US2023365699A1PendingUtilityA1
Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
Est. expiryNov 1, 2037(~11.3 yrs left)· nominal 20-yr term from priority
Inventors:Blythe SatherSteven M. ShamahYan ChenRebecca WuCollin HauskinsCsaba PazmanyJui Dutta-SimmonsKimberly Harrington
C07K 16/2875A61P 35/00C07K 14/535C07K 14/70517C07K 14/70521C12N 15/867C07K 2317/52C07K 2317/565C07K 2317/622A61P 37/06C07K 16/2878A61K 2039/505C07K 2317/24C07K 2317/56
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Claims
Abstract
Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (V H ) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A method of treatment, the method comprising administering to a subject having a disease or disorder associated with BCMA an engineered cell comprising a chimeric antigen receptor (CAR) comprising an extracellular domain comprising an anti-BCMA antibody or antigen-binding fragment, a transmembrane domain, and an intracellular signaling region comprising an intracellular signaling domain, wherein the anti-BCMA antibody or antigen-binding fragment comprises a heavy chain variable (V H ) region and a light chain variable (V L ) region, wherein:
the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:116; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:111, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:117; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:118; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:119; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:120; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:121; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:122; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:123; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:112, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:124; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:113, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:125; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:114, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:126; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:127; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:247, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:257; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:248, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:258; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:249, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:259; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:250, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:260; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:251, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:261; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:252, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:262; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:253, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:263; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:254, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:264; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:255, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:265; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:266; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:267; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:518, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:534; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:535; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:536; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:520, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:264; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:521, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:537; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:522, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:538; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:523, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:539; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:540; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:524, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:541; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:525, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:261; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:526, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:542; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:527, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:543; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:528, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:544; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:529, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:545; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:528, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:546; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:522, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:547; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:548; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:530, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:549; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:531, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:550; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:552; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:553; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:118; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:533, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:554; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:555; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:524, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:556; or the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:557, respectively.
2 . The method of claim 1 , wherein:
the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:26, 37, and 47, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 8, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:27, 38, and 48, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:28, 39, and 49, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:29, 40, and 50, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 39, and 51, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:31, 41, and 52, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:32, 42, and 53, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 39, and 54, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 55, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:34, 44, and 56, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 11, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:35, 45, and 57, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:36, 46, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:140, 145, and 149, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 184, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:141, 145, and 149, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 185, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:141, 145, and 150, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 186, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:142, 146, and 151, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 187, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 152, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:175, 180, and 188, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:143, 147, and 153, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 189, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:144, 148, and 154, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:176, 181, and 190, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 155, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:177, 182, and 191, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 156, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 192, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:178, 183, and 193, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:178, 183, and 194, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 399, and 415, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:380, 400, and 416, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 421, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 155, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:177, 182, and 191, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 372, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:381, 401, and 417, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:382, 402, and 418, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 377, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:383, 403, and 419, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:384, 39, and 54, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:385, 180, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 373, and 152, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:175, 180, and 188, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 11, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:386, 404, and 420, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 378, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 421, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:387, 405, and 422, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:388, 406, and 423, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:388, 407, and 424, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:389, 408, and 425, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:390, 183, and 193, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 374, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:391, 409, and 426, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:392, 40, and 427, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:394, 39, and 429, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:395, 411, and 430, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:28, 39, and 49, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:396, 412, and 431, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:396, 412, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:397, 413, and 432, respectively; or the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:398, 414, and 433, respectively.
3 . The method of claim 1 , wherein:
the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 116, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:111 and 117, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 118, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 119, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 120, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 121, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 122, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 123, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:112 and 124, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:113 and 125, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:114 and 126, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 127, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:247 and 257, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:248 and 258, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:249 and 259, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:250 and 260, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:251 and 261, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:252 and 262, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:253 and 263, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:254 and 264, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:255 and 265, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 266, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 267, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:518 and 534, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 535, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 536, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:520 and 264, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:521 and 537, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:522 and 538, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:523 and 539, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 540, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:524 and 541, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:525 and 261, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:526 and 542, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:527 and 543, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:528 and 544, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:529 and 545, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:528 and 546, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:522 and 547, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 548, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:530 and 549, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:531 and 550, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 552, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 553, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 118, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:533 and 554, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 555, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:524 and 556, respectively; or the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 557, respectively.
