Anti-GPNMB antibodies and methods of use thereof

Abstract

The present disclosure is generally directed to compositions comprising monovalent antibodies, e.g., monoclonal monovalent antibodies that specifically bind to a GPNMB polypeptide, e.g., a mammalian GPNMB polypeptide or a human GPNMB polypeptide, and to the use of such compositions in treating individuals in need of treatment.

Description

[Technical Field]

[0001] Sequence Listing This application has been submitted electronically in XML format along with a Sequence Listing, which is incorporated herein 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.

[0002] Field of the Disclosure The present disclosure relates to anti-GPNMB antibodies and uses (eg, therapeutic uses) of such antibodies. [Background technology]

[0003] Background of the Disclosure The glycoprotein nonmetastatic melanoma protein B (GPNMB), also known as osteoactivin (rat orthologue), dendritic cell-heparin integrin ligand (DC-HIL, mouse orthologue), or hematopoietic growth factor-inducible neurokinin-type 1 (HGFIN), is a type 1 transmembrane protein.

[0004] Increased expression of GPNMB is associated with a genome-wide significant risk of 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, as well as certain lysosomal storage disorders, including Gaucher disease and Niemann-Pick type C disease (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).

[0005] Furthermore, 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).

[0006] Anti-GPNMB antibodies have been previously described, see, e.g., WO2006 / 071441, WO2007 / 053718, US2007 / 0190575, US2013 / 0156784, USPN7,115,265, WO2008 / 133641, WO2010 / 135547, WO2016 / 145022, WO2017 / 046061, WO2018 / 217945, and WO2019 / 137138.

[0007] For example, there is a need for novel therapeutic anti-GPNMB antibodies with antagonistic activity that are effective in treating a variety of diseases, disorders, and conditions associated with GPNMB, including cancer, neurodegenerative diseases including Parkinson's disease, and lysosomal storage disorders.

[0008] All references cited herein, including patent applications and publications, are hereby incorporated by reference in their entirety. Summary of the Invention

[0009] Summary of the Disclosure The present disclosure is generally directed to anti-GPNMB antibodies and methods of using such antibodies.

[0010] The present disclosure fills 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 nonmetastatic melanoma protein B (GPNMB) antibodies, which antagonize GPNMB activity. In some embodiments, the anti-GPNMB antibody modulates the expression of activation surface markers in myeloid cells, increases the cell surface expression of PD-L1 in human macrophages, increases the cell surface expression of CD40 in human macrophages, increases the cell surface expression of CD80 in human macrophages, modulates lysosomal function in myeloid cells, increases glucocerebrosidase activity in human macrophages, decreases the cell surface expression of GPNMB in human macrophages, alters interferon pathway gene expression patterns in human macrophages, reduces tumor volume in mouse tumor models such as the MC38 model, reduces tumor growth rates in mouse tumor models such as the MC38 model, increases the level of IL-12p40 in serum, and increases the level of CCL in serum. 5, is a GPNMB ligand blocking antibody, is a non-blocking antibody, antagonizes GPNMB activity independent of ligand blocking activity, antagonizes GPNMB activity in vivo, the antibody binds to GPNMB expressed on the cell surface that promotes macrophage activation, overcomes decreased glucocerebrosidase activity associated with decreased progranulin levels, reduces GPNMB expression levels in cells, optionally macrophages, reduces LAMP2 expression levels in cells, optionally macrophages, monocytes, or neutrophils, inhibits or reduces inflammasome activation, inhibits IL-1β expression or release, reduces neuroinflammation, reduces expression of C1q, GFAP, IBA1, and CTSD associated with neuroinflammation, and / or reduces lysosomal stress.

[0011] In some cases, the anti-GPNMB antibody is 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, GPN-66, GPN-67, GPN-68, GPN-69, GPN-70, GPN-71, GPN-72, GPN-73, GPN-74, GPN-75, GPN-76, GPN-77, GPN-78, GPN-79, GPN-80, 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, GPN-99, GPN-100, GPN-101, GPN-102, GPN-103, GPN- The antibody competes with one or more antibodies selected from 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. In some cases, 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 are 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-48, GPN-52, GPN-61, GPN-62, GPN-63, GPN-64, GPN-65, GPN-66, GPN-67, GPN-68, GPN-69, GPN-70, GPN-71, GPN-72, GPN-73, GPN-74, GPN-75, GPN-76, GPN-77, GPN-78, GPN-79, GPN-80, 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, GPN-99, GPN-100, GPN-101, GPN-102, GPN-103, GPN-104, GPN-105, GPN-106, GPN-107, GPN-108, GPN-109, GPN-110, GPN-111, GPN-112, GPN 5, 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, and comprising 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-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, (a) HVR-H1 comprises an amino acid sequence selected from the group consisting 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 (b) HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 9, 12, 15, 18,(c) HVR-H3 comprises an amino acid sequence selected from the group consisting 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; and (d) HVR-L1 is selected from the group consisting 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, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 33 7, and 268; and (e) HVR-L2 comprises an amino acid sequence selected from the group consisting 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 / or (f) HVR-L3 comprises an amino acid sequence selected from the group consisting 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. 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, and 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 comprisesor 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: 16. wherein 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 wherein HVR-H1 comprises the amino acid sequence of SEQ ID NO: 17, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 18, and 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 wherein HVR-H1 comprises the amino acid sequence of SEQ ID NO: 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: 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, and 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, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: 28, or 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, and HVR-H2HVR-H1 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, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 34, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 110, and 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, and HVR-H3 HVR-H1 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: 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 wherein 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 wherein 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, and HVR-L1 comprisesHVR-H1 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, HVR-H3 comprises the amino acid sequence of SEQ ID 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, and HVR-L2 comprises HVR-H1 comprises the amino acid sequence of SEQ ID 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, and 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 comprisesor HVR-H1 comprises the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 69, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 70, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 146, and HVR, HVR-H1 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 and 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 and HVR-H2 comprises the amino acid sequence of SEQ ID NO: 7 HVR-H1 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: 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 -HVR-L3 comprises the amino acid sequence of SEQ ID NO: 157, or 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, and HVR-H3 comprises the amino acid sequence of SEQ ID NO: 7 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, and HVR-H3 comprises the amino acid sequence of SEQ 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, orAlternatively, 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, and HVR-L1 HVR-H1 comprises the amino acid sequence of SEQ ID NO: 266, 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, and 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: 73, and 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 and HVR-H2 comprises the amino acid sequence of SEQ ID NO: 257 and HVR-H3 comprises the amino acid sequence of SEQ ID NO: 261 and HVR-L1 comprises the amino acid sequence of SEQ ID NO: 264 and 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 and HVR-H2HVR-H1 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: 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, and HVR-L2 comprises the amino acid sequence of SEQ ID NO: 272. and HVR-H1 comprises the amino acid sequence of SEQ ID NO: 23, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 259, and 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: 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: 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, and 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: 262, 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.

[0012] 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; HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 255, 256, 257, 258, 259, and 260, and 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. In some cases, 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; , 141, 144, 147, 150, 153, 156, 269, 270, 271, 272, 273, 274, 275, 276, and 277, and 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.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: 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 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 sequence numbers 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 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 VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, insertions, and / or deletions compared 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. The amino acid sequence of any one of the sequences selected from the group consisting of: 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, contains 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions, insertions, and / or deletions.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 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.

[0013] The present disclosure further relates to 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 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 VL comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:8, HVR-L2 comprising the amino acid sequence of SEQ ID NO:9, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:10. a VH comprising an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; and a VL comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 86, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 87, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 88; or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 12, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 13, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 89 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 90. and HVR-L2 comprising the amino acid sequence of SEQ ID NO: 91, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 15, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 16, and a VL comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 92, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 93, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 94, or an HV comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 17 and an amino acid sequence of SEQ ID NO: 18. a VH comprising R-H2 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 HVR-L1 comprising the amino acid sequence of SEQ ID NO: 98 and HVR-L2 comprising the amino acid sequence of SEQ ID NO: 99;and 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: 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 an 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 a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 105, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 29, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 31, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 107 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 108; and a VL 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 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 an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 35 and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36, and a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 113, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 115, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 38, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 116 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117;and a VL 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 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 an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 44 and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 45, and a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 123, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 47, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 125 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 126; and a VL 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 an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 53 and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 131, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 132, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 56, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 57, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 58, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 134 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 135;and a VL 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 an 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 a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 141, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 142, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 67, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 143 and an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 144; and a VL comprising 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 an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71 and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72, and a VH comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 149, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 150, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 151, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 74, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 75, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 76, and an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 152 and an 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 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 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 HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 255, a VH comprising HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 263, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 269, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 151, or a VL comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 256, an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 270, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278; a VL comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, a VH comprising an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 265, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 271, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278, or an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, or an HVR comprising the amino acid sequence of SEQ ID NO: 261 a VH comprising HVR-H3, 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 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: 258, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, 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 VL comprising HVR-H1 having the amino acid sequence of SEQ ID NO: 71, HVR-H2 having the amino acid sequence of SEQ ID NO: 257, HVR-H3 having the amino acid sequence of SEQ ID NO: 73, HVR-L1 having the amino acid sequence of SEQ ID NO: 264, HVR-L2 having the amino acid sequence of SEQ ID NO: 273, and HVR-L3 having the amino acid sequence of SEQ ID NO: 278; or a VH comprising HVR-H1 having the amino acid sequence of SEQ ID NO: 71, HVR-H2 having the amino acid sequence of SEQ ID NO: 257, HVR-H3 having the amino acid sequence of SEQ ID NO: 261, and the amino acid sequence of SEQ ID NO: 264, a VL comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 273, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 273, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, a VL comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 279, or a VL comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, -H1, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, VH comprising HVR-H3 comprising the amino acid sequence of SEQ ID NO: 261, 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 VL comprising HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278, or 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, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, SEQ ID NO: 27 a VL comprising an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 278, or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 257, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, a VL comprising an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 264, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 272, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 280, or an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 259 a VH comprising an HVR-H2 having the amino acid sequence of SEQ ID NO: 19, a VH comprising an HVR-H3 having the amino acid sequence of SEQ ID NO: 267, an HVR-L2 having the amino acid sequence of SEQ ID NO: 96, and a VL comprising an HVR-L3 having the amino acid sequence of SEQ ID NO: 97, or a VH comprising an HVR-H1 having the amino acid sequence of SEQ ID NO: 23, an HVR-H2 having the amino acid sequence of SEQ ID NO: 260, an HVR-H3 having the amino acid sequence of SEQ ID NO: 262, an HVR-L1 having the amino acid sequence of SEQ ID NO: 268, and an HVR-L2 having the amino acid sequence of SEQ ID NO: 274;and 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, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, 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-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, 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 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-L3 comprising the amino acid sequence of SEQ ID NO: 262 a VH comprising an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 267, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 276, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VH comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 268, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 277, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97; or a VL comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 23, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 260, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 262, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 267, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 96, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97.

