 z. The HVR of claim 40.z. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 241; aa. The HVR of claim 40.aa. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 242; bb. The HVR of claim 40.bb. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 243; cc. The HVR of claim 40.cc. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 243; dd. The HVR of claim 40.dd. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 244; ee. The HVR of claim 40.ee. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 245; ff. The HVR of claim 40.ff. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 245; gg. The HVR of claim 40.gg. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 246; hh. The HVR of claim 40.hh. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 247; ii. The HVR of claim 40.ii. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 247; jj. The HVR of claim 40.jj. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 248; kk. The HVR of claim 40.kk. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 249; 11. The HVR of claim 40.

11. and further comprising a VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 250; mm. The HVR of claim 40. mm. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 251; nn. The HVR of claim 40.nn. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 252; oo. The HVR of claim 40.oo. and further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 253; pp. The HVR of claim 40. pp. and further comprising a VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 254; or qq. The HVR of claim 40.qq. and further comprising a VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:

249.

43. The antibody of any one of claims 40 to 42, wherein the antibody comprises: a. The HVR of claim 40.a. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 161; b. The HVR of claim 40.b. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 163; c. The HVR of claim 40.c. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 165; d. The HVR of claim 40.d. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 167; e. The HVR of claim 40.e. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 169; f. The HVR of claim 40.f. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 171; g. The HVR of claim 40.g. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 173; h. The HVR of claim 40.h. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 175; i. The HVR of claim 40.i. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 177; j. The HVR of claim 40.j. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 179; k. The HVR of claim 40.k. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 181; 1. The HVR of claim 40.

1. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 183; m. The HVR of claim 40.m. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 185; n. The HVR of claim 40.n. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 187; o. The HVR of claim 40.o. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 189; p. The HVR of claim 40.p. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 191; q. The HVR of claim 40.q. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 193; r. The HVR of claim 40.r. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 195; s. The HVR of claim 40.s. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 197; t. The HVR of claim 40.t. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 199; u. The HVR of claim 40.u. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 201; v. The HVR of claim 40.v. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 203; w. The HVR of claim 40.w. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 205; x. The HVR of claim 40.x. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 207; y. The HVR of claim 40.y. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 209; z. The HVR of claim 40.z. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 234; aa. The HVR of claim 40.aa. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 235; bb. The HVR of claim 40.bb. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; cc. The HVR of claim 40.cc. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; dd. The HVR of claim 40.dd. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 238; ee. The HVR of claim 40.ee. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; ff. The HVR of claim 40.ff. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; gg. The HVR of claim 40.gg. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; hh. The HVR of claim 40.hh. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; ii. The HVR of claim 40.ii. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 238; jj. The HVR of claim 40.jj. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; kk. The HVR of claim 40.kk. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 239; 11. The HVR of claim 40.

11. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; mm. The HVR of claim 40. mm. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; nn. The HVR of claim 40.nn. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; oo. The HVR of claim 40.oo. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; pp. The HVR of claim 40.pp. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; or qq. The HVR of claim 40.qq. and further comprising a VH comprising the amino acid sequence of SEQ ID NO:

240.

44. The antibody of any one of claims 40 to 43, wherein the antibody comprises: a. The HVR of claim 40.a. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 162; b. The HVR of claim 40.b. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 164; c. The HVR of claim 40.c. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; d. The HVR of claim 40.d. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 168; e. The HVR of claim 40.e. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 170; f. The HVR of claim 40.f. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 172; g. The HVR of claim 40.g. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 174; h. The HVR of claim 40.h. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 176; i. The HVR of claim 40.i. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 178; j. The HVR of claim 40.j. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 180; k. The HVR of claim 40.k. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 182; 1. The HVR of claim 40.

1. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 184; m. The HVR of claim 40.m. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 186; n. The HVR of claim 40.n. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 188; o. The HVR of claim 40.o. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 190; p. The HVR of claim 40.p. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 192; q. The HVR of claim 40.q. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 194; r. The HVR of claim 40.r. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 196; s. The HVR of claim 40.s. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 198; t. The HVR of claim 40.t. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 200; u. The HVR of claim 40.u. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 202; v. The HVR of claim 40.v. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 204; w. The HVR of claim 40.w. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 206; x. The HVR of claim 40.x. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 208; y. The HVR of claim 40.y. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 210 z. The HVR of claim 40.z. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 241; aa. The HVR of claim 40.aa. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 242; bb. The HVR of claim 40.bb. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 243; cc. The HVR of claim 40.cc. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 243; dd. The HVR of claim 40.dd. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 244; ee. The HVR of claim 40.ee. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 245; ff. The HVR of claim 40.ff. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 245; gg. The HVR of claim 40.gg. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 246; hh. The HVR of claim 40.hh. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 247; ii. The HVR of claim 40.ii. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 247; jj. The HVR of claim 40.jj. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 248; kk. The HVR of claim 40.kk. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 249; 11. The HVR of claim 40.

11. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 250; mm. The HVR of claim 40. mm. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 251; nn. The HVR of claim 40.nn. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 252; oo. The HVR of claim 40.oo. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 253; pp. The HVR of claim 40.pp. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 254; or qq. The HVR of claim 40.qq. and further comprising a VL comprising the amino acid sequence of SEQ ID NO:

249.

