IP Library › Patent Application 19000442

Patent Application

App. No. 19/000,442

ANTI-TISSUE FACTOR ANTIBODIES, ANTIBODY-DRUG CONJUGATES, AND RELATED METHODS

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Patent No.: US None
App. No.: 19/000,442

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Abstract

Provided herein are antibodies that specifically bind to human tissue factor (TF), anti-TF antibody-drug conjugates (ADCs), and compositions comprising the antibodies or ADCs. Also provided herein are methods of making and using the antibodies or ADCs, such as therapeutic and diagnostic methods.

Claims (171)

1 - 503 . (canceled)

504 . An antibody which binds to the extracellular domain of human Tissue Factor (TF), wherein the antibody comprises

(1) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 37, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 38;

(2) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 75, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 76;

(3) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 113, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 114;

(4) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 189, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 190;

(5) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 227, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 228;

(6) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 265, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 266;

(7) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 303, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 304;

(8) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 341, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 342;

(9) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 379, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 380;

(10) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 417, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 418;

(11) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 455, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 456;

(12) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 493, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 494;

(13) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 531, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 532;

(14) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 569, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 570;

(15) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 607, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 608;

(16) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 645, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 646;

(17) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 683, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 684;

(18) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 721, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 722; or

(19) a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 759, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 760.

505 . The antibody of claim 504 , wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 are determined according to Kabat numbering scheme, Chothia numbering scheme, AbM numbering scheme, Contact numbering scheme, IMGT numbering scheme, or a combination thereof.

506 . The antibody of claim 504 , wherein

(1) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 2, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 3, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 6;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 9, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 10, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 11, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 12;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 13, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 14, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 15, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 16, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 18;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 19, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 20, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 21, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 22, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 23, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 24;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 25, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 26, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 27, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 28, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 29, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 30; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 31, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 32, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 33, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 34, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 36;

(2) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 39, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 40, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 41, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 42, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 43, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 44;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 45, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 46, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 47, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 48, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 49, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 50;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 51, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 52, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 53, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 54, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 56;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 57, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 58, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 59, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 60, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 61, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 62;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 63, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 64, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 65, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 66, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 67, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 68; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 69, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 70, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 71, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 72, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 74;

(3) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 77, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 78, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 79, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 80, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 81, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 82;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 83, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 84, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 85, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 86, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 87, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 88;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 89, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 90, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 91, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 92, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 94;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 95, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 96, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 97, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 98, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 99, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 100;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 101, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 102, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 103, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 104, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 105, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 106; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 107, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 108, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 109, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 110, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 112;

(4) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 153, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 154, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 155, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 156, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 157, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 158;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 159, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 160, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 161, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 162, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 163, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 164;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 165, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 166, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 167, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 168, the VL-CDR2 comprises the amino acid sequence of KAY, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 170;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 171, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 172, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 173, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 174, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 175, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 176;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 177, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 178, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 179, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 180, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 181, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 182; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 183, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 184, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 185, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 186, the VL-CDR2 comprises the amino acid sequence of KAY, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 188;

(5) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 191, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 192, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 193, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 194, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 195, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 196;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 197, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 198, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 199, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 200, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 201, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 202;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 203, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 204, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 205, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 206, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 208;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 209, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 210, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 211, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 212, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 213, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 214;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 215, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 216, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 217, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 218, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 219, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 220; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 221, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 222, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 223, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 224, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 226;

(6) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 229, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 230, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 231, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 232, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 233, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 234;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 235, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 236, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 237, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 238, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 239, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 240;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 241, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 242, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 243, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 244, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 246;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 247, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 248, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 249, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 250, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 251, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 252;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 253, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 254, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 255, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 256, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 257, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 258; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 259, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 260, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 261, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 262, the VL-CDR2 comprises the amino acid sequence of KAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 264;

(7) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 267, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 268, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 269, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 270, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 271, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 272;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 273, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 274, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 275, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 276, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 277, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 278;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 279, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 280, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 281, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 282, the VL-CDR2 comprises the amino acid sequence of SAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 284;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 285, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 286, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 287, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 288, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 289, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 290;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 291, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 292, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 293, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 294, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 295, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 296; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 297, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 298, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 299, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 300, the VL-CDR2 comprises the amino acid sequence of SAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 302;