[0014] 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; 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: 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% to the amino acid sequence of SEQ ID NO: 175; 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: 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; 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: 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;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: 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; 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: 201; 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; 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; 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; 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: 209; 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; 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; 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: 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;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: 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: 239; a VH that is 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 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172; 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; 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; 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; a VL that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 180; 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; 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; 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; a VL that is 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 that 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; 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; 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; 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;a VL that is at least 97%, or at least 99% identical; 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; 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; 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; 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; a VL that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:241; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; a VL that is at least 90%, at least 95%, at least 97% identical to the amino acid sequence of SEQ ID NO: 249;or 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; 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; % identical to the amino acid sequence of SEQ ID NO: 252, 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, 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 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. In still further 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: 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 VH comprising the amino acid sequence of SEQ ID NO: 197, VH comprising the amino acid sequence of SEQ ID NO: 199, VH comprising the amino acid sequence of SEQ ID NO: 201, VH comprising the amino acid sequence of SEQ ID NO: 203, VH comprising the amino acid sequence of SEQ ID NO: 205, VH comprising the amino acid sequence of SEQ ID NO: 207, VH comprising the amino acid sequence of SEQ ID NO: 209, VH comprising the amino acid sequence of SEQ ID NO: 234, VH comprising the amino acid sequence of SEQ ID NO: 235, VH comprising the amino acid sequence of SEQ ID NO: 236, VH comprising the amino acid sequence of SEQ ID NO: 237, VH comprising the amino acid sequence of SEQ ID NO: 238, VH comprising the amino acid sequence of SEQ ID NO: 236, VH comprising the amino acid sequence of SEQ ID NO: 237, VH comprising the amino acid sequence of SEQ ID NO: 236, VH comprising the amino acid sequence of SEQ ID NO: 237, VH comprising the amino acid sequence of SEQ ID NO: 236,VH comprising the amino acid sequence of SEQ ID NO: 239, VH comprising the amino acid sequence of SEQ ID NO: 240, VH comprising the amino acid sequence of SEQ ID NO: 240, VH comprising the amino acid sequence of SEQ ID NO: 240, VH comprising the amino acid sequence of SEQ ID NO: 240, VH comprising the amino acid sequence of SEQ ID NO: 240, or VH comprising the amino acid sequence of SEQ ID NO: 240. In still further 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: 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: 201, a VL comprising the amino acid sequence of SEQ ID NO: 202, a VL comprising the amino acid sequence of SEQ ID NO: 203, a VL comprising the amino acid sequence of SEQ ID NO: 204, a VL comprising the amino acid sequence of SEQ ID NO: 205, a VL comprising the amino acid sequence of SEQ ID NO: 206, a VL comprising the amino acid sequence of VL comprising the amino acid sequence of SEQ ID NO: 202, VL comprising the amino acid sequence of SEQ ID NO: 204, VL comprising the amino acid sequence of SEQ ID NO: 206, VL comprising the amino acid sequence of SEQ ID NO: 208, VL comprising the amino acid sequence of SEQ ID NO: 210, VL comprising the amino acid sequence of SEQ ID NO: 241, VL comprising the amino acid sequence of SEQ ID NO: 242, VL comprising the amino acid sequence of SEQ ID NO: 243, VL comprising the amino acid sequence of SEQ ID NO: 243, VL comprising the amino acid sequence of SEQ ID NO: 244, VL comprising the amino acid sequence of SEQ ID NO: 245, VL comprising the amino acid sequence of SEQ ID NO: 246, VL comprising the amino acid sequence of SEQ ID NO: 247, VL comprising the amino acid sequence of SEQ ID NO: 247, VL comprising the amino acid sequence of SEQ ID NO: 248, VL comprising the amino acid sequence of SEQ ID NO: 249, VL comprising the amino acid sequence of SEQ ID NO: 250, VL comprising the amino acid sequence of SEQ ID NO: 251, VL comprising the amino acid sequence of SEQ ID NO: 252, VL comprising the amino acid sequence of SEQ ID NO: 253, 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 (as shown in Table 1), 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: VH comprising the amino acid sequence of SEQ ID NO: 9 and VL comprising the amino acid sequence of SEQ ID NO: 170 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 171 and VL comprising the amino acid sequence of SEQ ID NO: 172 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 173 and VL comprising the amino acid sequence of SEQ ID NO: 174 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 175 and VL comprising the amino acid sequence of SEQ ID NO: 176 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 177 and 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 (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 VL comprising the amino acid sequence of SEQ ID NO: 196 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 197 and VL comprising the amino acid sequence of SEQ ID NO: 198 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 199 and VL comprising the amino acid sequence of SEQ ID NO: 200 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 201 and VL comprising the amino acid sequence of SEQ ID NO: 202 (as shown in Table 1), VH comprising the amino acid sequence of SEQ ID NO: 203 and VL comprising the amino acid sequence of SEQ ID NO: 204 (as shown in Table 1). 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 VL comprising the amino acid sequence of SEQ ID NO: 242 (as shown in Table 15), VH comprising the amino acid sequence of SEQ ID NO: 236 and VL comprising the amino acid sequence of SEQ ID NO: 243 (as shown in Table 15), 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), VH comprising the amino acid sequence of SEQ ID NO: 238 and VL comprising the amino acid sequence of SEQ ID NO: 244 (as shown in Table 15), 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). (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: 245 (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: 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).

[0015] In some embodiments, the antibody has a heavy chain that 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 that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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. a heavy chain that 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; a heavy chain that 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: 305or a heavy chain that is at least 99% identical; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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;or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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 that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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;or a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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; or a heavy chain that 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; a heavy chain that 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; a heavy chain that 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;or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; or a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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 heavy chain that 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; or a heavy chain that is at least 99% identical; a heavy chain that 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;or a heavy chain that is at least 99% identical; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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 a heavy chain that 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; a heavy chain that 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; a heavy chain that 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 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 388; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 392; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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. a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 396; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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 a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 400; a heavy chain that 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; a heavy chain that 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 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 that is at least 99% identical, a heavy chain that 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 that 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, a heavy chain that 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, a heavy chain that 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, a heavy chain that 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 a heavy chain that 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. 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 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 light chain that 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.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; a heavy chain that is at least 7%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416, and a light chain that 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, and a heavy chain that 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:416, and a light chain that 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:296, a heavy chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416, and a light chain that 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: 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;a heavy chain that is at least 97%, or at least 99%, identical to the amino acid sequence of SEQ ID NO: 416, and a light chain that 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; a heavy chain that is 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: 301; 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; a heavy chain that is at least 7%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416, and a light chain that 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, and a heavy chain that 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 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 416, and a light chain that 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; a heavy chain that 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 97%, or at least 99% identical, and a light chain that 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: 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; a heavy chain that is at least 5%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417, and a light chain that 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, and a heavy chain that 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 a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417, and a light chain that 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, and a heavy chain that 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, a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417, and a light chain that 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;a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 417, and a light chain that 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, and a heavy chain that 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 a heavy chain that 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, and a light chain that 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; a heavy chain that 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, and a light chain that 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, SEQ ID NO: 32 a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:1, and a light chain that 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: 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: 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; a light chain, a heavy chain that 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; a heavy chain that 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. a light chain that 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: 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: 328, and a heavy chain that 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: 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; a heavy chain that 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,or at least 99% identical to the amino acid sequence of SEQ ID NO:331, a heavy chain that 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 light chain that 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, a heavy chain that 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: 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. a light chain that 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, a heavy chain that 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: 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. a light chain that 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, a heavy chain that 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: 338, and a heavy chain that 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 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 339, a heavy chain that 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; , a heavy chain that 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; a heavy chain that 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 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: 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: 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; a heavy chain that 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. a light chain that is at least 99% identical, a heavy chain that 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, a heavy chain that 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,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: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: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. a light chain that 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, a heavy chain that 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 light chain that 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, a heavy chain that 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: 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: 354, a heavy chain that 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: 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,a light chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 356; a heavy chain that 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: 357; a light chain that 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, a heavy chain that 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: 359, and a heavy chain that 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 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 360, a heavy chain that 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 light chain that is 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: 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 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 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: 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: 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. a light chain that 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: 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: 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. a light chain that 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 that 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: 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. a light chain that 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: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. a heavy chain and a light chain that 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: 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: 375. a heavy chain that 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: 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; a heavy chain that is at least 99% identical to the amino acid sequence of SEQ ID NO: 420, and a light chain that 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, and a heavy chain that 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,or a heavy chain that is at least 99% identical, and a light chain that 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: 326; and 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: 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: 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 light chain that 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 that 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: 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: 42 a light chain that 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; a heavy chain that 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: 332; a light chain that 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: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, a heavy chain that 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, a heavy chain that 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, a heavy chain that 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. a heavy chain and a light chain that 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: 338. a heavy chain that 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 that is at least 99% identical to the amino acid sequence of SEQ ID NO: 421, and a light chain that 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, and a heavy chain that 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,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: 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; a heavy chain that 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 7%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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; a heavy chain that 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: 346 a heavy chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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: 422;a heavy chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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; a heavy chain that 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: 352. a heavy chain that is at least 5%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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; a heavy chain that 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, a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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; a heavy chain that 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: 356 a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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,a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 422, and a light chain that 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, and a heavy chain that 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. a heavy chain that 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, and a light chain that 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; a heavy chain that 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, and a light chain that 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, a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:8, and a light chain that 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: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;a heavy chain that 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; a heavy chain that is at least 97%, or at least 99% identical, and a light chain that 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: 333; a heavy chain that is at least 5%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423, and a light chain that 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; a heavy chain that 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 a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423, and a light chain that 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; a heavy chain that 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: 337 a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423, and a light chain that 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;a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 423, and a light chain that 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, and a light chain that 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 a heavy chain that 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, and a light chain that 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: 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: 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: 423, and a light chain that 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, SEQ ID NO: 34 a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:5, and a light chain that 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: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;a heavy chain that 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; a heavy chain that 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. a light chain, a heavy chain that 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; a heavy chain that 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; a light chain that 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, a heavy chain that 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 light chain that 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, a heavy chain that 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: 354, and a heavy chain that 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,or at least 99% identical to the amino acid sequence of SEQ ID NO: 355; a heavy chain that 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; a heavy chain that 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; a light chain that 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, a heavy chain that 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: 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. a light chain that 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, a heavy chain that 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: 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 light chain that 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, a heavy chain that 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 light chain that is 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: 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: 364; a light chain that 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: 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: 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 a light chain that is 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: 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: 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. a light chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 369, a heavy chain that 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: 370, and a light chain that is 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 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 371; a heavy chain that 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: 372, a heavy chain that 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: 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: 374, a heavy chain that 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: 375, and a heavy chain that 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: 376, a heavy chain that 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: 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. a light chain that 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, a heavy chain that 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: 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.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: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: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: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 light chain that 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: 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: 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: 330, a heavy chain that 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: 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. a light chain that 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, a heavy chain that 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: 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,a light chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 334; a heavy chain that 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; a heavy chain that 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. a light chain that 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, a heavy chain that 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 light chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 338, a heavy chain that 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: 426. a light chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 340, a heavy chain that 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: 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,a light chain that is 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: 342; a light chain that 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: 343; a light chain that 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, a heavy chain that 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: 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. a light chain that 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: 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 light chain that 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: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: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, a heavy chain that 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 and a light chain that 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: 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; a heavy chain that 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: 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; a heavy chain that is at least 99% identical to the amino acid sequence of SEQ ID NO: 427, and a light chain that 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, and a heavy chain that 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,or a heavy chain that is at least 99% identical to the amino acid sequence of SEQ ID NO: 427, and a light chain that 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 ... a light chain that 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: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:396. a heavy chain, and a light chain that 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: 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; a heavy chain that 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: 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; a heavy chain that is at least 99% identical to the amino acid sequence of SEQ ID NO: 428, and a light chain that 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; a heavy chain that 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,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; a heavy chain that is at least 7%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428, and a light chain that 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; a heavy chain that 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: 406 a heavy chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:428, and a light chain that 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: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; a heavy chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428, and a light chain that 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: 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;a heavy chain that is at least 97%, or at least 99% identical, and a light chain that 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: 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; a heavy chain that is at least 5%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428, and a light chain that 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, and a heavy chain that 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, a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 428, and a light chain that 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; a heavy chain that 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: 398, a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 429, and a light chain that 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; a heavy chain that 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: 400;a heavy chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 429, and a light chain that 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: 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; a heavy chain that 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, and a light chain that 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: 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; a heavy chain that 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, and a light chain that 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:6, and a light chain that 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: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: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; a heavy chain that 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; a light chain, a heavy chain that 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; a heavy chain that 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; a light chain that 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, a heavy chain that 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: 399, and a heavy chain that 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:400, a heavy chain that 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,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: 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: 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: 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: 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; a heavy chain that 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, and a light chain that 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: 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; a heavy chain that 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, and a light chain that 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: 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; a heavy chain that 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; a heavy chain that 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;a heavy chain that 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 light chain, a heavy chain that 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; a heavy chain that 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. a light chain that 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, a heavy chain that 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: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. a light chain that 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; a heavy chain that 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;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; and a light chain that 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:406; a light chain that 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: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 light chain that 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, a heavy chain that 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: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. a light chain that 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, a heavy chain that 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: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,a light chain that is at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:399; a heavy chain that 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:400; a light chain that 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, a heavy chain that 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 light chain that 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 heavy chain that 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 light chain that is 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: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 light chain that is 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: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: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,a light chain that is 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: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: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. a light chain that 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, a heavy chain that 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: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. a light chain that 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, a heavy chain that 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: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. a light chain that 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 heavy chain that 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 light chain that 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:433, a light chain that 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 heavy chain that 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 light chain that is 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: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:405; a light chain that 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: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: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. a light chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:408, a heavy chain that 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 light chain that is at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 410, a heavy chain that 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 a heavy chain that 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.

[0016] In some embodiments, the disclosure herein provides 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, SEQ ID NO:298, or a heavy chain comprising the amino acid sequence of 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: 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 light 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: 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: 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; 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: 418, SEQ ID NO: 344 or SEQ ID NO: a heavy chain comprising the amino acid sequence of 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: 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, SEQ ID NO: 372 or a heavy chain comprising the amino acid sequence of SEQ ID NO: 373 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: 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: 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: 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; 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: a heavy chain comprising the amino acid sequence of 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: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: 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: 423; 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, SEQ ID NO: 356 or a heavy chain comprising the amino acid sequence of 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: 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: 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: 337 and a light chain comprising the amino acid sequence of SEQ ID NO: 426; SEQ ID NO: 338; or a heavy chain comprising the amino acid sequence of 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: 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, SEQ ID NO: 402 or SEQ ID NO: a heavy chain comprising the amino acid sequence of SEQ ID 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: 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; 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, SEQ ID NO: 412 or SEQ ID NO: a heavy chain comprising the amino acid sequence of 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: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: 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: 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 a heavy chain comprising the amino acid sequence of 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: 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: 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: 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: 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; The present invention 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: 408 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: 433.