4 . The method of claim 1 , wherein:
the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 116, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:111 and 117, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 118, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 119, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 120, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 121, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 122, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 123, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:112 and 124, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:113 and 125, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:114 and 126, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 127, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:247 and 257, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:248 and 258, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:249 and 259, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:250 and 260, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:251 and 261, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:252 and 262, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:253 and 263, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:254 and 264, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:255 and 265, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 266, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 267, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:518 and 534, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 535, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 536, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:520 and 264, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:521 and 537, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:522 and 538, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:523 and 539, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 540, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:524 and 541, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:525 and 261, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:526 and 542, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:527 and 543, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:528 and 544, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:529 and 545, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:528 and 546, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:522 and 547, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 548, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:530 and 549, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:531 and 550, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 552, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 553, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 118, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:533 and 554, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 555, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:524 and 556, respectively; or the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 557, respectively.
5 . The method of claim 1 , wherein the anti-BCMA antibody or antigen-binding fragment thereof is an scFv.
6 . The method of claim 5 , wherein the V H region is amino-terminal to the V L region or the V H region is carboxy-terminal to the V L region.
7 . The method of claim 5 , wherein the scFv comprises an amino acid sequence selected from any one of SEQ ID NOS:128-139, 268-278, 558-576 and 578-583, or an amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOS:128-139, 268-278, 558-576 and 578-583.
8 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is human.
9 . The method of claim 1 , wherein the intracellular signaling domain comprises a primary signaling domain, a signaling domain that is capable of inducing a primary activation signal in a T cell, a signaling domain of a T cell receptor (TCR) component, and/or a signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM).
10 . The method of claim 1 , wherein the intracellular signaling domain comprises an intracellular signaling domain of a CD3-zeta (CD3) chain.
11 . The method of claim 1 , wherein the intracellular signaling region further comprises a costimulatory signaling domain.
12 . The method of claim 11 , wherein the costimulatory signaling domain comprises an intracellular signaling domain of a CD28, a 4-1BB or an ICOS.
13 . The method of claim 1 , wherein the disease or disorder is a cancer.
14 . The method of claim 1 , wherein the disease or disorder is multiple myeloma.
15 . A method of treatment, the method comprising administering to a subject having a disease or disorder associated with BCMA an anti-BCMA antibody or antigen-binding fragment, wherein the anti-BCMA antibody or antigen-binding fragment comprises a heavy chain variable (V H ) region and a light chain variable (V L ) region, wherein:
the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:116; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:111, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:117; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:118; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:119; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:120; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:121; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:122; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:123; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:112, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:124; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:113, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:125; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:114, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:126; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:127; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:247, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:257; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:248, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:258; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:249, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:259; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:250, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:260; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:251, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:261; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:252, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:262; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:253, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:263; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:254, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:264; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:255, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:265; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:266; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:267; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:518, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:534; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:535; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:536; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:520, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:264; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:521, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:537; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:522, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:538; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:523, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:539; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:540; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:524, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:541; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:525, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:261; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:526, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:542; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:527, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:543; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:528, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:544; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:529, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:545; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:528, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:546; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:522, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:547; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:256, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:548; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:530, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:549; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:531, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:550; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:552; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:553; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:110, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:118; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:533, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:554; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:115, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:555; the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:524, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:556; or the V H region comprises a CDR-H1, CDR-H2 and CDR-H3 contained within the V H region amino acid sequence of SEQ ID NO:519, and the V L region comprises a CDR-L1, CDR-L2 and CDR-L3 contained within the V L region amino acid sequence of SEQ ID NO:557, respectively.