(8) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 305, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 306, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 307, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 308, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 309, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 310;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 311, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 312, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 313, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 314, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 315, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 316;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 317, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 318, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 319, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 320, the VL-CDR2 comprises the amino acid sequence of WAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 322;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 323, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 324, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 325, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 326, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 327, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 328;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 329, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 330, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 331, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 332, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 333, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 334; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 335, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 336, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 337, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 338, the VL-CDR2 comprises the amino acid sequence of WAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 340;

(9) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 343, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 344, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 345, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 346, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 347, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 348;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 349, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 350, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 351, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 352, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 353, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 354;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 355, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 356, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 357, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 358, the VL-CDR2 comprises the amino acid sequence of WAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 360;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 361, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 362, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 363, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 364, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 365, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 366;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 367, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 368, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 369, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 370, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 371, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 372; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 373, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 374, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 375, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 376, the VL-CDR2 comprises the amino acid sequence of WAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 378;

(10) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 381, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 382, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 383, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 384, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 385, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 386;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 387, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 388, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 389, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 390, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 391, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 392;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 393, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 394, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 395, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 396, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 398;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 399, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 400, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 401, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 402, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 403, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 404;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 405, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 406, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 407, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 408, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 409, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 410; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 411, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 412, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 413, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 414, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 416;

(11) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 419, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 420, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 421, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 422, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 423, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 424;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 425, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 426, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 427, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 428, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 429, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 430;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 431, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 432, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 433, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 434, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 436;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 437, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 438, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 439, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 440, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 441, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 442;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 443, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 444, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 445, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 446, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 447, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 448; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 449, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 450, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 451, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 452, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 454;

(12) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 457, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 458, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 459, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 460, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 461, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 462;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 463, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 464, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 465, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 466, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 467, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 468;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 469, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 470, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 471, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 472, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 474;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 475, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 476, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 477, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 478, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 479, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 480;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 481, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 482, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 483, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 484, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 485, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 486; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 487, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 488, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 489, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 490, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 492;

(13) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 495, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 496, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 497, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 498, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 499, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 500;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 501, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 502, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 503, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 504, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 505, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 506;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 507, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 508, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 509, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 510, the VL-CDR2 comprises the amino acid sequence of GAD, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 512;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 513, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 514, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 515, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 516, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 517, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 518;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 519, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 520, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 521, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 522, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 523, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 524; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 525, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 526, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 527, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 528, the VL-CDR2 comprises the amino acid sequence of GAD, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 530;

(14) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 533, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 534, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 535, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 536, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 537, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 538;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 539, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 540, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 541, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 542, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 543, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 544;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 545, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 546, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 547, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 548, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 550;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 551, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 552, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 553, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 554, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 555, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 556;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 557, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 558, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 559, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 560, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 561, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 562; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 563, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 564, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 565, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 566, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 568;

(15) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 571, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 572, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 573, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 574, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 575, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 576;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 577, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 578, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 579, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 580, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 581, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 582;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 583, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 584, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 585, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 586, the VL-CDR2 comprises the amino acid sequence of GAF, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 588;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 589, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 590, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 591, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 592, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 593, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 594;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 595, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 596, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 597, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 598, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 599, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 600; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 601, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 602, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 603, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 604, the VL-CDR2 comprises the amino acid sequence of GAF, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 606;

(16) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 609, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 610, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 611, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 612, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 613, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 614;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 615, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 616, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 617, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 618, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 619, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 620;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 621, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 622, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 623, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 624, the VL-CDR2 comprises the amino acid sequence of GAY, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 626;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 627, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 628, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 629, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 630, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 631, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 632;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 633, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 634, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 635, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 636, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 637, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 638; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 639, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 640, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 641, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 642, the VL-CDR2 comprises the amino acid sequence of GAY, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 644;

(17) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 647, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 648, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 649, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 650, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 651, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 652;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 653, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 654, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 655, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 656, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 657, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 658;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 659, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 660, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 661, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 662, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 664;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 665, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 666, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 667, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 668, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 669, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 670;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 671, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 672, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 673, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 674, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 675, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 676; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 677, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 678, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 679, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 680, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 682;

(18) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 685, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 686, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 687, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 688, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 689, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 690;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 691, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 692, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 693, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 694, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 695, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 696;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 697, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 698, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 699, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 700, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 702;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 703, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 704, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 705, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 706, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 707, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 708;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 709, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 710, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 711, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 712, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 713, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 714; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 715, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 716, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 717, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 718, the VL-CDR2 comprises the amino acid sequence of GAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 720; or