[0017] In still further embodiments, the disclosure herein provides 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, GPN-98, GPN-99, GPN-100, GPN-101, GPN-102, GPN-103, GPN-104, GPN-105, GPN-106, GPN-107, GPN-108, GPN-109, GPN-110, GPN-111, GPN-112, GPN-113, GPN-114, GPN-115, GPN-116, GPN-117, GPN-118, GPN-119, GPN-120, GPN-121, GPN-122, GPN-123, GPN-124, GPN-125, GPN-126, GPN-127, GPN-128, GPN-129, GPN-130, GPN-131, GPN-132, GPN-133 and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of any one of 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 is selected from the group consisting of 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 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 is selected from the group consisting of antibody 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,It comprises the VH and / or VL of any one of 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 (shown in Table 2), and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-01 (shown in Table 3), or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-03 (shown in Table 2), and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-03 (shown in Table 3). or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-06 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-06 (shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-07 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-07 (shown in Table 3). ), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-08 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-08 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-09 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-09 (shown in Table 3), or or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-11 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-11 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-22 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-22 (shown in Table 3); or the VHor the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-24 (shown in Table 2), and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-24 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-25 (shown in Table 2), and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-25 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-26 (shown in Table 2). wherein the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-26 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-30 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-30 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-31 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-31 (shown in Table 3). or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-33 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-33 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-34 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-34 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-35 or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-37 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-37 (shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-38 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-38.and HVR-L3 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-41 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-41 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-42 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-42 (shown in Table 3), or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-43, or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-48 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-48 (shown in Table 3); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-52 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-52. or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-61 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-61 (shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-65 (shown in Table 2) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-65 (shown in Table 3); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-8 or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-81 (shown in Table 17); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-82 (shown in Table 16); and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-82 (shown in Table 17); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-83 (shown in Table 16); and the VL comprisesor the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-83 (shown in Table 17); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-84 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-84 (shown in Table 17); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-85 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-85 (shown in Table 17). or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-86 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-86 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-87 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-87 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-88 (shown in Table 18). or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-89 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-89 (shown in Table 17); or the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-90 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-90. or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-91 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-91 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-92 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-92 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-93,or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-94 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-94 (shown in Table 17). or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-95 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-95 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-96 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-96 (shown in Table 17). or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-97 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-97 (shown in Table 17); or wherein the VH comprises HVR-H1, HVR-H2, and HVR-H3 of antibody GPN-98 (shown in Table 16) and the VL comprises HVR-L1, HVR-L2, and HVR-L3 of antibody GPN-98 (shown in Table 17).

[0018] In some cases, the antibodies herein antagonize GPNMB activity. In some embodiments, the anti-GPNMB antibodies modulate expression of activation surface markers in myeloid cells, increase cell surface expression of PD-L1 in human macrophages, increase cell surface expression of CD40 in human macrophages, increase cell surface expression of CD80 in human macrophages, modulate lysosomal function in myeloid cells, increase glucocerebrosidase activity in human macrophages, decrease cell surface expression of GPNMB in human macrophages, alter interferon pathway gene expression patterns 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, and increase serum levels of IL-12p40. and increases the level of CCL5 in serum; is a GPNMB ligand blocking antibody; is a non-blocking antibody; antagonizes GPNMB activity independent of ligand blocking activity; antagonizes GPNMB activity in vivo; binds to GPNMB expressed on the cell surface; overcomes the decrease in glucocerebrosidase activity associated with reduced progranulin levels; reduces GPNMB expression levels in cells, optionally macrophages; reduces LAMP2 expression levels in cells, optionally macrophages, monocytes, or neutrophils; inhibits or reduces inflammasome activation; inhibits IL-1β expression or release; reduces neuroinflammation; reduces expression of C1q, GFAP, IBA1, and CTSD associated with neuroinflammation; and / or reduces lysosomal stress.

[0019] In some embodiments, the antibody binds to human GPNMB, mouse GPNMB, cynomolgus GPNMB, both human GPNMB and mouse GPNMB, or human GPNMB, mouse GPNMB, and cynomolgus 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, or about 0.14 to about 0.65 nM, and to mouse GPNMB with an affinity of about 0.18 nM to about 0.44 nM.

[0020] In some cases, the antibody is a monoclonal antibody, a humanized antibody, an antigen-binding fragment, such as a Fab, Fab', Fab'-SH, F(ab')2, Fv, or scFv fragment, or a bispecific or multispecific antibody. In some cases, the antibody is of the IgG class, IgM class, or IgA class, such as an antibody of a human IgG1, IgG2, IgG3, or IgG4 isotype, or a mouse IgG1 or IgG2 isotype. In some cases, the antibody binds to an inhibitory Fc receptor, 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 is 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, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, The antibody comprises one or more amino acid substitutions in an amino acid residue in the Fc region selected from the group consisting of 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 residues are numbered according to EU numbering. In some cases, 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, where residue numbering 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 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, where residue numbering is according to EU numbering.

[0021] 55. The antibody of any one of claims 1-54, 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.

[0022] The present disclosure also relates to pharmaceutical compositions comprising an anti-GPNMB antibody described herein and a pharmaceutically acceptable carrier, as well as isolated nucleic acids comprising a nucleic acid sequence encoding an anti-GPNMB antibody described herein, isolated vectors comprising the nucleic acid, and isolated host cells comprising the nucleic acid or vector. The present disclosure further relates to methods of producing an anti-GPNMB antibody, comprising culturing host cells to produce the antibody, and optionally further recovering the antibody produced by the cells.

[0023] The present disclosure also relates to methods of treating cancer in a subject in need thereof, comprising administering to the individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody herein, thereby treating the cancer. In some cases, the method further comprises administering one or more therapeutic agents, such as a checkpoint inhibitor, such as a PD1, PD-L1, and PD-L2 inhibitor, such as an anti-PD-L1 antibody, an anti-PD-L2 antibody, and an anti-PD-1 antibody. In some cases, the cancer is 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. In some cases, the cancer is glioblastoma multiforme, bladder cancer, esophageal cancer, or triple-negative breast cancer.

[0024] The present disclosure further relates to a method of treating a neurodegenerative disease or disorder in a subject in need thereof, comprising administering to the individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody herein, thereby treating the disease or disorder. In some cases, the disease or disorder is selected from Parkinson's disease, Alzheimer's disease, and ALS.

[0025] The present disclosure also relates to a method of treating a lysosomal storage disease or disorder in a subject in need thereof, comprising administering to the individual in need thereof a therapeutically effective amount of an anti-GPNMB antibody herein, thereby treating the disease or disorder. In some cases, the lysosomal storage disease is Gaucher disease.

[0026] The present disclosure also relates to methods for detecting the presence of GPNMB in a sample in vitro or in an individual, the methods comprising the anti-GPNMB antibodies herein. In some cases, the methods further comprise quantifying the antigen-bound anti-GPNMB antibody.

[0027] It is understood that one, some, or all of the features of the various embodiments described herein may 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 explained in the detailed description below. In some aspects, provided herein are methods for detecting GPNMB in a sample, comprising contacting the sample with any of the anti-GPNMB antibodies described herein.

[0028] This U.S. provisional application contains at least one drawing executed in color. If a nonprovisional or PCT application claiming priority to and incorporating the subject matter of this provisional application is later published, copies of this provisional application with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [Brief explanation of the drawings]

[0029] [Figure 1] 1 shows the amino acid alignment of human (SEQ ID NO: 1), mouse (SEQ ID NO: 435), and cynomolgus monkey (SEQ ID NO: 434) GPNMB. [Figure 2A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure bind to Freestyle293 cells expressing human GPNMB and B16F10 cells expressing mouse GPNMB, respectively. [Figure 2B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure bind to Freestyle293 cells expressing human GPNMB and B16F10 cells expressing mouse GPNMB, respectively. [Figure 2C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure bind to U937 cells expressing GPNMB. [Figure 3A] 1 shows data showing titration curves of anti-GPNMB antibodies of the present disclosure binding to Freestyle293 cells expressing human GPNMB and B16F10 cells expressing mouse GPNMB, respectively. [Figure 3B]1 shows data showing titration curves of anti-GPNMB antibodies of the present disclosure binding to Freestyle293 cells expressing human GPNMB and B16F10 cells expressing mouse GPNMB, respectively. [Figure 4A] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4B] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4C] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4D] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4E] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4F] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4G] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4H] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4I] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 4J] 1 presents data showing the binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to various cell types. [Figure 5A] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure in blocking or enhancing binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to SVEC cells. [Figure 5B] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure in blocking or enhancing binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to SVEC cells. [Figure 5C] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure in blocking or enhancing binding of soluble murine GPNMB-Fc or soluble human GPNMB-Fc polypeptide constructs to SVEC cells. [Figure 6A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6D] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6E] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6F] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6G] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increase cell surface expression of PDL1, CD40, and CD80 on macrophages. [Figure 6H]1 presents data showing the effect of JAK kinase inhibitors on the increase in cell surface PDL1 expression induced by anti-GPNMB antibodies of the present disclosure. [Figure 7] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure on increasing glucocerebrosidase activity in macrophages. [Figure 8] 1 presents data showing that anti-GPNMB antibodies of the present disclosure induce cell surface GPNMB internalization. [Figure 9] 1 shows data showing binning results for anti-GPNMB antibodies of the disclosure that bind to GPNMB. [Figure 10] 1 shows data showing various GPNMB chimeric polypeptide constructs containing human and mouse GPNMB domains. [Figure 11A]

[0023] Figure 1 shows data demonstrating that genetically depleting GPNMB in M1 and M2 polarized macrophages resulted in an increase in the interferon response pathway of chemokines and cytokines. [Figure 11B]

[0023] Figure 1 shows data demonstrating that genetically depleting GPNMB in M1 and M2 polarized macrophages resulted in an increase in the interferon response pathway of chemokines and cytokines. [Figure 11C]