45. The antibody of claim 40, wherein the antibody comprises a. a VH comprising the amino acid sequence of SEQ ID NO: 161 and a VL comprising the amino acid sequence of SEQ ID NO: 162 (as shown in Table 1); b. a VH comprising the amino acid sequence of SEQ ID NO: 163 and a VL comprising the amino acid sequence of SEQ ID NO: 164 (as shown in Table 1); c. a VH comprising the amino acid sequence of SEQ ID NO: 165 and a VL comprising the amino acid sequence of SEQ ID NO: 166 (as shown in Table 1); d. a VH comprising the amino acid sequence of SEQ ID NO: 167 and a VL comprising the amino acid sequence of SEQ ID NO: 168 (as shown in Table 1); e. a VH comprising the amino acid sequence of SEQ ID NO: 169 and a VL comprising the amino acid sequence of SEQ ID NO: 170 (as shown in Table 1); f. a VH comprising the amino acid sequence of SEQ ID NO: 171 and a VL comprising the amino acid sequence of SEQ ID NO: 172 (as shown in Table 1); g. a VH comprising the amino acid sequence of SEQ ID NO: 173 and a VL comprising the amino acid sequence of SEQ ID NO: 174 (as shown in Table 1); h. a VH comprising the amino acid sequence of SEQ ID NO: 175 and a VL comprising the amino acid sequence of SEQ ID NO: 176 (as shown in Table 1); i. a VH comprising the amino acid sequence of SEQ ID NO: 177 and a VL comprising the amino acid sequence of SEQ ID NO: 178 (as shown in Table 1); j. a VH comprising the amino acid sequence of SEQ ID NO: 179 and a VL comprising the amino acid sequence of SEQ ID NO: 180 (as shown in Table 1); k. a VH comprising the amino acid sequence of SEQ ID NO: 181 and a VL comprising the amino acid sequence of SEQ ID NO: 182 (as shown in Table 1); 1. A VH comprising the amino acid sequence of SEQ ID NO: 183 and a VL comprising the amino acid sequence of SEQ ID NO: 184 (as shown in Table 1); m. a VH comprising the amino acid sequence of SEQ ID NO: 185 and a VL comprising the amino acid sequence of SEQ ID NO: 186 (as shown in Table 1); n. a VH comprising the amino acid sequence of SEQ ID NO: 187 and a VL comprising the amino acid sequence of SEQ ID NO: 188 (as shown in Table 1); o. a VH comprising the amino acid sequence of SEQ ID NO: 189 and a VL comprising the amino acid sequence of SEQ ID NO: 190 (as shown in Table 1); p. VH comprising the amino acid sequence of SEQ ID NO: 191 and VL comprising the amino acid sequence of SEQ ID NO: 192 (as shown in Table 1); q. a VH comprising the amino acid sequence of SEQ ID NO: 193 and a VL comprising the amino acid sequence of SEQ ID NO: 194 (as shown in Table 1); r. VH comprising the amino acid sequence of SEQ ID NO: 195 and VL comprising the amino acid sequence of SEQ ID NO: 196 (as shown in Table 1); s. a VH comprising the amino acid sequence of SEQ ID NO: 197 and a VL comprising the amino acid sequence of SEQ ID NO: 198 (as shown in Table 1); t. a VH comprising the amino acid sequence of SEQ ID NO: 199 and a VL comprising the amino acid sequence of SEQ ID NO: 200 (as shown in Table 1); u. a VH comprising the amino acid sequence of SEQ ID NO: 201 and a VL comprising the amino acid sequence of SEQ ID NO: 202 (as shown in Table 1); v. a VH comprising the amino acid sequence of SEQ ID NO: 203 and a VL comprising the amino acid sequence of SEQ ID NO: 204 (as shown in Table 1); w. a VH comprising the amino acid sequence of SEQ ID NO: 205 and a VL comprising the amino acid sequence of SEQ ID NO: 206 (as shown in Table 1); x. a VH comprising the amino acid sequence of SEQ ID NO: 207 and a VL comprising the amino acid sequence of SEQ ID NO: 208 (as shown in Table 1); y. A VH comprising the amino acid sequence of SEQ ID NO: 209 and a VL comprising the amino acid sequence of SEQ ID NO: 210 (as shown in Table 1) z. a VH comprising the amino acid sequence of SEQ ID NO: 234 and a VL comprising the amino acid sequence of SEQ ID NO: 241 (as shown in Table 15); aa. VH comprising the amino acid sequence of SEQ ID NO: 235 and VL comprising the amino acid sequence of SEQ ID NO: 242 (as shown in Table 15); bb. a VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15); cc. VH comprising the amino acid sequence of SEQ ID NO: 237 and VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15); dd. a VH comprising the amino acid sequence of SEQ ID NO: 238 and a VL comprising the amino acid sequence of SEQ ID NO: 244 (as shown in Table 15); ee. VH comprising the amino acid sequence of SEQ ID NO: 236 and VL comprising the amino acid sequence of SEQ ID NO: 245 (as shown in Table 15); ff. a VH comprising the amino acid sequence of SEQ ID NO: 237 and a VL comprising the amino acid sequence of SEQ ID NO: 245 (as shown in Table 15); gg. VH comprising the amino acid sequence of SEQ ID NO: 236 and VL comprising the amino acid sequence of SEQ ID NO: 246 (as shown in Table 15); hh. VH comprising the amino acid sequence of SEQ ID NO: 237 and VL comprising the amino acid sequence of SEQ ID NO: 247 (as shown in Table 15); ii. a VH comprising the amino acid sequence of SEQ ID NO: 238 and a VL comprising the amino acid sequence of SEQ ID NO: 247 (as shown in Table 15); jj. A VH comprising the amino acid sequence of SEQ ID NO: 236 and a VL comprising the amino acid sequence of SEQ ID NO: 248 (as shown in Table 15); kk. VH comprising the amino acid sequence of SEQ ID NO: 239 and VL comprising the amino acid sequence of SEQ ID NO: 249 (as shown in Table 15); 11. VH comprising the amino acid sequence of SEQ ID NO: 240 and VL comprising the amino acid sequence of SEQ ID NO: 250 (as shown in Table 15); mm. VH comprising the amino acid sequence of SEQ ID NO: 240 and VL comprising the amino acid sequence of SEQ ID NO: 251 (as shown in Table 15); nn. VH comprising the amino acid sequence of SEQ ID NO: 240 and VL comprising the amino acid sequence of SEQ ID NO: 252 (as shown in Table 15); oo. VH comprising the amino acid sequence of SEQ ID NO: 240 and VL comprising the amino acid sequence of SEQ ID NO: 253 (as shown in Table 15); pp. a VH comprising the amino acid sequence of SEQ ID NO: 240 and a VL comprising the amino acid sequence of SEQ ID NO: 254 (as shown in Table 15); or qq. VH comprising the amino acid sequence of SEQ ID NO: 240 and VL comprising the amino acid sequence of SEQ ID NO: 249 (as shown in Table 15).