16 . The method of claim 15 , wherein:
the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:26, 37, and 47, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 8, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:27, 38, and 48, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:28, 39, and 49, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:29, 40, and 50, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 39, and 51, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:31, 41, and 52, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:32, 42, and 53, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 39, and 54, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 55, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:34, 44, and 56, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 11, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:35, 45, and 57, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:36, 46, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:140, 145, and 149, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 184, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:141, 145, and 149, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 185, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:141, 145, and 150, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 186, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:142, 146, and 151, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 187, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 152, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:175, 180, and 188, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:143, 147, and 153, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 189, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:144, 148, and 154, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:176, 181, and 190, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 155, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:177, 182, and 191, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 156, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:174, 179, and 192, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:178, 183, and 193, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:178, 183, and 194, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:30, 399, and 415, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:380, 400, and 416, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 421, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 155, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:177, 182, and 191, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 372, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:381, 401, and 417, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:382, 402, and 418, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 377, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:383, 403, and 419, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:384, 39, and 54, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:385, 180, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 373, and 152, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:175, 180, and 188, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 11, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:386, 404, and 420, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 378, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:33, 43, and 421, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:387, 405, and 422, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:388, 406, and 423, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:388, 407, and 424, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:3, 6, and 376, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:389, 408, and 425, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 157, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:390, 183, and 193, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 374, and 9, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:391, 409, and 426, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:392, 40, and 427, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:394, 39, and 429, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:395, 411, and 430, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:28, 39, and 49, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:396, 412, and 431, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:396, 412, and 58, respectively; the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:2, 5, and 10, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:397, 413, and 432, respectively; or the V H region comprises a CDR-H1, CDR-H2, and CDR-H3 comprising the amino acid sequence of SEQ ID NOS:1, 4, and 7, respectively, and the V L region comprises a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequence of SEQ ID NOS:398, 414, and 433, respectively.
17 . The method of claim 15 , wherein:
the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 116, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:111 and 117, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 118, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 119, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 120, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 121, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 122, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 123, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:112 and 124, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:113 and 125, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:114 and 126, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 127, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:247 and 257, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:248 and 258, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:249 and 259, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:250 and 260, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:251 and 261, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:252 and 262, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:253 and 263, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:254 and 264, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:255 and 265, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 266, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 267, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:518 and 534, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 535, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 536, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:520 and 264, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:521 and 537, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:522 and 538, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:523 and 539, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 540, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:524 and 541, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:525 and 261, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:526 and 542, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:527 and 543, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:528 and 544, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:529 and 545, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:528 and 546, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:522 and 547, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:256 and 548, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:530 and 549, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:531 and 550, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 552, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 553, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:110 and 118, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:533 and 554, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:115 and 555, respectively; the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:524 and 556, respectively; or the V H region and the V L region comprise amino acid sequences having at least 90% sequence identity to SEQ ID NOS:519 and 557, respectively.
18 . The method of claim 15 , wherein:
the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 116, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:111 and 117, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 118, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 119, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 120, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 121, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 122, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 123, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:112 and 124, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:113 and 125, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:114 and 126, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 127, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:247 and 257, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:248 and 258, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:249 and 259, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:250 and 260, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:251 and 261, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:252 and 262, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:253 and 263, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:254 and 264, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:255 and 265, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 266, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 267, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:518 and 534, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 535, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 536, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:520 and 264, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:521 and 537, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:522 and 538, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:523 and 539, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 540, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:524 and 541, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:525 and 261, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:526 and 542, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:527 and 543, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:528 and 544, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:529 and 545, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:528 and 546, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:522 and 547, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:256 and 548, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:530 and 549, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:531 and 550, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 552, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 553, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:110 and 118, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:533 and 554, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:115 and 555, respectively; the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:524 and 556, respectively; or the V H and V L regions comprise the amino acid sequences set forth in SEQ ID NOS:519 and 557, respectively.
19 . The method of claim 15 , wherein the disease or disorder is a cancer.
20 . The method of claim 15 , wherein the disease or disorder is multiple myeloma.Join the waitlist — get patent alerts
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