[0023] Figure 1 shows data demonstrating that genetically depleting GPNMB in M1 and M2 polarized macrophages resulted in an increase in the interferon response pathway of chemokines and cytokines. [Figure 12A] 1 presents data showing the effect of anti-GPNMB antibody GPN-61 on differential gene expression of various genes related to the interferon signaling pathway in human macrophages. [Figure 12B] 1 presents data showing the effect of anti-GPNMB antibody GPN-61 on differential gene expression of various genes related to the interferon signaling pathway in human macrophages. [Figure 13] 1 shows data demonstrating reduced tumor growth in GPNMB knockout and GPNMB heterozygous knockout mice in an in vivo mouse tumor model. [Figure 14A] 1 shows data showing GPNMB expression in macrophages and monocytes as measured by scRNAseq analysis. [Figure 14B] 1 shows data showing GPNMB expression in macrophages and monocytes as measured by scRNAseq analysis. [Figure 14C] 1 shows data demonstrating that GPNMB heterozygosity resulted in a decreased number of suppressor-like monocytes (myeloid-derived suppressor cells, CD14+) from cluster 2. [Figure 14D] Data are shown showing that GPNMB heterozygosity resulted in differential gene expression patterns in cluster 3 (CD8+ T cells), cluster 0 (C1QC+ macrophages), and cluster 9 (proliferating T cells), respectively. [Figure 14E] Data are shown showing that GPNMB heterozygosity resulted in differential gene expression patterns in cluster 3 (CD8+ T cells), cluster 0 (C1QC+ macrophages), and cluster 9 (proliferating T cells), respectively. [Figure 14F] Data are shown showing that GPNMB heterozygosity resulted in differential gene expression patterns in cluster 3 (CD8+ T cells), cluster 0 (C1QC+ macrophages), and cluster 9 (proliferating T cells), respectively. [Figure 15A] 1 shows data demonstrating the reduction of tumor volume of anti-GPNMB antibody GPN-61 in vivo in a mouse tumor model. [Figure 15B] 1 shows data demonstrating the reduction of tumor volume of anti-GPNMB antibody GPN-61 in vivo in a mouse tumor model. [Figure 16A] 1 shows data demonstrating reduced glucocerebrosidase activity in granulocytes and monocytes / macrophages in wild-type and progranulin knockout mice, respectively. [Figure 16B] 1 shows data demonstrating reduced glucocerebrosidase activity in granulocytes and monocytes / macrophages in wild-type and progranulin knockout mice, respectively. [Figure 16C]10 shows data showing that treatment of progranulin knockout mice with the anti-GPNMB antibody GPN-61 resulted in higher glucocerebrosidase activity in monocytes compared to that observed in GRN− / − mice treated with an isotype control antibody. [Figure 17] Data are presented showing that treatment of either wild-type or progranulin knockout mice with the anti-GPNMB antibody GPN-61 resulted in elevated levels of IL-12p40 and CCL5 in serum, respectively, compared to those observed in animals treated with an isotype control antibody. [Figure 18] Data are shown showing heat maps comparing differentially expressed genes from GPNMB knockout mice (WT-KO), GPNMB knockout mice treated with CBE (Gpnmb KO CBE), and wild-type mice treated with CBE (Gpnmb WT CBE). [Figure 19A] 1 shows data showing a comparison of selected antiviral, interferon-related genes showing differential expression (Stat2, Irf9, Cxcl16, and Ifit3b) in wild-type (WT) and GPNMB knockout mice (Gpnmb KO) treated with CBE. [Figure 19B] 1 shows data showing a comparison of selected antiviral, interferon-related genes showing differential expression (Stat2, Irf9, Cxcl16, and Ifit3b) in wild-type (WT) and GPNMB knockout mice (Gpnmb KO) treated with CBE. [Figure 19C] 1 shows data showing a comparison of selected antiviral, interferon-related genes showing differential expression (Stat2, Irf9, Cxcl16, and Ifit3b) in wild-type (WT) and GPNMB knockout mice (Gpnmb KO) treated with CBE. [Figure 19D]1 shows data showing a comparison of selected antiviral, interferon-related genes showing differential expression (Stat2, Irf9, Cxcl16, and Ifit3b) in wild-type (WT) and GPNMB knockout mice (Gpnmb KO) treated with CBE. [Figure 20A] Data are presented showing increased expression of complement component 1q (C1q), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA1), and cathepsin D (CatD) in the cortex of wild-type or GPNMB knockout mice treated or not with conduritol B-epoxide (CBE). [Figure 20B] Data showing the relative intensities of the expressed proteins from Figure 20A are shown. [Figure 20C] Data showing the relative intensities of the expressed proteins from Figure 20A are shown. [Figure 20D] Data showing the relative intensities of the expressed proteins from Figure 20A are shown. [Figure 20E] Data showing the relative intensities of the expressed proteins from Figure 20A are shown. [Figure 20F] 1 shows data demonstrating increased serum C-X-C motif chemokine ligand 1 (CXCL1) in wild-type or GPNMB knockout mice treated with or without CBE. [Figure 21] Figure 21A shows data demonstrating increased expression of IL-1β in human macrophages stimulated with LPS plus nigericin (to activate inflammasomes), and Figure 21B shows data demonstrating that anti-GPNMB antibodies of the present disclosure inhibited inflammasome activation in human macrophages, as measured by changes in IL-1β expression. [Figure 22] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced expression of IL-1β in human macrophages after inflammasome activation by LPS plus nigericin. [Figure 23]1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in reducing inflammasome activation in human macrophages. [Figure 24A] 1 shows data demonstrating an increased lysosomal stress response (as measured by Lysotracker fluorescent staining) in human macrophages stimulated with rapamycin. [Figure 24B] 1 shows data demonstrating an increased lysosomal stress response (as measured by Lysotracker fluorescent staining) in human macrophages stimulated with rapamycin. [Figure 24C] 1 shows data demonstrating differences in the lysosomal stress response in murine bone marrow-derived macrophages obtained from wild-type or GPNMB knockout mice in the presence or absence of rapamycin. [Figure 24D] 1 shows data demonstrating differences in the lysosomal stress response in murine bone marrow-derived macrophages obtained from wild-type or GPNMB knockout mice in the presence or absence of rapamycin. [Figure 24E] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure on the lysosomal stress response in human macrophages. [Figure 24F] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure on the lysosomal stress response in human macrophages. [Figure 25A] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure were effective in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 25B] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure were effective in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 25C] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure were effective in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 25D]1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure were effective in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 26A] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 26B] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 26C] 1 presents data showing the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in reducing rapamycin-induced lysosomal stress in human macrophages. [Figure 27A] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure increase expression of PDL1 and CD40 in human macrophages. [Figure 27B] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure increase expression of PDL1 and CD40 in human macrophages. [Figure 27C] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure increase expression of PDL1 and CD40 in human macrophages. [Figure 27D] 1 presents data showing that affinity matured anti-GPNMB antibodies of the present disclosure increase expression of PDL1 and CD40 in human macrophages. [Figure 28A] 1 shows data demonstrating the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in increasing the expression of PDL1 and CD40 in human macrophages. [Figure 28B] 1 shows data demonstrating the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in increasing the expression of PDL1 and CD40 in human macrophages. [Figure 28C]1 shows data demonstrating the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in increasing the expression of PDL1 and CD40 in human macrophages. [Figure 28D] 1 shows data demonstrating the effect of anti-GPNMB antibodies of the present disclosure with different Fc variants in increasing the expression of PDL1 and CD40 in human macrophages. [Figure 29A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure with different Fc variants increase GCase activity in human macrophages. [Figure 29B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure with different Fc variants increase GCase activity in human macrophages. [Figure 29C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure with different Fc variants increase GCase activity in human macrophages. [Figure 30A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 30B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 30C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 31A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 31B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 31C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced the expression of the mature form of GPNMB protein in human macrophages. [Figure 32A]1 presents data showing that the anti-GPNMB antibodies GPN-41 and GPN-65 reduced the expression of both mature and immature forms of the GPNMB protein in human macrophages. [Figure 32B] 1 presents data showing that the anti-GPNMB antibodies GPN-41 and GPN-65 reduced the expression of both mature and immature forms of the GPNMB protein in human macrophages. [Figure 32C] 1 presents data showing that the anti-GPNMB antibodies GPN-41 and GPN-65 reduced the expression of both mature and immature forms of the GPNMB protein in human macrophages. [Figure 33A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced LAMP-2 levels in splenocytes, macrophages, monocytes, and neutrophils. [Figure 33B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure reduced LAMP-2 levels in splenocytes, macrophages, monocytes, and neutrophils. [Figure 34A] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increased GCase activity in primary microglia, splenic macrophages, neutrophils, monocytes, and macrophages. [Figure 34B] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increased GCase activity in primary microglia, splenic macrophages, neutrophils, monocytes, and macrophages. [Figure 34C] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increased GCase activity in primary microglia, splenic macrophages, neutrophils, monocytes, and macrophages. [Figure 34D] 1 presents data showing that anti-GPNMB antibodies of the present disclosure increased GCase activity in primary microglia, splenic macrophages, neutrophils, monocytes, and macrophages. DETAILED DESCRIPTION OF THE INVENTION

[0030] Detailed Description of the Disclosure The present disclosure relates to anti-GPNMB antibodies (e.g., 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.

[0031] The techniques and procedures described or referenced herein are generally well understood and commonly employed by those of skill in the art using conventional methodologies, such as, for example, widely used methodologies described in: Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd edition (2001), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (F.M. Ausubel, et al., eds., (2003); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000).

[0032] definition The terms "GPNMB" or "GPNMB polypeptide" or "GPNMB protein" are used interchangeably herein and, unless otherwise specified, refer to any native GPNMB from any vertebrate source, including mammals such as primates (e.g., humans and cynomolgus monkeys (cynos)) and rodents (e.g., mice and rats). GPNMB is also referred to as osteoactivin (rat orthologue), dendritic cell-heparin integrin ligand (DC-HIL, mouse orthologue), or hematopoietic growth factor-inducible neurokinin type 1 (HGFIN). In some embodiments, the term encompasses both wild-type 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 resulting from processing within cells. In some embodiments, the 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.

[0033] The terms "anti-GPNMB antibody," "antibody that binds GPNMB," and "antibody that specifically binds GPNMB" refer to an antibody that can bind GPNMB with sufficient affinity such that the antibody is useful as a diagnostic and / or therapeutic agent targeting GPNMB. In one embodiment, the extent of binding of an anti-GPNMB antibody to an unrelated, non-GPNMB polypeptide is less than about 10% of the binding of the antibody to GPNMB, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, an antibody that binds GPNMB has an affinity of less than 1 μM, less than 100 nM, less than 10 nM, less than 1 nM, less than 0.1 nM, less than 0.01 nM, or less than 0.001 nM (e.g., 10 -8 M or less, e.g., 10 -8 ~10 -13 M, e.g., 10 -9 M~10 -13 M) In certain embodiments, the anti-GPNMB antibody binds to an epitope of GPNMB that is conserved among GPNMB from different species.

[0034] With respect to the binding of an antibody to a target molecule, the term "specific binding" to or "specifically binds to" or "is specific for" a particular polypeptide or epitope on a particular polypeptide target refers to binding that is measurably different from non-specific interactions. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule. For example, specific binding can be determined by competition with a control molecule similar to the target, e.g., an excess of unlabeled target. In this case, specific binding is indicated when the binding of the labeled target to the probe is competitively inhibited by the excess of unlabeled target. As used herein, the term "specific binding" to or "specifically binds to" or "is specific for" a particular polypeptide or epitope on a particular polypeptide target refers to binding that is measurably different from non-specific interactions. -4 M or less, 10 -5 M or less, 10 -6 M or less, 10 -7 M or less, 10 -8 M or less, 10 -9 M or less, 10 -10 M or less, 10 -11 M or less, 10 -12 KD for any target less than or equal to M, or 10 -4 M~10 -6 M or 10 -6 M~10 -10 M or 10 -7 M~10 -9 Affinity can be exhibited by a molecule having a KD in the range of M. As will be understood by those skilled in the art, affinity and KD values are inversely related. High affinity for an antigen is measured by a low KD value. In one embodiment, the term "specific binding" refers to binding of a molecule to a particular polypeptide or an epitope on a particular polypeptide without substantially binding to any other polypeptides or polypeptide epitopes.

[0035] The term "immunoglobulin" (Ig) is used interchangeably herein with "antibody." The term "antibody" is used herein in the broadest sense to specifically encompass monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), such as those formed from at least two intact antibodies, and antigen-binding antibody fragments, so long as they exhibit the desired biological activity.

[0036] "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 contains at one end a variable domain (V H ), followed by several constant domains. Each light chain has at one end a variable domain (V L ), and at the other end a constant domain, with the light chain constant domain aligned with the first constant domain of the heavy chain and the light chain variable domain aligned with the heavy chain variable domain. Particular amino acid residues are believed to form an interface between the light-chain variable domain and the heavy-chain variable domain.

[0037] For the structure and properties of different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th Ed., Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, page 71 and Chapter 6.

[0038] The light chains of 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. Depending on the amino acid sequence of the constant domain (CH) of the heavy chain, immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, each with heavy chains designated alpha ("α"), delta ("δ"), epsilon ("ε"), gamma ("γ"), and mu ("μ"). The gamma and alpha 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 are generally described in, for example, Abbas et al., Cellular and Molecular Immunology, 4 th ed.(WBSaunders Co.,2000).

[0039] The "variable region" or "variable domain" of an antibody, such as the anti-GPNMB antibody of the present disclosure, refers to the amino-terminal domains of the heavy or light chain of the antibody. The heavy and light chain variable domains are referred to as "V H " and "V L These domains are generally the most variable parts of an antibody (compared to other antibodies of the same class) and contain the antigen-binding sites.

[0040] The term "variable" refers to the fact that the sequences of certain segments of the variable domains vary significantly among antibodies, such as the anti-GPNMB antibodies of the present disclosure. The variable domains mediate antigen binding and define the specificity of a particular antibody for a particular antigen. However, variability is not uniformly distributed throughout the span of the variable domains. Instead, it is concentrated in three segments called hypervariable regions (HVRs) in both the light-chain and heavy-chain variable domains. The more highly conserved portions of the variable domains are called framework regions (FRs). Naturally occurring heavy- and light-chain variable domains each contain four FR regions, which primarily adopt a beta-sheet structure connected by three HVRs that form loops connecting the beta-sheet structure and, in some cases, form part of the beta-sheet structure. The HVRs of each chain are held together in close proximity by the FR regions and, together with the HVRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Immunological Interest, Fifth Edition, National Institutes 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 in antibody-dependent cellular toxicity.

[0041] As used herein, the term "monoclonal antibody" refers to an antibody, such as a monoclonal anti-GPNMB antibody of the present disclosure, obtained from a population of substantially homogeneous antibodies; i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations and / or post-translational modifications (e.g., isomerization, amidation, etc.) that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, monoclonal antibodies are advantageous in that they are synthesized by hybridoma culture, uncontaminated by other immunoglobulins. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies to be used in accordance with the present invention may be made by a variety of techniques, including, but not limited to, one or more of the following methods: immunization of animals, including, but not limited to, rats, mice, rabbits, guinea pigs, hamsters, and / or chickens, with one or more of DNA(s), virus-like particles, polypeptide(s), and / or cell(s); hybridoma methods; B-cell cloning methods; recombinant DNA methods; and techniques for producing human or human-like antibodies in animals that possess some or all of the human immunoglobulin loci or genes encoding human immunoglobulin sequences.

[0042] The terms "full length antibody," "intact antibody," or "whole antibody" are used interchangeably to refer to an antibody in a substantially intact form, e.g., an anti-GPNMB antibody, as opposed to an antibody fragment. Specifically, full length antibodies include those having two light chains and two heavy 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, an intact antibody may have one or more effector functions.

[0043] The term "monovalent antibody" or "mono-arm antibody" refers to an antibody that has a single antigen-binding recognition domain specific for a target antigen (i.e., the antibody contains 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" with respect to a target contains no more than one antigen-binding domain with respect to that target.

[0044] "Antibody fragment" refers to a molecule other than an intact antibody that contains 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. Pat. No. 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.

[0045] 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 (e.g., the hypervariable region (HVR)) that contains the amino acid residues that confer on the antibody molecule its specificity for an antigen.

[0046] 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, a name reflecting its ability to be readily crystallized. The Fab fragment contains the variable region domain of the heavy chain (V H ) and the first constant domain of one heavy chain (C H Fab fragments are composed of an entire light chain with a single F(ab')2 fragment containing one or more cysteines from the antibody hinge region. Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')2 fragment which roughly corresponds to two disulfide-linked Fab fragments with different antigen-binding activities and is still capable of antigen cross-linking. The Fab' fragment contains one or more cysteines from the antibody hinge region, C(ab')2. HF(ab')2 antibody fragments differ from Fab fragments by having a few additional residues at the carboxy terminus of one domain. Fab'-SH is the designation used herein for Fab' in which the cysteine residue(s) in the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical bonds for antibody fragments are also known.