46. ​​The antibody of claim 40, wherein the antibody comprises: a. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 290; b. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 291; c. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 292; d. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 293; e. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 294; f. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 295; g. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 296; h. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 297; i. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 298; j. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 299; k. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 300; 1. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 301; m. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 302; n. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 303; o. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 304 p. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 305; q. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 306; r. The HVR of claim 40.z. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 307; s. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:308; t. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 309; u. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 310; v. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 311; w. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 312; x. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 313; y. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 314; z. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 315; aa. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:316; bb. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 317; cc. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 318; dd. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:319; ee. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 320; ff. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 321; gg. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 322; hh. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 323; ii. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 324; jj. The HVR of claim 40.aa. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 325; kk. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 326; 11. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327; mm. The HVR of claim 40.bb., claim 40.ee., claim 40.gg., or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 328; nn. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329; oo. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330; pp. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331; qq. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332; rr. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333; ss. The HVR of claim 40.bb., claim 40.ee., claim 40.gg., or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 334; tt. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:335; uu. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336; vv. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337; ww. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 338; xx. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:339; yy. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340; zz. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341; aaa. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342; bbb. The HVR of claim 40.bb., claim 40.ee., claim 40.gg. or claim 40.jj. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343; ccc. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 344; ddd. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 345; eee. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:346; fff. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 347; ggg. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 348; hhh. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349; iii. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350; jjj. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351; kkk. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 352; lll. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:353; mmm. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 354; nnn. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355; ooo. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 356; ppp. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:357; qqq. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:358; rrr. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:359; sss. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360; ttt. The HVR of claim 40.cc., ​​claim 40.ff. or claim 40.hh. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361; uuu. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 237; vvv. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 362; www. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 363; xxx. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 364; yyy. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 365; zzz. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 366; aaaa. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 367; bbbb. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:368; cccc. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 369; dddd. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 370; eeee. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 371; ffff. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 372; gggg. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 373; hhhh. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 374; iiii. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 375; jjjj. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 376; kkkk. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:377; llll. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 378; mmmm. The HVR of claim 40.dd. or claim 40.ii. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:379; nnnn. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 380; oooo. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 381; pppp. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 382; qqqq. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 383; rrrr. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 384; ssss. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:385; tttt. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 386; uuuu. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 387; vvvv. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 388; wwww. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 389; xxxx. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 390; yyyy. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 391; zzzz. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 392; aaaaa. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 393; bbbbb. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 394; ccccc. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 395; ddddd. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:396; eeeee. The HVR of claim 40.kk. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 397; fffff. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:398; ggggg. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:399; hhhhh. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:400; iiiii. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:401; jjjjj. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:402; kkkkk. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:403; lllll. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:404; mmmmm. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:405; nnnnn. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:406; ooooo. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:407; ppppp. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:408; qqqqq. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:409; rrrrr. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:410; sssss. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411; ttttt. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp., or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:412; uuuuu. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:413; vvvvv. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprising a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:414; or wwwww. The HVR of claim 40.ll., claim 40.mm., claim 40.nn., claim 40.oo., claim 40.pp. or claim 40.qq. and further comprises a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:

415.

47. The antibody of claim 40 or claim 46, wherein the antibody comprises: a. The HVR of claim 40.z. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; b. The HVR of claim 40.aa. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; c. The HVR of claim 40.bb. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; d. The HVR of claim 40.cc. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; e. The HVR of claim 40.dd. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:420; f. The HVR of claim 40.ee. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; g. The HVR of claim 40.ff. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; h. The HVR of claim 40.gg. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; i. The HVR of claim 40.hh. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; j. The HVR of claim 40.ii. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; k. The HVR of claim 40.jj. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:426; 1. The HVR of claim 40.kk. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; m. The HVR of claim 40.

11. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; n. The HVR of claim 40.mm. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:429; o. The HVR of claim 40.nn. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; p. The HVR of claim 40.oo. and further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:431; q. The HVR of claim 40.pp. and further comprising a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; or r. The HVR of claim 40.qq. and further comprising a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:

433.