(19) (i) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 723, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 724, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 725, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 726, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 727, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 728;

(ii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 729, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 730, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 731, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 732, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 733, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 734;

(iii) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 735, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 736, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 737, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 738, the VL-CDR2 comprises the amino acid sequence of DAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 740;

(iv) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 741, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 742, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 743, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 744, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 745, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 746;

(v) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 747, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 748, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 749, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 750, the VL-CDR2 comprises the amino acid sequence of SEQ ID NO: 751, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 752; or

(vi) the VH-CDR1 comprises the amino acid sequence of SEQ ID NO: 753, the VH-CDR2 comprises the amino acid sequence of SEQ ID NO: 754, the VH-CDR3 comprises the amino acid sequence of SEQ ID NO: 755, the VL-CDR1 comprises the amino acid sequence of SEQ ID NO: 756, the VL-CDR2 comprises the amino acid sequence of DAS, and the VL-CDR3 comprises the amino acid sequence of SEQ ID NO: 758.

507 . The antibody of claim 504 , wherein the antibody comprises:

(1) a VH sequence of SEQ ID NO: 37 and a VL sequence of SEQ ID NO: 38;

(2) a VH sequence of SEQ ID NO: 75 and a VL sequence of SEQ ID NO: 76;

(3) a VH sequence of SEQ ID NO: 113 and a VL sequence of SEQ ID NO: 114;

(4) a VH sequence of SEQ ID NO: 189 and a VL sequence of SEQ ID NO: 190;

(5) a VH sequence of SEQ ID NO: 227 and a VL sequence of SEQ ID NO: 228;

(6) a VH sequence of SEQ ID NO: 265 and a VL sequence of SEQ ID NO: 266;

(7) a VH sequence of SEQ ID NO: 303 and a VL sequence of SEQ ID NO: 304;

(8) a VH sequence of SEQ ID NO: 341 and a VL sequence of SEQ ID NO: 342;

(9) a VH sequence of SEQ ID NO: 379 and a VL sequence of SEQ ID NO: 380;

(10) a VH sequence of SEQ ID NO: 417 and a VL sequence of SEQ ID NO: 418;

(11) a VH sequence of SEQ ID NO: 455 and a VL sequence of SEQ ID NO: 456;

(12) a VH sequence of SEQ ID NO: 493 and a VL sequence of SEQ ID NO: 494;

(13) a VH sequence of SEQ ID NO: 531 and a VL sequence of SEQ ID NO: 532;

(14) a VH sequence of SEQ ID NO: 569 and a VL sequence of SEQ ID NO: 570;

(15) a VH sequence of SEQ ID NO: 607 and a VL sequence of SEQ ID NO: 608;

(16) a VH sequence of SEQ ID NO: 645 and a VL sequence of SEQ ID NO: 646;

(17) a VH sequence of SEQ ID NO: 683 and a VL sequence of SEQ ID NO: 684;

(18) a VH sequence of SEQ ID NO: 721 and a VL sequence of SEQ ID NO: 722; or

(19) a VH sequence of SEQ ID NO: 759 and a VL sequence of SEQ ID NO: 760.

508 . The antibody of claim 504 , wherein the antibody is human, humanized, or chimeric.

509 . The antibody of claim 504 , wherein the antibody is a monoclonal antibody.

510 . The antibody of claim 504 , wherein the antibody is a Fab, Fab′, F(ab′)2, Fv, scFv, (scFv)2, single chain antibody molecule, dual variable domain antibody, linear antibody, or V domain antibody.

511 . The antibody of claim 504 , wherein the antibody comprises an Fc region.

512 . The antibody of claim 504 , wherein the antibody comprises a heavy chain constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

513 . The antibody of claim 504 , wherein the antibody comprises a heavy chain constant region of the class IgG and a subclass selected from IgG1, IgG2, IgG3, and IgG4.

514 . An isolated polynucleotide or set of polynucleotides encoding the antibody of claim 504 , a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof.

515 . A vector or set of vectors comprising the polynucleotide or set of polynucleotides of claim 514 .

516 . A host cell comprising the polynucleotide or set of polynucleotides of claim 514 .

517 . A method of producing an antibody comprising expressing the antibody with the host cell of claim 516 and isolating the expressed antibody.

518 . A pharmaceutical composition comprising the antibody of claim 504 and a pharmaceutically acceptable excipient.

519 . A kit comprising

(i) the antibody of claim 504 ; and

(ii) instructions for use.