[0047] The Fc fragment contains the carboxy-terminal portions of both heavy chains held together by disulfides. The effector functions of an antibody are determined by sequences in the Fc region, which is also recognized by Fc receptors (FcRs) found on certain types of cells.

[0048] "Functional fragments" of antibodies, such as the anti-GPNMB antibodies of the present disclosure, comprise a portion of an intact antibody, generally comprising the antigen-binding or variable region of the intact antibody, or the Fc region of the antibody that retains or has altered FcR binding ability. Examples of antibody fragments include linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0049] The term "diabody" refers to a diabody that is a fragment of a V fusion protein that achieves inter-chain but not intra-chain variable domain pairing, thereby resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. H Domains and V L This refers to small antibody fragments prepared by constructing scFv fragments with short linkers (approximately 5-10 residues) between the domains. Bispecific diabodies are small antibody fragments prepared by constructing scFv fragments with short linkers (approximately 5-10 residues) between the domains. H and V L It is a heterodimer of two "crossover" sFv fragments in which the domains are present on different polypeptide chains.

[0050] As used herein, "chimeric antibody" refers to antibodies (immunoglobulins), such as the chimeric anti-GPNMB antibodies of the present disclosure, in which a portion of the heavy and / or light chain is identical to or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical to or homologous to corresponding sequences in antibodies 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). Chimeric antibodies of interest herein include PRIMATIZED® antibodies, in which the antigen-binding region of the antibody is derived from an antibody produced, for example, by immunizing macaque monkeys with the antigen of interest. As used herein, "humanized antibody" is used as a subset of "chimeric antibody."

[0051] A "humanized" form of a non-human (e.g., murine) antibody, e.g., a humanized form of an anti-GPNMB antibody of the present disclosure, is a chimeric antibody comprising amino acid residues from non-human HVRs and human FRs. In certain embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, with all or substantially all of its HVRs (e.g., CDRs) corresponding to those of a non-human antibody and all or substantially all of its FRs corresponding to those of a human antibody. A humanized antibody may optionally comprise at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has undergone humanization.

[0052] A "human antibody" is one having an amino acid sequence corresponding to that of an antibody, such as the anti-GPNMB antibody of the present disclosure, that has been produced by a human and / or that has been produced using any of the techniques for producing human antibodies disclosed herein. This definition of human antibody specifically excludes humanized antibodies that contain 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 antigen to transgenic animals, e.g., immunized xeno-mouse, that have been engineered to produce such antibodies in response to antigen challenge but whose endogenous gene loci have been disabled, and can also be generated by human B-cell hybridoma technology.

[0053] The terms "hypervariable region," "HVR," or "HV," as used herein, refer to the regions of an antibody variable domain, such as those of an anti-GPNMB antibody of the present disclosure, that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies contain six HVRs (HVs). H (H1, H2, H3) and V L HVRs are composed of three heavy chains (L1, L2, and L3). In natural antibodies, H3 and L3 show the most diversity among the six HVRs, and H3 in particular is thought to play a unique role in conferring excellent specificity to antibodies. Naturally occurring camelid antibodies, which consist only of heavy chains, are functional and stable in the absence of light chains.

[0054] A number of HVR delineations are used herein and are encompassed herein. In some embodiments, HVRs may be Kabat complementarity-determining regions (CDRs), which are based on sequence variability and are the most commonly used (Kabat et al., supra). In some embodiments, HVRs may be Chothia CDRs. Chothia instead refers to the location of structural loops (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 in 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. Residues for each of these HVRs are shown below. TIFF2025527204000002.tif107165

[0055] HVRs may include "extended HVRs" as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) of VL, and 26-35 (H1), 50-65 or 49-65 (preferred embodiment) (H2), and 93-102, 94-102, or 95-102 (H3) of VH. The variable domain residues are numbered according to Kabat et al. (supra) for each of these extended HVR definitions.

[0056] "Framework" or "FR" residues are those variable domain residues other than the HVR residues as herein defined.

[0057] As used herein, an "acceptor human framework" refers to a V-framework derived from a human immunoglobulin framework or a human consensus framework. L or V HA framework comprising the amino acid sequence of a framework. An acceptor human framework "derived" from a human immunoglobulin framework or a human consensus framework may comprise the same amino acid sequence or may contain 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 the VH, those preferred changes occur at only three, two, or one of positions 71H, 73H, and 78H; for example, the amino acid residues at those positions may be 71A, 73T, and / or 78A. In one embodiment, the VL acceptor human framework comprises a VL. L It is identical in sequence to a human immunoglobulin framework sequence or a human consensus framework sequence.

[0058] The "human consensus framework" is based on human immunoglobulin V L or V H A framework representing the most commonly occurring amino acid residues in a selection of framework sequences. Generally, human immunoglobulin V L or V H The selection of sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is as set forth in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991). L Examples for V include subgroups that may be subgroups kappa I, kappa II, kappa III, or kappa IV of Kabat et al., supra. H For example, the subgroup may be subgroup I, subgroup II, or subgroup III of Kabat et al., supra.

[0059] For example, an "amino acid modification" at a particular position in an anti-GPNMB antibody of the present disclosure refers to a substitution or deletion of the particular residue, or an insertion of at least one amino acid residue adjacent to the particular residue. An insertion "adjacent to" a particular residue refers to an insertion within one to two residues of the particular residue. The insertion may be N-terminal or C-terminal to the specified residue. A preferred amino acid modification herein is a substitution.

[0060] An "Fv" is the minimum antibody fragment that contains a complete antigen-recognition and binding site. This fragment consists of a dimer of one heavy-chain and one light-chain variable domain in tight, non-covalent association. Extending from the folding of these two domains are six hypervariable loops (three loops each from the H and L chains), which contribute antigen-binding amino acid residues and confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific HVRs) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

[0061] "Single-chain Fv," also abbreviated as "sFv" or "scFv," is an antibody fragment comprising a VH and VL antibody domain linked into a single polypeptide chain. Preferably, the sFv polypeptide further comprises a V H Domain and V L A polypeptide linker is included between the domains which enables the sFv to form the desired structure for antigen binding.

[0062] Antibody "effector functions" refer to those biological activities attributable to the Fc region of an antibody (a native sequence Fc region or amino acid sequence variant Fc region), and vary with the antibody isotype.

[0063] The term "Fc region" herein is used to define the C-terminal region of an immunoglobulin heavy chain, including native-sequence Fc regions and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain can vary, the human IgG heavy chain Fc region is usually defined to stretch from the amino acid residue at position Cys226 or Pro230 to its carboxyl terminus. The C-terminal lysine of the Fc region (residue 447 (according to the EU numbering system)) can be removed, for example, during antibody production or purification, or by recombinantly engineering the nucleic acid encoding the antibody heavy chain. Thus, an intact antibody composition may include an antibody population in which all K447 residues have been removed, an antibody population in which the K447 residue has not been removed, and an antibody population having a mixture of antibodies containing and not containing the K447 residue. Suitable native-sequence Fc regions for use in the antibodies of the present disclosure include human IgG1, IgG2, IgG3, and IgG4.

[0064] A "native-sequence Fc region" comprises an amino acid sequence identical to that 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.

[0065] A "variant Fc region" comprises an amino acid sequence that differs from that of a native-sequence Fc region by 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 compared to a native-sequence Fc region or the Fc region of a parent polypeptide, e.g., about one to about ten amino acid substitutions, preferably about one to about five amino acid substitutions, in the native-sequence Fc region or the Fc region of a parent polypeptide. A variant Fc region herein preferably has at least 80% homology with a native-sequence Fc region and / or the Fc region of a parent polypeptide, most preferably at least 90% homology thereto, and more preferably at least 95% homology thereto.

[0066] "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. A preferred FcR is a native-sequence human FcR. Furthermore, a preferred FcR is one that binds IgG antibodies (gamma receptors) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses (including allelic variants and alternatively spliced forms of these receptors). FcγRII receptors include FcγRIIA (an "activating receptor") and FcγRIIB (an "inhibiting receptor"), which have similar amino acid sequences but differ primarily in 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. Other FcRs, including those identified in the future, are encompassed by the term "FcR" herein. FcRs can also extend the serum half-life of antibodies.

[0067] As used herein, "percent (%) amino acid sequence identity" and "homology" with respect to a peptide, polypeptide, or antibody sequence refer 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 percent sequence identity (conservative substitutions are not considered part of sequence identity). Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of ways within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms known in the art necessary to achieve maximum alignment over the full length of the sequences being compared.

[0068] The term "competition," when used in the context of antibodies competing for the same or overlapping epitope, refers to competition between the 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). To determine whether an antibody competes with another antibody, numerous types of competitive binding assays can be used, such as solid-phase direct or indirect radioimmunoassays (RIA), solid-phase direct or indirect enzyme immunoassays (EIA), sandwich competition assays (see, e.g., Stahl 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 assay; solid-phase direct label sandwich assay (see, e.g., Harlow and Lane, 1988, Antibodies, A Laboratory Manual, Cold Spring Harbor Press); solid-phase direct label RIA using 1-125 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., al., 1990, Virology 176:546-552); and direct labeling RIA (Moldenhauer et al., 1990, Scand. J. Immunol. 32:77-82) can be used. Typically, such assays involve the use of purified antigen bound to a solid surface, or cells bearing either of these (unlabeled test antibody and labeled reference antibody). Competitive inhibition is measured by determining the amount of label bound to the solid surface or cells in the presence of the test antibody. Typically, the test antibody is present in excess. Antibodies identified by competitive assays (competing antibodies) include antibodies that bind to the same epitope as the reference antibody and antibodies that bind to adjacent epitopes sufficiently close to the epitope bound by the reference antibody so that steric hindrance occurs.Typically, a competing antibody, when present in excess, inhibits (e.g., reduces) specific binding of a reference antibody to a common antigen by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5%, and / or nearly 100%.

[0069] As used herein, an "interaction" between a GPNMB polypeptide and a second polypeptide includes, but is not limited to, protein-protein interactions, physical interactions, chemical interactions, bonds, covalent bonds, and ionic bonds. As used herein, an antibody "inhibits an interaction" between two polypeptides if the antibody disrupts, reduces, or completely eliminates the interaction between the two polypeptides. An antibody of the present disclosure "inhibits an interaction" between two polypeptides if the antibody binds to one of the two polypeptides. In some embodiments, the interaction can be inhibited by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5%, and / or nearly 100%.

[0070] The term "epitope" includes any determinant capable of binding by an antibody. An epitope is the region of an antigen bound by an antibody targeting that antigen, and, if the antigen is a polypeptide, includes specific amino acids that make direct contact with the antibody. In most cases, epitopes reside on polypeptides, but in some cases, they may reside on other types of molecules, such as nucleic acids. Epitopes may include chemically active surface groups of molecules, such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and may have specific three-dimensional structural characteristics and / or specific charge characteristics. In general, antibodies specific for a particular target antigen preferentially recognize epitopes on the target antigen in a complex mixture of polypeptides and / or macromolecules.

[0071] An "isolated" antibody, e.g., an isolated anti-GPNMB antibody of the present disclosure, is one that has been identified, separated, and / or recovered from a component of its production environment (e.g., natural or recombinant). Preferably, an isolated antibody is free of association with all other contaminating components from its production environment. Contaminating components from its production environment, such as those arising from recombinantly transfected cells, are substances that would normally interfere with research, diagnostic, or therapeutic uses of the antibody and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the antibody is purified: (1) to greater than 95% by weight, and in some embodiments, greater than 99% by weight, of the antibody, as determined, for example, by the Lowry method; (2) sufficiently to obtain at least 15 residues of N-terminal or internal amino acid sequence using a spinning cup sequenator; or (3) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver staining. Because at least one component of the antibody's natural environment will be absent, an isolated antibody includes the antibody in situ within recombinant T cells. Ordinarily, however, isolated polypeptide or antibody will be prepared by at least one purification step.

[0072] 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 contaminant nucleic acid molecule with which it is normally associated in the environment in which it is produced. Preferably, an isolated nucleic acid is free from association with all components associated with the production environment. Isolated nucleic acid molecules encoding the polypeptides and antibodies herein are in a form other than that in which they are found in nature. Thus, isolated nucleic acid molecules are distinguished from nucleic acids encoding the polypeptides and antibodies herein that naturally occur in cells.

[0073] As used herein, the term "vector" is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid," which refers to a circular double-stranded DNA into which additional DNA segments can be ligated. Another type of vector is a phage vector. Another kind of vector is a viral vector, into which additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operably linked. Such vectors are referred to herein as "recombinant expression vectors" or simply, "expression vectors." In general, expression vectors useful in recombinant DNA techniques are often in the form of plasmids. As the plasmid is the most commonly used form of vector, "plasmid" and "vector" may be used interchangeably herein.

[0074] "Polynucleotide" or "nucleic acid," used interchangeably herein, refer to a polymer of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or a synthetic reaction.

[0075] A "host cell" includes an individual cell or cell culture that can be or has been the recipient of a vector(s) for incorporating a polynucleotide insert. A host cell includes the progeny of a single host cell, although the progeny may not necessarily be completely identical (in morphology or genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected in vivo with a polynucleotide(s) of the invention.