48. The antibody of claim 40, wherein the antibody comprises: a. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 290 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; b. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 291 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; c. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 292 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; d. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 293 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; e. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 294 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; f. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 295 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; g. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 296 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; h. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 297 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; i. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 298 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; j. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 299 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; k. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 300 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; 1. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 301 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; m. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 302 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; n. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 303 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; o. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 304 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; p. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 305 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; q. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 306 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; r. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 307 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 416; s. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 308 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; t. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 309 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; u. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 310 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; v. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 311 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; w. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 312 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; x. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 313 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; y. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 314 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; z. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 315 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; aa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 316 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; bb. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 317 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; cc. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 318 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; dd. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 319 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; ee. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 320 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; ff. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 321 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; gg. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 322 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; hh. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 323 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; ii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 324 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; jj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 325 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 417; kk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; 11. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; mm. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; nn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; oo. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; pp. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; qq. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; rr. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; ss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; tt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; uu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; vv. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; ww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; xx. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; yy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; zz. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; aaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; bbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 418; ccc. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; ddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; eee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 346 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; fff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; ggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; hhh. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; iii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; jjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; kkk. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; lll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; mmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; nnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; ooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; ppp. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; qqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; rrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; sss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; ttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 419; uuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 362 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; vvv. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 363 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; www. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 364 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; xxx. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 365 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; yyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 366 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; zzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 367 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; aaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 368 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; bbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 369 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; cccc. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 370 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; dddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 371 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; eeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 372 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; ffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 373 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; gggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 374 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; hhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 375 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; iiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 376 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; jjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 377 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; kkkk. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 378 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; llll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 379 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 420; mmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; nnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; oooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; pppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; qqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; rrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; ssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; tttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; uuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; vvvv. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; wwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; xxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; yyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; zzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; aaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; bbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; ccccc. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; ddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 421; eeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; fffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; ggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 346 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; hhhhh. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; iiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; jjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; kkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; lllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; mmmmm. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; nnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; ooooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; ppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; qqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; rrrrr. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; sssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; ttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; uuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; vvvvv. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422; wwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; xxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; yyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; zzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; aaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; bbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; cccccc. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; dddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; eeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; ffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; gggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; hhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; iiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; jjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; kkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; llllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; mmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; nnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 423; oooooo. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 344 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; pppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 345 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; qqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 346 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; rrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 347 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; ssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 348 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; tttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 349 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; uuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 350 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; vvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 351 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; wwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 352 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; xxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 353 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; yyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 354 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; zzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 355 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; aaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 356 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; bbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 357 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; ccccccc. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 358 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; ddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 359 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; eeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 360 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; fffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 361 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 424; ggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 362 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; hhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 363 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; iiiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 364 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; jjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 365 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; kkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 366 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; lllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 367 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; mmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 368 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; nnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 369 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; ooooooo. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 370 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; ppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 371 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; qqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 372 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; rrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 373 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; sssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 374 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; ttttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 375 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; uuuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 376 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; vvvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 377 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; wwwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 378 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; xxxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 379 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 425; yyyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 326 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; zzzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 327 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; aaaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 328 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; bbbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 329 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; cccccccc. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 330 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; dddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 331 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; eeeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 332 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; ffffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 333 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; gggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 334 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; hhhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 335 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; iiiiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 336 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; jjjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 337 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; kkkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 338 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; llllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 339 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; mmmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 340 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; nnnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 341 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; oooooooo. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 342 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; pppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 343 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 426; qqqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 380 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; rrrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 381 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; ssssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 382 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; tttttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 383 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; uuuuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 384 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; vvvvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 385 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; wwwwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 386 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; xxxxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 387 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; yyyyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 388 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; zzzzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 389 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; aaaaaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 390 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; bbbbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 391 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; ccccccccc. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 392 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; ddddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 393 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; eeeeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 394 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; fffffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 395 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; ggggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 396 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; hhhhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 397 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 427; iiiiiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; jjjjjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; kkkkkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; lllllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; mmmmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; nnnnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; ooooooooo. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; ppppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; qqqqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; rrrrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; sssssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; ttttttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; uuuuuuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; vvvvvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; wwwwwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 412 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; xxxxxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 413 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; yyyyyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 414 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 428; zzzzzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:415 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:428; aaaaaaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; bbbbbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; cccccccccc. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; dddddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; eeeeeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; ffffffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; gggggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; hhhhhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; iiiiiiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; jjjjjjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; kkkkkkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; llllllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 429; mmmmmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; nnnnnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:429; oooooooooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; pppppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; qqqqqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; rrrrrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; ssssssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; tttttttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; uuuuuuuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; vvvvvvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; wwwwwwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; xxxxxxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; yyyyyyyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; zzzzzzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 430; aaaaaaaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; bbbbbbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:430; ccccccccccc. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; ddddddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; eeeeeeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; fffffffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; ggggggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; hhhhhhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; iiiiiiiiiii. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; jjjjjjjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; kkkkkkkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; lllllllllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; mmmmmmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; nnnnnnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; ooooooooooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 431; ppppppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:431; qqqqqqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; rrrrrrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; sssssssssss. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; ttttttttttt. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; uuuuuuuuuuuu. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; vvvvvvvvvvvv. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; wwwwwwwwwwwww. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; xxxxxxxxxxx. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; yyyyyyyyyyyy. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; zzzzzzzzzzz. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; aaaaaaaaaaaaa. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:432; bbbbbbbbbbbb. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; cccccccccccc. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; dddddddddddd. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 432; eeeeeeeeeeee. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 398 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; ffffffffffff. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 399 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; gggggggggggg. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 400 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; hhhhhhhhhhhh. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:401 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; iiiiiiiiiiii. a heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 402 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; jjjjjjjjjjjjj. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 403 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; kkkkkkkkkkkkk. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:404 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; llllllllllll. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 405 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; mmmmmmmmmmmm. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 406 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; nnnnnnnnnnnn. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 407 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; oooooooooooo. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 408 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; pppppppppppp. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 409 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 433; qqqqqqqqqqqq. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:410 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:433; or rrrrrrrrrrrr. A heavy chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:411 and a light chain that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO:

433.

49. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises: a. a heavy chain comprising the amino acid sequence of SEQ ID NO: 290 or SEQ ID NO: 291 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; b. a heavy chain comprising the amino acid sequence of SEQ ID NO: 292 or SEQ ID NO: 293 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; c. a heavy chain comprising the amino acid sequence of SEQ ID NO: 294 or SEQ ID NO: 295 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; d. a heavy chain comprising the amino acid sequence of SEQ ID NO: 296 or SEQ ID NO: 297 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; e. a heavy chain comprising the amino acid sequence of SEQ ID NO: 298 or SEQ ID NO: 299 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; f. A heavy chain comprising the amino acid sequence of SEQ ID NO: 300, SEQ ID NO: 301 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; g. a heavy chain comprising the amino acid sequence of SEQ ID NO: 302 or SEQ ID NO: 303 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; h. a heavy chain comprising the amino acid sequence of SEQ ID NO: 304, SEQ ID NO: 305 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; i. a heavy chain comprising the amino acid sequence of SEQ ID NO: 306 or SEQ ID NO: 307 and a light chain comprising the amino acid sequence of SEQ ID NO: 416; j. a heavy chain comprising the amino acid sequence of SEQ ID NO: 308 or SEQ ID NO: 309 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; k. a heavy chain comprising the amino acid sequence of SEQ ID NO: 310 or SEQ ID NO: 311 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; 1. A heavy chain comprising the amino acid sequence of SEQ ID NO: 312 or SEQ ID NO: 313 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; m. a heavy chain comprising the amino acid sequence of SEQ ID NO: 314 or SEQ ID NO: 315 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; n. A heavy chain comprising the amino acid sequence of SEQ ID NO: 316 or SEQ ID NO: 317 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; o. a heavy chain comprising the amino acid sequence of SEQ ID NO: 318 or SEQ ID NO: 319 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; p. a heavy chain comprising the amino acid sequence of SEQ ID NO: 320 or SEQ ID NO: 321 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; q. a heavy chain comprising the amino acid sequence of SEQ ID NO: 322 or SEQ ID NO: 323 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; r. a heavy chain comprising the amino acid sequence of SEQ ID NO: 324 or SEQ ID NO: 325 and a light chain comprising the amino acid sequence of SEQ ID NO: 417; s. a heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; t. a heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; u. a heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; v. a heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; w. a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; x. a heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; y. a heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; z. a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; aa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: 418; bb. a heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; cc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; dd. a heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; ee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; ff. a heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; gg. A heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; hh. A heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; ii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; jj. A heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: 361 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; kk. A heavy chain comprising the amino acid sequence of SEQ ID NO: 362 or SEQ ID NO: 363 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; 11. A heavy chain comprising the amino acid sequence of SEQ ID NO: 364 or SEQ ID NO: 365 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; mm. A heavy chain comprising the amino acid sequence of SEQ ID NO: 366 or SEQ ID NO: 367 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; nn. A heavy chain comprising the amino acid sequence of SEQ ID NO: 368 or SEQ ID NO: 369 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; oo. A heavy chain comprising the amino acid sequence of SEQ ID NO: 370 or SEQ ID NO: 371 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; pp. a heavy chain comprising the amino acid sequence of SEQ ID NO: 372 or SEQ ID NO: 373 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; qq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 374 or SEQ ID NO: 375 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; rr. A heavy chain comprising the amino acid sequence of SEQ ID NO: 376 or SEQ ID NO: 377 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; ss. A heavy chain comprising the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 379 and a light chain comprising the amino acid sequence of SEQ ID NO: 420; tt. A heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; uu. A heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; vv. A heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; ww. A heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; xx. a heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; yy. A heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; zz. A heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; aaa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; bbb. A heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: 421; ccc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; ddd. A heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; eee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; fff. A heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; ggg. A heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; hhh. A heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; iii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; jjj. A heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; kkk. A heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: 361 and a light chain comprising the amino acid sequence of SEQ ID NO: 422; lll. A heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; mmm. A heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; nnn. A heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; ooo. A heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; ppp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; qqq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; rrr. A heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; sss. A heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; ttt. A heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: 423; uuu. A heavy chain comprising the amino acid sequence of SEQ ID NO: 344 or SEQ ID NO: 345 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; vvv. A heavy chain comprising the amino acid sequence of SEQ ID NO: 346 or SEQ ID NO: 347 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; www. A heavy chain comprising the amino acid sequence of SEQ ID NO: 348 or SEQ ID NO: 349 and a light chain comprising the amino acid sequence of SEQ ID NO: 419; xxx. A heavy chain comprising the amino acid sequence of SEQ ID NO: 350 or SEQ ID NO: 351 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; yyy. A heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or SEQ ID NO: 353 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; zzz. A heavy chain comprising the amino acid sequence of SEQ ID NO: 354 or SEQ ID NO: 355 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; aaaa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 356 or SEQ ID NO: 357 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; bbbb. A heavy chain comprising the amino acid sequence of SEQ ID NO: 358 or SEQ ID NO: 359 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; cccc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 360 or SEQ ID NO: 361 and a light chain comprising the amino acid sequence of SEQ ID NO: 424; dddd. A heavy chain comprising the amino acid sequence of SEQ ID NO: 362 or SEQ ID NO: 363 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; eeee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 364 or SEQ ID NO: 365 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; ffff. A heavy chain comprising the amino acid sequence of SEQ ID NO: 366 or SEQ ID NO: 367 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; gggg. A heavy chain comprising the amino acid sequence of SEQ ID NO: 368 or SEQ ID NO: 369 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; hhhh. A heavy chain comprising the amino acid sequence of SEQ ID NO: 370 or SEQ ID NO: 371 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; iiii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 372 or SEQ ID NO: 373 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; jjjj. A heavy chain comprising the amino acid sequence of SEQ ID NO: 374 or SEQ ID NO: 375 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; kkkk. A heavy chain comprising the amino acid sequence of SEQ ID NO: 376 or SEQ ID NO: 377 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; llll. A heavy chain comprising the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 379 and a light chain comprising the amino acid sequence of SEQ ID NO: 425; mmmm. A heavy chain comprising the amino acid sequence of SEQ ID NO: 326 or SEQ ID NO: 327 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; nnnn. A heavy chain comprising the amino acid sequence of SEQ ID NO: 328 or SEQ ID NO: 329 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; oooo. A heavy chain comprising the amino acid sequence of SEQ ID NO: 330 or SEQ ID NO: 331 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; pppp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 332 or SEQ ID NO: 333 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; qqqq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 334 or SEQ ID NO: 335 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; rrrr. A heavy chain comprising the amino acid sequence of SEQ ID NO: 336 or SEQ ID NO: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; ssss. A heavy chain comprising the amino acid sequence of SEQ ID NO: 338 or SEQ ID NO: 339 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; tttt. A heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or SEQ ID NO: 341 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; uuuu. A heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or SEQ ID NO: 343 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; vvvv. A heavy chain comprising the amino acid sequence of SEQ ID NO: 380 or SEQ ID NO: 381 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; wwww. A heavy chain comprising the amino acid sequence of SEQ ID NO: 382 or SEQ ID NO: 383 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; xxxx. A heavy chain comprising the amino acid sequence of SEQ ID NO: 384 or SEQ ID NO: 385 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; yyyy. A heavy chain comprising the amino acid sequence of SEQ ID NO: 386 or SEQ ID NO: 387 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; zzzz. A heavy chain comprising the amino acid sequence of SEQ ID NO: 388 or SEQ ID NO: 389 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; aaaaa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 390 or SEQ ID NO: 391 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; bbbbb. A heavy chain comprising the amino acid sequence of SEQ ID NO: 392 or SEQ ID NO: 393 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; ccccc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 394 or SEQ ID NO: 395 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; ddddd. A heavy chain comprising the amino acid sequence of SEQ ID NO: 396 or SEQ ID NO: 397 and a light chain comprising the amino acid sequence of SEQ ID NO: 427; eeeee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; fffff. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; ggggg. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; hhhhh. A heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; iiiii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; jjjjj. A heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; kkkkk. A heavy chain comprising the amino acid sequence of SEQ ID NO:410 or SEQ ID NO:411 and a light chain comprising the amino acid sequence of SEQ ID NO:428; lllll. A heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; mmmmm. A heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 428; nnnnn. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; ooooo. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; ppppp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; qqqqq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; rrrrr. A heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; sssss. A heavy chain comprising the amino acid sequence of SEQ ID NO:408 or SEQ ID NO:409 and a light chain comprising the amino acid sequence of SEQ ID NO:429; ttttt. A heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; uuuuu. A heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; vvvvv. A heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 429; wwwww. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; xxxxx. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; yyyyy. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; zzzzz. A heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; aaaaaa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; bbbbbb. A heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; cccccc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; dddddd. A heavy chain comprising the amino acid sequence of SEQ ID NO:412 or SEQ ID NO:413 and a light chain comprising the amino acid sequence of SEQ ID NO:430; eeeeee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 430; ffffff. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; gggggg. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; hhhhhh. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; iiiiii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; jjjjjj. A heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; kkkkkk. A heavy chain comprising the amino acid sequence of SEQ ID NO:408 or SEQ ID NO:409 and a light chain comprising the amino acid sequence of SEQ ID NO:431; llllll. A heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; mmmmmm. A heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 431; nnnnnn. A heavy chain comprising the amino acid sequence of SEQ ID NO:414 or SEQ ID NO:415 and a light chain comprising the amino acid sequence of SEQ ID NO:431; oooooo. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; pppppp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; qqqqqq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; rrrrrr. A heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; ssssss. A heavy chain comprising the amino acid sequence of SEQ ID NO:406 or SEQ ID NO:407 and a light chain comprising the amino acid sequence of SEQ ID NO:432; tttttt. A heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; uuuuuu. A heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; vvvvvv. A heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; wwwwww. A heavy chain comprising the amino acid sequence of SEQ ID NO: 414 or SEQ ID NO: 415 and a light chain comprising the amino acid sequence of SEQ ID NO: 432; xxxxxx. A heavy chain comprising the amino acid sequence of SEQ ID NO: 398 or SEQ ID NO: 399 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; yyyyyy. A heavy chain comprising the amino acid sequence of SEQ ID NO: 400 or SEQ ID NO: 401 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; zzzzzz. A heavy chain comprising the amino acid sequence of SEQ ID NO: 402 or SEQ ID NO: 403 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; aaaaaaa. A heavy chain comprising the amino acid sequence of SEQ ID NO: 404 or SEQ ID NO: 405 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; bbbbbbb. A heavy chain comprising the amino acid sequence of SEQ ID NO: 406 or SEQ ID NO: 407 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; ccccccc. A heavy chain comprising the amino acid sequence of SEQ ID NO: 408 or SEQ ID NO: 409 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; ddddddd. A heavy chain comprising the amino acid sequence of SEQ ID NO: 410 or SEQ ID NO: 411 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; eeeeeee. A heavy chain comprising the amino acid sequence of SEQ ID NO: 412 or SEQ ID NO: 413 and a light chain comprising the amino acid sequence of SEQ ID NO: 433; or fffffff. A heavy chain comprising the amino acid sequence of SEQ ID NO:414 or SEQ ID NO:415 and a light chain comprising the amino acid sequence of SEQ ID NO:

433.

50. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises: a VH comprising HVR-H1, HVR-H2 and HVR-H3 of any one of the following antibodies and a VL comprising HVR-L1, HVR-L2 and HVR-L3 of any one of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31 , GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83 , GPN-84, GPN-85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98.

51. The isolated antibody of claim 50, wherein the antibody comprises a VH and / or VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH and / or VL of any of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35 , GPN-37, GPN-38, GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84, GPN -85, GPN-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98.

52. The isolated antibody of claim 50 or claim 51, wherein the antibody comprises the VH and / or VL of any of the following antibodies: GPN-01, GPN-03, GPN-06, GPN-07, GPN-08, GPN-09, GPN-11, GPN-22, GPN-24, GPN-25, GPN-26, GPN-30, GPN-31, GPN-33, GPN-34, GPN-35, GPN-37, GPN-38, GPN-39, GPN-40, GPN-41, GPN-42, GPN-43, GPN-44, GPN-45, GPN-46, GPN-47, GPN-48, GPN-49, GPN-50, GPN-51, GPN-52, GPN-53, GPN-54, GPN-55, GPN-56, GPN-57, GPN-58, GPN-59, GPN-60, GPN-61, GPN-62, GPN-63, GPN-64, GPN-65 8. GPN-41, GPN-42, GPN-43, GPN-48, GPN-52, GPN-61, GPN-65, GPN-81, GPN-82, GPN-83, ​​GPN-84, GPN-85, GP N-86, GPN-87, GPN-88, GPN-89, GPN-90, GPN-91, GPN-92, GPN-93, GPN-94, GPN-95, GPN-96, GPN-97 and GPN-98.

53. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody comprises: a. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-01 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-01 (as shown in Table 3); b. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-03 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-03 (as shown in Table 3); c. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-06 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-06 (as shown in Table 3); d. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-07 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-07 (as shown in Table 3); e. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-08 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-08 (as shown in Table 3); f. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-09 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-09 (as shown in Table 3); g. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-11 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-11 (as shown in Table 3); h. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-22 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-22 (as shown in Table 3); i. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-24 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-24 (as shown in Table 3); j. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-25 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-25 (as shown in Table 3); k. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-26 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-26 (as shown in Table 3); 1. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-30 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-30 (as shown in Table 3); m. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-31 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-31 (as shown in Table 3); n. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-33 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-33 (as shown in Table 3); o. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-34 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-34 (as shown in Table 3); p. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-35 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-35 (as shown in Table 3); q. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-37 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-37 (as shown in Table 3); r. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-38 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-38 (as shown in Table 3); s. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-41 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-41 (as shown in Table 3); t. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-42 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-42 (as shown in Table 3); u. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-43 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-43 (as shown in Table 3); v. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-48 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-48 (as shown in Table 3); w. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-52 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-52 (as shown in Table 3); x. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-61 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-61 (as shown in Table 3); or y. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-65 (as shown in Table 2) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-65 (as shown in Table 3) z. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-81 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-81 (as shown in Table 17); aa. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-82 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-82 (as shown in Table 17); bb. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-83 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-83 (as shown in Table 17); cc. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-84 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-84 (as shown in Table 17); dd. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-85 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-85 (as shown in Table 17); ee. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-86 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-86 (as shown in Table 17); ff. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-87 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-87 (as shown in Table 17); gg. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-88 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-88 (as shown in Table 17); hh. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-89 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-89 (as shown in Table 17); ii. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-90 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-90 (as shown in Table 17); jj. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-91 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-91 (as shown in Table 17); kk. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-92 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-92 (as shown in Table 17); 11. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-93 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-93 (as shown in Table 17); mm. VH and VL, wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-94 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-94 (as shown in Table 17); nn. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-95 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-95 (as shown in Table 17); oo. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-96 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-96 (as shown in Table 17); pp. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-97 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-97 (as shown in Table 17); or qq. VH and VL, wherein the VH comprises HVR-H1, HVR-H2 and HVR-H3 of antibody GPN-98 (as shown in Table 16) and the VL comprises HVR-L1, HVR-L2 and HVR-L3 of antibody GPN-98 (as shown in Table 17).

54. The antibody of any one of claims 32 to 53, wherein the antibody antagonizes GPNMB activity.

55. The antibody of any one of claims 32 to 54, wherein the antibody has one or more of the following properties: a. The antibody regulates the expression of activation surface markers on myeloid cells; b. the antibody increases the cell surface expression of PD-L1 in human macrophages; c. the antibody increases the cell surface expression of CD40 in human macrophages; d. the antibody increases the cell surface expression of CD80 in human macrophages; e. the antibody modulates lysosomal function in myeloid cells; f. The antibody increases glucocerebrosidase activity in human macrophages; g. The antibody reduces cell surface expression of GPNMB on human macrophages; h. The antibody changes the interferon pathway gene expression pattern in human macrophages; i. The antibody reduces tumor volume in a mouse tumor model, such as the MC38 tumor model; j. The antibody reduces the tumor growth rate in a mouse model, such as the MC38 tumor model; k. The antibody increases the level of IL-12p40 in serum; 1. The antibody increases the level of CCL5 in serum; m. The antibody is a GPNMB ligand blocking antibody; n. The antibody is a non-blocking antibody; o. The antibody antagonizes GPNMB activity, regardless of ligand blocking activity; p. The antibody antagonizes GPNMB activity in vivo; q. the antibody binds to GPNMB expressed on the cell surface; r. the antibody promotes macrophage activation; s. The antibody overcomes the reduction in glucocerebrosidase activity associated with reduced levels of progranulin; t. The antibody reduces the expression level of GPNMB in cells, optionally macrophages; u. The antibody reduces the expression level of LAMP2 in cells, optionally macrophages, monocytes or neutrophils; v. the antibody inhibits or reduces inflammasome activation; w. The antibody inhibits IL-1β expression or release; x. The antibody reduces neuroinflammation; y. The antibody reduces the expression of C1q, GFAP, IBA1 and CTSD associated with neuroinflammation; and z. The antibody reduces lysosomal stress.

56. The antibody of any one of claims 1 to 55, wherein the antibody binds to human GPNMB, binds to mouse GPNMB, binds to cynomolgus monkey GMNMB, binds to both human and mouse GPNMB, or binds to human, mouse and cynomolgus monkey GPNMB.

57. An antibody as described in any one of claims 1 to 56, wherein the antibody binds to human GPNMB with an affinity of about 0.4nM to about 120nM, about 0.3nM to about 5nM, about 0.4nM to about 1.04nM, about 0.14 to about 0.65nM and binds to mouse GPNMB with an affinity of about 0.18nM to about 0.44nM.

58. The antibody of any one of claims 1 to 57, wherein the antibody is a monoclonal antibody.

59. The antibody of any one of claims 1 to 58, wherein the antibody is a humanized antibody.

60. The antibody of any one of claims 1 to 59, wherein the antibody is an antigen binding fragment, such as a Fab, Fab', Fab'-SH, F(ab')2, Fv or scFv fragment.