[0076] As used herein, a "carrier" includes a pharmaceutically acceptable carrier, excipient, or stabilizer that is non-toxic to cells or mammals exposed at the dosages and concentrations employed.

[0077] As used herein, the term "treatment" refers to a clinical intervention designed to alter the natural course of a treated individual's clinical pathology. Desirable effects of treatment include reducing the rate of progression, improving or alleviating the condition, and remission or improving the prognosis of a particular disease, disorder, or condition. For example, an individual is successfully "treated" if one or more symptoms associated with a particular disease, disorder, or condition are alleviated or eliminated.

[0078] An "effective amount" refers to at least an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. An effective amount may be provided in one or more administrations. An effective amount is also an amount in which any toxic or detrimental effects of the treatment are outweighed by the therapeutically beneficial effects. In therapeutic applications, beneficial or desired results include clinical results, such as a reduction in one or more symptoms attributable to the disease, an improvement in the quality of life of those suffering from the disease, a reduction in the dosage of other drugs required to treat the disease, augmentation of other drug therapies, e.g., by targeting, a delay in disease progression, and / or an extension of survival. An effective amount of a drug, compound, or pharmaceutical composition is an amount sufficient to achieve a therapeutic treatment directly or indirectly. As understood in a clinical context, an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, an "effective amount" may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be administered in an effective amount if a desired result can be obtained or achieved in combination with one or more other agents.

[0079] An "individual" for purposes of treatment refers to any animal classified as a mammal, including humans, domestic 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 individual is a human.

[0080] As used herein, administration "in conjunction" or "in combination" with another compound or composition includes simultaneous administration and / or administration at different times. Concurrent or combined administration also includes administration as a co-formulation or as separate compositions (including different dosing frequencies or intervals), and using the same or different routes of administration. In some embodiments, concurrent administration is administration as part of the same treatment regimen.

[0081] The term "about," as used herein, refers to a customary range of error for each value, which is readily understood by one of ordinary skill in the art. Reference herein to "about" a value or parameter includes (and describes) embodiments that are directed to the value or parameter itself.

[0082] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, a reference to an "antibody" is a reference to one to many antibodies, such as molar amounts, and includes equivalents thereof known to those skilled in the art, and so forth.

[0083] It is understood that aspects and embodiments of the present disclosure described herein include "comprising," "consisting of," and "consisting essentially of" aspects and embodiments.

[0084] Anti-GPNMB antibody Monovalent anti-GPNMB antibodies are provided herein. The antibodies provided herein are useful, for example, for treating GPNMB-related disorders.

[0085] In one aspect, the present disclosure provides isolated (e.g., monoclonal) antibodies that bind to an epitope within a GPNMB protein or polypeptide of the present disclosure. GPNMB proteins or polypeptides of the present disclosure include, but are not limited to, mammalian GPNMB proteins or polypeptides, human GPNMB proteins or polypeptides, mouse (murine) GPNMB proteins or polypeptides, and cynomolgus monkey GPNMB proteins or polypeptides. GPNMB proteins and polypeptides of the present disclosure include naturally occurring variants of GPNMB. In some embodiments, the GPNMB proteins and polypeptides of the present disclosure are membrane-bound. In some embodiments, the GPNMB proteins and polypeptides of the present disclosure are the soluble extracellular domain of GPNMB.

[0086] 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, oligokaryocytes, and melanocytes. In addition, GPNMB is ectopic or overexpressed in numerous cancers (Linger et al., 2008, Adv Cancer Res, 100:35-83).

[0087] In some aspects, the anti-GPNMB antibodies of the present disclosure bind to human GPNMB, to mouse GPNMB, to cynomolgus monkey GPNMB, to both human GPNMB and mouse GPNMB, or to human GPNMB, mouse GPNMB, and cynomolgus monkey GPNMB.

[0088] In some embodiments, anti-GPNMB antibodies of the present disclosure bind to human GPNMB with an affinity of about 0.4 nM to about 120 nM. In some embodiments, anti-GPNMB antibodies of the present disclosure bind to mouse GPNMB with an affinity of about 0.3 nM to about 5 nM. In some embodiments, anti-GPNMB antibodies of the present disclosure bind to cynomolgus monkey GPNMB with an affinity of about 0.4 nM to about 1.04 nM. In other embodiments, anti-GPNMB antibodies of the present disclosure bind to human GPNMB with an affinity of about 0.14 nM to about 0.65 nM and to mouse GPNMB with an affinity of about 0.18 nM to about 0.44 nM.

[0089] In some embodiments, the anti-GPNMB antibodies of the present disclosure are antagonistic antibodies. In some embodiments, the anti-GPNMB antibodies of the present disclosure increase the expression level of PDL1 (e.g., in macrophages), increase the expression level of CD40 (e.g., in macrophages), increase the expression level of CD80 (e.g., in macrophages), and increase the serum cytokine expression levels of IL-12p40 and CCL5. In some embodiments, the anti-GPNMB antibodies of the present disclosure promote macrophage activation.

[0090] In some embodiments, the anti-GPNMB antibodies of the present disclosure increase the expression level of GCase (e.g., in macrophages), and are effective in overcoming the decrease in GCase activity associated with reduced progranulin levels.

[0091] In some embodiments, the anti-GPNMB antibodies of the present disclosure reduce GPNMB expression levels in cells (e.g., in macrophages), hi some embodiments, the anti-GPNMB antibodies of the present disclosure reduce LAMP2 expression levels in cells (e.g., in macrophages, monocytes, neutrophils).

[0092] In some embodiments, the anti-GPNMB antibodies of the present disclosure inhibit or reduce inflammasome activation, hi some embodiments, the anti-GPNMB antibodies of the present disclosure inhibit IL-1β expression or release.

[0093] In some aspects, the anti-GPNMB antibodies of the present disclosure reduce neuroinflammation, hi some aspects, the anti-GPNMB antibodies of the present disclosure reduce the expression of C1q, GFAP, IBA1, and CTSD, which are associated with neuroinflammation.

[0094] In some aspects, the anti-GPNMB antibodies of the present disclosure reduce lysosomal stress.

[0095] GPNMB protein Human GPNMB is a type 1 transmembrane glycoprotein that occurs as a result of alternative splicing, resulting in two polypeptide isoforms: one of 572 amino acids and one of 560 amino acids shorter. GPNMB contains 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 (dileusin) motif (Abdelmagid et al., 2008, Exp Cell Res, 314:2334-2351). GPNMB can be cleaved by the metalloproteinase ADAM10, releasing soluble fragments that can bind to various receptors and induce cellular responses (Rose et al., 2010, PLoS One, 5(8):e12093).

[0096] GPNMB, Lysosomal Dysfunction, and Parkinson's Disease Glucocerebrosidase is a lysosomal β-glucosidase that degrades glucosylceramide. Genetic deficiency of glucocerebrosidase is the cause of autosomal recessive Gaucher disease, the most common lysosomal storage disorder (Brady et al., 1966, J Clin Invest, 45:1112-1115). This disease is caused by mutations in the lysosomal hydrolase β-glucosidase glycocerebrosidase, which leads to the accumulation of its substrate, glycosylceramide (van der Lienden et al., 2018, Int Journal of Molecular Sciences, 20:66). Genetic deficiency of glucocerebrosidase is also a risk factor for Parkinson's disease and Ruby body dementia (Sidransky et al., 2009, N Eng J Med, 361:1651-1661; Tsuang et al., 2012, Neurology, 79:1944-1950). Conduritol-β-epoxide (CBE) is an irreversible inhibitor of glucocerebrosidase and is used to generate in vitro and in vivo models for investigating Gaucher disease and Parkinson's disease. Systemic inhibition of lysosomal glucocerebrosidase using conduritol-β-epoxide (CBE) is associated with certain Parkinson's disease-related pathologies, including the accumulation of α-synuclein aggregates, elevated glycosphingolipids, and widespread neuroinflammation (Rocha et al., 2015, Antioxid Redox Signal, 23:550-564).

[0097] Parkinson's disease is a progressive disorder that affects movement and is recognized as the second most common neurodegenerative disorder after Alzheimer's disease. Common symptoms of Parkinson's disease include resting tremor, rigidity, and bradycardia, and non-motor symptoms such as depression, constipation, pain, sleep disturbances, genitourinary disorders, cognitive decline, and olfactory dysfunction are also increasingly associated with the disorder. The main features of Parkinson's disease are

[0098] Recent studies have shown an association between mutations in the glucocerebrosidase gene and an increased risk of Parkinson's disease, with more severe mutations conferring higher levels of risk. Decreased glucocerebrosidase activity has been reported in the substantia nigra, cerebellum, and caudate of Parkinson's disease patients (Alcalay et al., 2015, Brain 138:2648).

[0099] Glucocerebrosidase mutations result in increased toxic activity and / or altered cellular function due to the 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).

[0100] Increased expression of GPNMB in the brain has been detected in a diverse number of 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). Furthermore, the single nucleotide polymorphism (SNP) rs199347, a known top 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).

[0101] The present disclosure shows that reducing GPNMB activity or expression with anti-GNPMB antibodies increases glucocerebrosidase activity.

[0102] GPNMB and Cancer The expression and function of GPNMB have been linked to cancer. GPNMB was first identified as a differentially expressed gene between 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 reported 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 increased invasiveness in vitro and promoted metastasis in vivo (Onaga et al., 2003, J Hepatol, 39:779-785; Rich and Shi, 2003, J Biol Chem, 278:15951-15957).

[0103] GPNMB is highly expressed in multiple tumor types, including triple-negative breast cancer, uveal and cutaneous melanoma, glioblastoma, hepatocellular carcinoma, prostate cancer, osteosarcoma, lung cancer, bladder cancer, and lymphangioleiomyomatosis (Taya and Hammes, 2018, Steroids, 133:102-107). GPNMB has been shown to promote tumor cell migration, invasion, and metastasis. GPNMB's role in promoting tumor progression is through its ability to suppress inflammatory responses surrounding cancer growth (Maric et al., 2013, Onc Targets Therapy, 6:839-852).

[0104] An antibody against GPNMB (called glembatumumab vedotin) was evaluated in Phase I / II clinical trials as a treatment for advanced breast cancer and melanoma, but these trials were halted in 2018 after the drug candidate failed to improve survival or halt tumor progression (Saade et al., 2021, Frontiers in Immunol, 12:674-739). The present disclosure shows that reducing GPNMB activity or expression with anti-GNPMB antibodies reduces tumor growth in mouse tumor models.

[0105] Exemplary Anti-GPNMB Antibodies and Other Specific Antibody Embodiments In some embodiments, (a) an HVR-H1 comprising an amino acid sequence selected from the group consisting 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; (b) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75; (c) HVR-H2 comprising an amino acid sequence selected from the group consisting 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, and 79; (d) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 1 (e) an HVR-L1 comprising an amino acid sequence selected from the group consisting 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, and 156; Provided herein are anti-GPNMB antibodies comprising at least one, two, three, four, five, or six HVRs selected from (f) HVR-L2 and (g) HVR-L3 comprising an amino acid sequence selected from the group consisting 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, and 157.

[0106] In some embodiments, (a) an HVR-H1 comprising an amino acid sequence selected from the group consisting 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; (b) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 64, 65, 66, 67, 68, 71, 74, and 77; (c) an HVR-H2 comprising an amino acid sequence selected from the group consisting 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, and 79; and (d) an HVR-H3 comprising an amino acid sequence selected from the group consisting 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, and 79. H Anti-GPNMB antibodies comprising HVR sequences are provided herein.

[0107] In some aspects, (a) an HVR-L1 comprising an amino acid sequence selected from the group consisting 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, and 155; (b) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 149, 152, and 155; and (c) an HVR-L2 comprising an amino acid sequence selected from the group consisting 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, and 157. L Anti-GPNMB antibodies comprising HVR sequences are provided herein.

[0108] In some aspects, (a) an HVR-H1 comprising (i) an amino acid sequence selected from the group consisting 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 (ii) an HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 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 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, and 79. H V containing HVR sequences H and (b) (i) an HVR-L1 comprising an amino acid sequence selected from the group consisting 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, and 155; and (ii) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 149, 152, and 155. and (iii) an HVR-L2 comprising an amino acid sequence selected from the group consisting 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, and 157. L V containing HVR sequences L and a domain,

[0109] In some aspects, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 7, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 83, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 84, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85. (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 86, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 87, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID 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-L1 comprising the amino acid sequence of SEQ ID NO: 14, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 15, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. (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: 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: 94. (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: 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) SEQ ID NO: 1 (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: 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: 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 (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: 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) sequence HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124, (a) HVR-H1 comprising the amino acid sequence of SEQ ID 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 (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: 58, (d) HVR-L1 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: 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) sequence (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: 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: 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: 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, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 76. (b) HVR-H1 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, as well as (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: 79, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 155,Provided herein is an anti-GPNMB antibody comprising: (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.

[0110] In another aspect, the anti-GPNMB antibody comprises a heavy chain variable domain (V) 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 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 In certain embodiments, a V has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from the group consisting 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 The sequences contain substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but anti-GPNMB antibodies containing the sequences retain the ability to bind to GPNMB. In certain embodiments, a total of 1 to 10 amino acids are substituted, inserted, and / or deleted 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. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., FRs). Optionally, the anti-GPNMB antibody comprises the V 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 In certain embodiments, VH (a) HVR-H1 comprising an amino acid sequence selected from the group consisting 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; (b) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 67, 68, 71, 74, and 77; and (c) HVR-H2 comprising an amino acid sequence selected from the group consisting 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, and 79.

[0111] In another aspect, an anti-GPNMB antibody is provided, the antibody comprising a light chain variable domain (V) 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 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. L In certain embodiments, a V has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from the group consisting 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, and 210. LThe sequences contain substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, but anti-GPNMB antibodies containing the sequences retain the ability to bind to GPNMB. In some embodiments, a total of 1 to 10 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 embodiments, 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 embodiments, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., FRs). Optionally, the anti-GPNMB antibody comprises a V 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 In certain embodiments, V L(a) an HVR-L1 comprising an amino acid sequence selected from the group consisting 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, and 155; (b) an HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 149, 152, and 155; and (c) an HVR-L2 comprising an amino acid sequence selected from the group consisting 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, and 157.

[0112] In some embodiments, an anti-GPNMB antibody is provided, which antibody comprises a V as in any of the embodiments provided above. H and V as in any of the embodiments provided above. L In some embodiments, provided herein are anti-GPNMB antibodies, which comprise a V as in any of the embodiments provided above. H , V as in any of the embodiments provided above L In one embodiment, the antibody comprises the V and 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, 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 The sequence (including post-translational modifications of that sequence) is included.

[0113] In some embodiments, the heavy chain variable domain (V H ) and the light chain variable domain (V L ) and V H and V L 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 H and 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 se...

Claims

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

2. 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 cell surface expression of CD40 on human macrophages.

5. The anti-GPNMB antibody of any one of claims 1 to 4, wherein the anti-GPNMB antibody increases cell surface expression of CD80 on 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 interferon pathway gene expression patterns in human macrophages.

10. 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 mouse 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 serum CCL5 levels.

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 independently 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 cell surface.

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

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

21. 21. The anti-GPNMB antibody of any one of claims 1 to 20, wherein the anti-GPNMB antibody reduces GPNMB expression levels in cells, optionally macrophages.

22. 22. The anti-GPNMB antibody of any one of claims 1 to 21, wherein the anti-GPNMB antibody reduces LAMP2 expression levels in cells, optionally macrophages, monocytes, or neutrophils.

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 the expression or release of IL-1β.

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 binds to GPNMB and is 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-48, GPN-52, and GPN-61.

28. The anti-GPNMB antibody of any one of claims 1 to 27, which competes with one or more antibodies selected from 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.

29. the anti-GPNMB antibody comprises a light chain variable domain and a heavy chain variable domain, and the light chain variable domain, the heavy chain variable domain, or both are 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-48, GPN-52, GPN-61, GPN-65, GPN-81, and GPN-82; 29. The anti-GPNMB antibody of any one of claims 1 to 28, comprising 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-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. 30. The anti-GPNMB antibody of claim 29, the HVR-H1 comprises an amino acid sequence selected from the group consisting 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; b. the HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 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 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; d. the HVR-L1 comprises an amino acid sequence selected from the group consisting 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; e. the HVR-L2 comprises an amino acid sequence selected from the group consisting 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 / or f. The anti-GPNMB antibody of claim 29, wherein the HVR-L3 comprises an amino acid sequence selected from the group consisting 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.

31. 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 l. 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 The anti-GPNMB antibody of claim 29 or 30, wherein 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. 1. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, the anti-GPNMB antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), the heavy chain variable region (VH) comprising: a. 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; b. HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 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. The anti-GPNMB antibody, comprising 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 light chain variable region (VL) a. 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; b. 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. The antibody of claim 32, comprising 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. 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. 35. The antibody of any one of claims 32-34, 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. 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 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.

37. 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 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.

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

97.

41. The antibody a. comprising the HVRs 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. comprising the HVRs 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; or c. comprising the HVRs 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; or d. comprising 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; or e. comprising the HVRs 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; or f. A polypeptide comprising the HVRs 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. A polypeptide comprising the HVRs 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; or h. A polypeptide comprising the HVRs of claim 40.h. and 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. comprising the HVRs 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; or j. A polypeptide comprising the HVRs 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; or k. A polypeptide comprising the HVRs 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. A polypeptide comprising the HVRs 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; or m.

40. A polypeptide comprising the HVRs of claim m. and 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; or n. comprising 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; or o. A polypeptide comprising the HVRs of claim 40.o. and 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; or p.

40. A human HIV comprising the HVRs 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. A polypeptide comprising the HVRs 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; or r. comprising the HVRs 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. Claim 40. s. comprises the HVRs of claim 40. s. and further 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: 197; t. comprising the HVRs 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. Claim 40. u., comprising the HVRs 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. Claim 40. A polypeptide comprising the HVRs of claim 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; or w. Claim 40. A human HIV comprising the HVRs of claim 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. Claim 40. x., comprising the HVRs of claim 40, 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. A polypeptide comprising the HVRs 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; or z. A polypeptide comprising the HVRs 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; or aa.

40. A human HIV comprising the HVRs of claim 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.

40. A polypeptide comprising the HVRs of claim bb. and 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; or cc.

40. A polypeptide comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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 40. A polypeptide comprising an HVR as set forth in 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.

40. A polypeptide comprising the HVRs of claim hh. and 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. A polypeptide comprising the HVR of claim 40.ii. and 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 40. A polypeptide comprising an HVR as set forth in 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; 40.kk. comprising the HVRs 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. A polypeptide comprising the HVRs 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; or mm.

40. A human avian serotype comprising the HVRs of claim 40, 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.

40. A human avian serotype comprising the HVRs of claim 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 40.

00. comprises an HVR according to claim 40.

00. and further 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: 240; p.p.

40. pp. 221-225, 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.

40. The antibody of claim 40, comprising the HVRs of claim 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 a. comprising the HVRs 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. comprising the HVRs 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; or c. comprising the HVRs 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; or d. comprising 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; or e. comprising the HVRs 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. A human HIV comprising 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. A human HIV comprising the HVRs 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. A polypeptide comprising the HVRs of claim 40.h. and 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. comprising the HVRs 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. A polypeptide comprising the HVRs of claim 40.j. and 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. A human HIV comprising 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. A human HIV comprising the HVRs 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; or m.

40. A human HIV comprising the HVR of claim 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. comprising 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. comprising the HVRs 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; or p.

40. A human HIV comprising the HVRs of claim 40, 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. A human HIV comprising 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. comprising 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. Claim 40. s. comprises the HVRs of claim s. and 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: 198; t. Claim 40. t., comprising the HVRs of claim 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. Claim 40. u., comprising the HVRs 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. Claim 40. A human HIV comprising the HVRs of claim 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; or 40. A human HIV comprising the HVRs of claim 40 and 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. Claim 40. x., comprising the HVR of claim 40, 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. Claim 40. y. comprises the HVRs of claim y. and 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: 210; z. A human HIV comprising the HVRs 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.

40. A human HIV comprising the HVRs of claim aa. and 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.

40. A human HIV comprising the HVRs of claim 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.

40. A human virion comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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.

40. A human HIV comprising the HVRs of claim 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 40. A method for the preparation of a human immunodeficiency virus (HVR) comprising: hh.

40. A human avian serotype comprising the HVRs of claim 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. A human virion comprising 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 40. A polypeptide comprising an HVR as set forth in 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; 40.kk. comprising the HVRs 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. A human HIV vector comprising the HVRs of claim 40.

11. and 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.

40. A human HIV vector comprising the HVRs of claim 40, 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.

40. A human HIV comprising the HVRs of claim 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 40.

00. comprises an HVR according to claim 40.

00. and 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: 253; p.p.

40. The HVRs of claim 40, pp. 111-115, 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.

40. The antibody of claim 40 or 41, comprising the HVRs of claim 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 a. comprising the HVRs of claim 40.a. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 161; b. comprising the HVRs of claim 40.b. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 163; or c. comprising the HVR of claim 40.c., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 165; d. A human virion comprising the HVR of claim 40.d., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 167; or e. A human virion comprising the HVR of claim 40.e., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 169; f. A human HIV comprising the HVR of claim 40.f., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 171; g. A human HIV comprising the HVR of claim 40.g., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 173; or h. A human HIV vector comprising the HVR of claim 40.h., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 175; i. comprising the HVRs of claim 40.i., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 177; or j. A human HIV comprising the HVR of claim 40.j., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 179; k. A human virion comprising the HVR of claim 40.k., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 181; or 1. A human virion comprising the HVR of claim 40.

1. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 183; or m. comprising the HVR of claim 40. m., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 185; or n. A human virion comprising the HVR of claim 40.n., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 187; or o. A human virion comprising the HVR of claim 40.o., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 189; or p.

40. A method according to claim 40, comprising the HVRs of claim 40, further comprising a VH comprising the amino acid sequence of SEQ ID NO: 191; q. A human HIV comprising the HVR of claim 40.q., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 193; or r. comprising the HVR of claim 40. r., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 195; s.

40. A method for the preparation of a human immunodeficiency virus (HVR) comprising: t. comprising the HVR of claim 40.t., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 199; u. A human HIV comprising the HVR of claim 40.u., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 201; v. A human HIV vector comprising the HVRs of claim 40. v. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 203; or w. A human HIV vector comprising the HVR of claim 40.w., and further comprising a human HIV vector comprising the amino acid sequence of SEQ ID NO: 205; or x. A human HIV vector comprising the HVR of claim 40.x., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 207; or y. A human HIV vector comprising the HVR of claim 40.y., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 209; or z. A human HIV vector comprising the HVR of claim 40.z., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 234; or aa.

40. A human virion comprising the HVRs of claim aa. and a human VH comprising the amino acid sequence of SEQ ID NO: 235; bb.

40. A human HIV comprising the HVR of claim bb., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; or cc.

40. A human virion comprising the HVR of claim cc., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; dd.

40. A human virion comprising the HVRs of claim dd., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 238; ee.

40. A human HIV comprising the HVRs of claim ee. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 236; ff.

40. A human HIV vector comprising the HVR of claim ff., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; gg 40. A method for the preparation of a human immunodeficiency virus (HVR) comprising: hh.

40. A method according to claim 40, comprising the HVR of claim hh. and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 237; ii. A human HIV vector comprising the HVR of claim 40.ii., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 238; or jj 40. A method for the preparation of a human immunodeficiency virus (HVR) comprising: 40.kk. comprising the HVRs of claim 40.kk., and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 239; or 11. A human HIV-1 antibody comprising the HVRs of claim 40.

11. and a VH comprising the amino acid sequence of SEQ ID NO: 240; mm.

40. A human HIV vector comprising the HVRs of claim 40, further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; or nn.

40. A method according to claim nn., further comprising the steps of: oo 40.

00.

41. A method for the preparation of a human immunodeficiency virus (HVR) comprising: p.p.

40. A human HIV vector comprising the HVRs of claim 40, pp. 111-115, and further comprising a VH comprising the amino acid sequence of SEQ ID NO: 240; or qq. The antibody of any one of claims 40 to 42, comprising the HVRs of claim 40.qq., and further comprising a VH comprising the amino acid sequence of SEQ ID NO:

240.

44. The antibody a. A human virion comprising the HVR of claim 40.a. and a human virion comprising the amino acid sequence of SEQ ID NO: 162; b. A human virion comprising the HVR of claim 40.b., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 164; or c. comprising the HVR of claim 40.c., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; or d. A human virion comprising the HVR of claim 40.d., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 168; or e. A human virion comprising the HVR of claim 40.e., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 170; f. A human virion comprising the HVR of claim 40.f., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 172; or g. A human HIV vector comprising the HVR of claim 40.g., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 174; or h. A human HIV vector comprising the HVR of claim 40.h., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 176; i. comprising the HVR of claim 40.i., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 178; or j. A human virion comprising the HVR of claim 40.j., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 180; k. A human virion comprising the HVR of claim 40.k., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 182; or 1. A human virion comprising the HVR of claim 40.1., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 184; or m. comprising the HVR of claim 40. m., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 186; or n. A human virion comprising the HVR of claim 40.n., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 188; o. A human virion comprising the HVR of claim 40.o., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 190; p.

40. A human HIV vector comprising the HVR of claim 40, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 192; or q. A human virion comprising the HVR of claim 40.q., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 194; or r. comprising the HVR of claim 40. r., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 196; s. comprising the HVR of claim 40.s. and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 198; t. comprising the HVR of claim 40.t., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 200; u. A human virion comprising the HVR of claim 40.u., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 202; or v. A human HIV vector comprising the HVRs of claim 40. v., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 204; or 40. A human virion comprising the HVR of claim 40, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 206; x. A human HIV vector according to claim 40., further comprising a VL comprising the amino acid sequence of SEQ ID NO: 208; y. A human virion comprising the HVR of claim 40.y., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 210; z. A human virion comprising the HVR of claim 40.z., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 241; or aa.

40. A human virion comprising the HVRs of claim aa. and a VL comprising the amino acid sequence of SEQ ID NO: 242; bb.

40. A human virion comprising the HVRs of claim bb., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 243; or cc.

40. A human virion comprising the HVR of claim cc., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 243; dd. A human virion comprising the HVR of claim 40.dd., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 244; ee.