61. The antibody of any one of claims 1 to 60, wherein the antibody is a bispecific or multispecific antibody.

62. The antibody of any one of claims 1 to 61, wherein the antibody is of the IgG class, the IgM class or the IgA class.

63. The antibody of claim 62, wherein the antibody is of the IgG class and is of the human IgGl, IgG2, IgG3 or IgG4 isotype or the mouse IgGl or IgG2 isotype.

64. The antibody of any one of claims 1 to 63, wherein the antibody binds to an inhibitory Fc receptor.

65. The antibody of claim 64, wherein the inhibitory Fc receptor is inhibitory Fc-gamma receptor IIB (FcgRIIB).

66. The antibody of claim 65, wherein the antibody reduces cellular levels of FcgRIIB.

67. The antibody of any one of claims 1 to 45 or 50 to 66, wherein the antibody has a human or mouse IgG1 isotype and comprises one or more amino acid substitutions at amino acid residues in the Fc region selected from the group consisting of: N297A, D265A, D270A, L234A, L235A, G237A, P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E233P, L234V, L234F, L235E, P336A, 31S, P331G, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q, A327G, P329A, P329S, P329G, K322A, N325S, T394D, A330S, E430G, E430S, E430F, E430T, E345K, E345Q, E345R, E345Y, S440Y, S440W, and any combination thereof, wherein the numbering of the residues is according to the EU numbering.

68. The antibody of any one of claims 1 to 45 or 50 to 67, wherein the antibody has a human or mouse IgG2 isotype and comprises one or more amino acid substitutions at amino acid residues in the Fc region selected from the group consisting of A330S, C127S, C214S, C219S, C220S, E345K, E345Q, E345R, E345Y, E430F, E430G, E430S, E430T, G237A, H268Q, L328F, M252Y, P331S, S254T, S267E, S440W, S440Y, T256E, V234A, V309L, and any combination thereof, wherein the numbering of the residues is according to EU numbering.

69. The antibody of any one of claims 1 to 45 or 50 to 68, wherein the antibody has a human or mouse IgG4 isotype and comprises one or more amino acid substitutions at amino acid residues in the Fc region selected from the group consisting of: C127S, E318A, E345R, E430G, F234A, G237A, K322A, L235A, L235E, L236E, L243A, L328F, M252Y, P331S, S228P, S229P, S254T, S267E, S440Y, T256E, and any combination thereof, wherein the numbering of the residues is according to EU numbering.

70. The antibody of any one of claims 1 to 45 or 50 to 69, wherein the antibody comprises one or more amino acid substitutions at a residue position in the Fc region selected from the group consisting of: A330L, A330S, C127S, E345R, E430G, K322A, L234A, L234F, L235A, L235E, L243A, L328F, P331S, S267E, S440Y, and any combination thereof, wherein the numbering of the amino acid residues is according to EU or Kabat numbering.

71. The antibody of any one of claims 1 to 45 or 50 to 70, wherein the IgG Fc amino acid sequence is selected from the group consisting of SEQ ID NOs: 213-233.

72. A pharmaceutical composition comprising the anti-GPNMB antibody of any one of claims 1 to 71 and a pharmaceutically acceptable carrier.

73. An isolated nucleic acid comprising a nucleic acid sequence encoding the anti-GPNMB antibody of any one of claims 1 to 71.

74. An isolated vector comprising the nucleic acid of claim 73.

75. An isolated host cell comprising the nucleic acid of claim 73 or the vector of claim 74.

76. A method of producing an anti-GPNMB antibody, comprising culturing the cell of claim 75 so that the antibody is produced.

77. The method of claim 76, further comprising recovering antibodies produced by the cells.

78. A method of treating cancer in a subject in need thereof, the method comprising administering to an individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody of any one of claims 1 to 71, thereby treating the cancer.

79. The method of claim 78, further comprising administering one or more therapeutic agents.

80. The method of claim 79, wherein at least one therapeutic agent is a checkpoint inhibitor.

81. The method of claim 80, wherein the checkpoint inhibitor is selected from PD1, PD-L1, and PD-L2 inhibitors.

82. The method of claim 80 or 81, wherein the checkpoint inhibitor is selected from an anti-PD-L1 antibody, an anti-PD-L2 antibody, and an anti-PD-1 antibody.

83. The method of any one of claims 78 to 82, wherein the cancer is a sarcoma, bladder cancer, breast cancer, colon cancer, endometrial cancer, kidney cancer (renal cancer), leukemia, lung cancer, non-small cell lung cancer, melanoma, lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, gastric cancer, thyroid cancer, uterine cancer, liver cancer, cervical cancer, testicular cancer, squamous cell carcinoma, glioma, glioblastoma, adenoma or neuroblastoma.

84. The method of any one of claims 78 to 83, wherein the cancer is glioblastoma multiforme, bladder cancer, esophageal cancer, or triple-negative breast cancer.

85. A method of treating a neurodegenerative disease or disorder in a subject in need thereof, the method comprising administering to an individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody as described in any one of claims 1 to 71, thereby treating the disease or disorder.

86. The method of claim 85, wherein the disease or disorder is selected from Parkinson's disease, Alzheimer's disease, and ALS.

87. A method of treating a lysosomal storage disease or disorder in a subject in need thereof, the method comprising administering to an individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody of any one of claims 1 to 71, thereby treating the disease or disorder.

88. The method of claim 87, wherein the lysosomal storage disease is Gaucher disease.

89. A method for detecting the presence of GPNMB in an in vitro sample or an individual, the method comprising the anti-GPNMB antibody of any one of claims 1 to 71.

90. The method of claim 89, further comprising quantifying antigen-bound anti-GPNMB antibodies.

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