40. A human HIV vector comprising the HVRs of claim ee. and a VL comprising the amino acid sequence of SEQ ID NO: 245; ff.

40. A human HIV vector comprising the HVR of claim ff., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 245; gg 40. A method for the preparation of a human immunodeficiency virus (HVR) comprising: hh.

40. A human virion comprising the HVR of claim hh., and a human virion comprising the amino acid sequence of SEQ ID NO: 247; or ii. A human virion comprising the HVR of claim 40.ii., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 247; or jj 40. A method for the treatment of a leukemia comprising administering to a patient a vaccine comprising the HVR of claim 40.jj and a VL comprising the amino acid sequence of SEQ ID NO: 248; 40.kk. comprising the HVRs of claim 40.kk., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 249; 11. A human HIV vector comprising the HVRs of claim 40.

11. and a VL comprising the amino acid sequence of SEQ ID NO: 250; or mm.

40. A human HIV vector comprising the HVR of claim 40, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 251; nn.

40. A human virion comprising the HVRs of claim nn., and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 252; oo 40.

00. A human virion comprising the HVRs of claim 40.

00. and a human virion comprising the amino acid sequence of SEQ ID NO: 253; or p.p.

40. A human virion comprising the HVRs of claim 40, pp. 111-115, and further comprising a VL comprising the amino acid sequence of SEQ ID NO: 254; or qq. The antibody of any one of claims 40 to 43, comprising the HVRs of claim 40.qq. and further comprising a VL comprising the amino acid sequence of SEQ ID NO:

249.

45. The antibody 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); l. 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. 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); 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. 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); 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. VH comprising the amino acid sequence of SEQ ID NO: 238, and VL comprising the amino acid sequence of SEQ ID NO: 244 (as shown in Table 15); ee. 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); ff. VH comprising the amino acid sequence of SEQ ID NO: 237, and VL comprising the amino acid sequence of SEQ ID NO: 245 (as shown in Table 15); 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. 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); 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); ll. 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); 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. The antibody of claim 40, comprising 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).

46. The antibody a. comprising the HVRs 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. comprising the HVRs 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; or c. comprising the HVRs 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; or d. comprising the HVRs 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; or e. comprising the HVRs 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; or f. A antibody comprising the HVRs 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. A antibody comprising the HVRs 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. A antibody comprising the HVRs 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. comprising the HVRs 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; or j. Claim 40. A antibody comprising the HVRs of claim 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. Claim 40. comprising the HVRs of claim 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; l. comprising the HVRs 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; or m. comprising the HVRs 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; or n. comprising the HVRs 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; or o. comprising the HVRs 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; or p.

40. comprising the HVRs 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. A antibody comprising the HVRs 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; or r. Claim 40. z., 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. Claim 40. aa., 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. Claim 40. aa., 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. Claim 40. aa., 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. Claim 40. aa., 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. Claim 40. aa., 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. A heavy chain comprising the HVRs of claim 40. aa., and which 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; or y. Claim 40. aa., 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. A human immunodeficiency virus (HIV) antibody comprising the HVRs 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; or aa.

40. A human immunodeficiency virus (HIV) antibody comprising the HVRs 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. Claim 40. aa., 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., comprising the HVRs 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. Claim 40. aa., 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. Claim 40. aa., 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. Claim 40. aa., 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 40. A human immunodeficiency virus (HIV) antibody comprising the HVRs set forth in claim 40aa. 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; or hh. Claim 40. aa., 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. A heavy chain comprising the HVRs of claim 40. aa., and which 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; or jj 40. A human immunodeficiency virus (HIV) antibody comprising the HVRs set forth in claim 40aa. 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; or or comprising the HVRs of claim 40.kk, 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; ll. comprising the HVRs 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; or or comprising the HVRs of claim 40.mm., 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., 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; or oo., comprising the HVRs 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; or pp., 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; or qq. comprising the HVRs 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; or or comprising the HVRs of claim 40.rr., 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., comprising the HVRs 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; or or comprising the HVRs of claim 40.tt., 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, 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; or vv. comprising the HVRs 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; or or comprising the HVRs of claim 40.ww., 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. comprising the HVRs 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; or yy., comprising the HVRs 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; or zz., comprising the HVRs 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; or aaa., 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; or bbb., comprising the HVRs 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; or ccc., 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; or ddd., 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; or eee., 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; or 40.fff., 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; or comprising the HVRs 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., comprising the HVRs 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. comprising the HVRs 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; or jjj. comprising the HVRs 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., comprising the HVRs 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; or lll. comprising the HVRs 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; or mmm., 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; or nnn., 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; or ooo., comprising the HVRs 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., 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; or qqq. comprising the HVRs 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; or comprising the HVRs 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., comprising the HVRs 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; or ttt., 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; uu u. comprising the HVRs 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; or vvv. comprising the HVRs 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. 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; or xxxx or comprising the HVRs 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. comprising the HVRs 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. comprising the HVRs 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. comprising the HVRs 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., comprising the HVRs 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., comprising the HVRs 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. comprising the HVRs 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., comprising the HVRs 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., comprising the HVRs 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; ggg g. comprising the HVRs 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., comprising the HVRs 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; iii or comprising the HVRs 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 or comprising the HVRs 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. comprising the HVRs 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; lllll. comprising the HVRs 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; or mmmm., comprising the HVRs 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.

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.

40. A method for the preparation of a human immunodeficiency virus (HIV) comprising administering to a mammalian subject the invention, comprising administering to a mammalian subject the invention, comprising administering to a mammalian subject the invention, a method for the preparation of a human immunodeficiency virus (HIV) comprising administering to a mammalian subject the invention, a method for the preparation of a human immunodeficiency virus (HIV) comprising administering to a mammalian subject the invention, ppp p. comprising the HVRs 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.

40. A polypeptide comprising the HVRs 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.

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. comprising the HVRs 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 40. The HVRs of claim 40.kk., 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; uu uu. comprising the HVRs 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. comprising the HVRs 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; www. 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; or xxxx 40. The HVRs of claim 40.kk., 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.

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. Claim 40. kk., 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.

40. comprising the HVRs 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; bbbbbb.

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; cccccc. Claim 40.kk., 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; dddddd.

40. The HVRs of claim 40.kk., 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.

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; or ffffff., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 398; or ggggg or comprising the HVRs 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., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 400; or iiiiii or comprising the HVRs 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 or comprising the HVRs 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; or comprising the HVRs 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 403; 40.lll, 40.mm, 40.nn, 40.oo, 40.pp, or 40.qq, and further comprising a heavy 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; or mmmmm., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 405; or nnnnnn., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 406; or 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; pppppp., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 408; or qqqqq. comprising the HVRs 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 409; or rrrrrr. 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 410; or sssss. comprising the HVRs 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 411; or tttttt or comprising the HVRs 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 412; uuuu uu., 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 at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 413; or vvvvv., comprising the HVRs 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 40. The antibody of claim 40, comprising the HVRs 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 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 a. comprising the HVRs 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. comprising the HVRs 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; or c. comprising the HVRs 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; or d. comprising the HVRs 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; or e. comprising the HVRs 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; or f. comprising the HVRs 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; or g. A human immunodeficiency virus (HVR) comprising the HVRs 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; or h. A human immunodeficiency virus (HIV) antibody comprising the HVRs 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; or i. comprising the HVRs 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; or j. A human immunodeficiency virus (HVR) comprising the HVRs 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; or k. comprising the HVRs 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; or 1. comprising the HVRs 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; or m. comprising the HVRs 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. Claim 40. comprising the HVRs of 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. comprising the HVRs 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; or p 40.

00. comprises the HVRs of claim 40.

00. and further 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: 431; q. comprising the HVRs of claim 40, pp. 111-115, 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 antibody of claim 40 or claim 46, comprising the HVRs 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 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; l. a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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 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; 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; ll. a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; 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: 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; 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: 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; a heavy chain that 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; a heavy chain that 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; 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: 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: 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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: 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: 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 423; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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: 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; 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: 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: 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: 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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: 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; eeeeeeeeeeeee. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; ppppppppppppp. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; zzzzzzzzzzzzz. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 431; eeeeeeeeeeeeeee. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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: 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: 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: 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; ppppppppppppppp. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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: 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: 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; zzzzzzzzzzzzz. A heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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; a heavy chain that 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, or 41. The antibody of claim 40, 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, and a light chain that 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. 1. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, said anti-GPNMB antibody comprising: 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 or 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 or 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; l. 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; 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; 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; 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; a heavy chain comprising the amino acid sequence of SEQ ID NO: 342 or 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; 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; 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; 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; ll. 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; 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; 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; 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; 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; A heavy chain comprising the amino acid sequence of SEQ ID NO: 352 or 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; 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; 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; a heavy chain comprising the amino acid sequence of SEQ ID NO: 340 or 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: 423; 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 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; 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; 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; 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; 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; iii. 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; 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; 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; 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: 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 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; www. 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; 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; dddddd. 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; eeeeeee. 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; 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; iii. 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; 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; 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; pppppp. 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: 415, and a light chain comprising the amino acid sequence of SEQ ID NO: 429; www. 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; xxxxxx. 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; 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: 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; ddddddd. 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; eeeeeee. 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; 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; 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; 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; ppppppp. 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: 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; 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; 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; zzzzzzz. 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; 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; cccccccc. 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; eeeeeeeee. 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 ffffffff. The anti-GPNMB antibody, comprising 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. 1. An isolated anti-glycoprotein non-metastatic melanoma protein B (GPNMB) antibody, wherein the anti-GPNMB antibody is selected from the group consisting of 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-62, GPN-63, GPN-64, GPN-65, GPN-66, GPN-67, GPN-68, GPN-69, GPN-70, GPN-71, GPN-72, GPN-73, GPN-74, GPN-75, GPN-76, GPN-77, GPN-78, GPN-79, GPN-80, 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, GPN-99, GPN-100, GPN-101, GPN-102, GPN-103, GPN-104, GPN-105, GPN-106, GPN-107, GPN-108, GPN-109, GPN-110, GPN-111, GPN-112, GPN-11 The anti-GPNMB antibody comprises a VH comprising HVR-H1, HVR-H2, and HVR-H3, and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of any one of 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 antibodies include 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, GP 51. The isolated antibody of claim 50, comprising a VH and / or VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to that of any one of 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 antibody is selected from the group consisting of 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 52. The isolated antibody of claim 50 or claim 51, comprising the VH and / or VL of any one of 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.

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

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

55. The antibody has the following characteristics: a. the antibody modulates the expression of an activation surface marker on myeloid cells; b. the antibody increases cell surface expression of PD-L1 on human macrophages; c. the antibody increases cell surface expression of CD40 on human macrophages; d. the antibody increases cell surface expression of CD80 on 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 alters interferon pathway gene expression patterns in human macrophages. i. the antibody reduces tumor volume in a mouse tumor model, such as the MC38 tumor model; j. The antibody reduces tumor growth rate in a mouse model, such as the MC38 tumor model. k. the antibody increases the level of IL-12p40 in serum; l. 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 independent 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 decrease in glucocerebrosidase activity associated with reduced progranulin levels; t. the antibody reduces GPNMB expression levels in cells, optionally macrophages; u. the antibody reduces LAMP2 expression levels in cells, optionally macrophages, monocytes, or neutrophils; v. the antibody inhibits or reduces inflammasome activation; w. the antibody inhibits the expression or release of IL-1β; x. the antibody reduces neuroinflammation; y. the antibody reduces the expression of C1q, GFAP, IBA1, and CTSD associated with neuroinflammation; and Z. The antibody of any one of claims 32 to 54, wherein the antibody reduces lysosomal stress.

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

57. 57. The antibody of any one of claims 1 to 56, wherein 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 murine GPNMB with an affinity of about 0.18 nM to about 0.44 nM.

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. 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. 63. The antibody of claim 62, wherein the antibody is of the IgG class and is of the human IgG1, IgG2, IgG3, or IgG4 isotype, or of the murine IgG1 or IgG2 isotype.

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

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

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

67. The antibody has a human or mouse IgG1 isotype and is 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, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q, A32 7G, 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 said residues is according to EU numbering.

68. 68. The antibody of any one of claims 1-45 or 50-67, wherein the antibody has a human or murine 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. 69. The antibody of any one of claims 1-45 or 50-68, wherein the antibody has a human or murine 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. 70. The antibody of any one of claims 1-45 or 50-69, 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 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 Fc amino acid sequence in the IgG is selected from the group consisting of SEQ ID NOs: 213 to 233.

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

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

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

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

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

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

78. 100. A method of treating cancer in a subject in need thereof, 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. 79. The method of claim 78, further comprising administering one or more therapeutic agents.

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

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

82. 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. 83. The method of any one of claims 78 to 82, wherein the cancer is 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. 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. 100. A method of treating a neurodegenerative 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 of any one of claims 1 to 71, thereby treating the disease or disorder.

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

87. 72. A method 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 of any one of claims 1-71, thereby treating the disease or disorder.

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

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

90. 90. The method of claim 89, further comprising quantification of antigen-binding anti-GPNMB antibodies.

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