Antigen binding protein constructs and uses thereof

Abstract

To provide antigen binding protein constructs and uses thereof.SOLUTION: In this application, an antigen binding protein construct capable of specifically binding to MET or MET epitope presented on the surface of a target mammalian cell is provided, where the binding to the antigen is pH dependent. Also provided is the use of the antigen binding protein construct. The invention is based on a concept that antigen-binding protein constructs can be generated that display enhanced efficacy (e.g., one or more of an increase (e.g., a detectable increase) in toxin liberation in a target mammalian cell, an increase (e.g., a detectable increase) in target mammalian cell killing, and an increase (e.g., a detectable increase) in endolysosomal delivery).SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 880,449, filed July 30, 2019, the contents of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates to the field of biotechnology, and more particularly to antigen-binding molecules. [Background technology]

[0003] Antibody-drug conjugates have been designed to address a variety of diseases. One particular advantage of this approach is the ability of antibody-drug conjugates to have cytostatic or cytotoxic effects. Despite years of development, improvements in antibody-drug conjugates are desirable. Summary of the Invention

[0004] The present invention is based on the concept that antigen binding protein constructs can be generated that exhibit improved efficacy (e.g., one or more of increased (e.g., detectable increase) toxin release in target mammalian cells, increased (e.g., detectable increase) killing of target mammalian cells, and increased (e.g., detectable increase) endolysosomal delivery).

[0005] Provided herein is a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the ABPC comprising a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or (b) the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is D ) at pH 7.0 to 8.0 D The pharmaceutical composition is provided in a form greater than or equal to 1000 mg / kg.

[0006] In some embodiments of any of the pharmaceutical compositions described herein, ABPC is degraded in the target mammalian cells following internalization of ABPC by the target mammalian cells.

[0007] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0008] Also provided herein is a pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC), the ABPC comprising: a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the dissociation rate of the first antigen-binding domain at about pH 4.0 to about 6.5 is faster than the dissociation rate at about pH 7.0 to about 8.0, or the dissociation constant (K) of the first antigen-binding domain at about pH 4.0 to about 6.5 is greater than the dissociation rate at about pH 7.0 to about 8.0. D ) is K at pH 7.0 to 8.0 D and (b) the composition provides one or more of: increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0009] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain of telisotuzumab wherein one or more amino acids are substituted with histidine, wherein the heavy chain variable domain of telisotuzumab comprises SEQ ID NO: 1; and / or a light chain variable domain of telisotuzumab wherein one or more amino acids are substituted with histidine, wherein the light chain variable domain of telisotuzumab comprises SEQ ID NO: 2; (b) a heavy chain variable domain of emibetuzumab wherein one or more amino acids are substituted with histidine, wherein the heavy chain variable domain of emibetuzumab comprises SEQ ID NO: 146; and / or a light chain variable domain of emibetuzumab wherein one or more amino acids are substituted with histidine. (c) a heavy chain variable domain of hucMET27Gv1.3 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 304; and / or a light chain variable domain of hucMET27Gv1.3 wherein one or more amino acids are substituted with histidine, said light chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 305; and (d) a heavy chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain of P3D12 comprising SEQ ID NO: 502; and / or a light chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said light chain variable domain of P3D12 comprising SEQ ID NO: 503.

[0010] In some embodiments of any of the pharmaceutical compositions described herein, the first MET-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NOS: 3 to 5, respectively, wherein the CDR1, CDR2, and CDR3 are collectively substituted with histidine at one or more amino acid positions in SEQ ID NOS: 3 to 5; and / or (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 having SEQ ID NOS: 6 to 8, respectively, wherein the CDR1, CDR2, and CDR3 are substituted with histidine at one or more amino acid positions in SEQ ID NOS: 6 to 8. (b) a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which has one or more amino acid positions substituted with histidine in total; (c) a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which has one or more amino acid positions substituted with histidine in total in SEQ ID NOs: 148 to 150; and / or a heavy ...51 to 153. (c) a light chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 151 to 153, respectively, substituted with histidine at one or more amino acid positions in total; (d) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 306 to 308, respectively, substituted with histidine at one or more amino acid positions in total in SEQ ID NOs: 306 to 308; and / or (d) a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 309 to 311, wherein one or more amino acid positions in total are substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 504 to 506, respectively, wherein one or more amino acid positions in total are substituted with histidine;and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, respectively, of SEQ ID NOS: 507 to 509, wherein a total of one or more amino acid positions in SEQ ID NOS: 507 to 509 have been substituted with histidine;

[0011] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of the following (a)-(d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, and 107; , 36, 37, 54, 55, 59, 60, 95, 99, and 101; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 146, and that comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO: 147, (c) a light chain variable domain comprising a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97; (d) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 304, comprising: 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 104; a heavy chain variable domain comprising a histidine at one or more positions in SEQ ID NO: 304 selected from the group consisting of: 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO: 305 and comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of: 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101;and (d) a heavy chain variable domain at least 90% identical to SEQ ID NO: 502, comprising a histidine at one or more positions in SEQ ID NO: 502 selected from the group consisting of 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101, 102, 103, 106, and 107; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 503, comprising a histidine at one or more positions in SEQ ID NO: 503 selected from the group consisting of 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98;

[0012] In some embodiments of any of the pharmaceutical compositions described herein, the first antigen-binding domain comprises one of the following (a) to (d): (a) SEQ ID NO: 2, SEQ ID NO: 52, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, or SEQ ID NO:140, and / or a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:94, or SEQ ID NO:111, wherein the first antigen-binding domain comprises (i) a light chain variable domain of SEQ ID NO:2 (i) a light chain variable domain and / or a heavy chain variable domain of SEQ ID NO: 1, (ii) a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain other than one of SEQ ID NOs: 13 to 16, 19, 40 to 46, 50, 82 to 84, 86, 87, 89, 90, 94, and 111, or (iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain other than one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; (b) a light chain variable domain and / or a heavy chain variable domain of SEQ ID NO: 2, which does not contain a heavy chain variable domain other than one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; a light chain variable domain of sequence number 147, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:194, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:300, or SEQ ID NO:301;and / or SEQ ID NO:146, SEQ ID NO:159, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:187, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO 234, 235, or 236, wherein the first antigen-binding domain does not (i) comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain of SEQ ID NO: 146, (ii) comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164 to 168, 170, 171, 173, 182 to 184, 187, 217 to 228, and 230 to 236, or (iii) comprise a heavy chain variable domain of SEQ ID NO: 146 and a heavy chain variable domain that is not one of SEQ ID NOs: 190, 191, 194, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 234, 235, or 236, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164 to 168, 170, 171, 173, 182 to 184, 187, 217 to 228, and 230 to 236 (c) the light chain variable domain and / or the heavy chain variable domain does not contain a light chain variable domain other than one of SEQ ID NO: 305, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 360, SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 365, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 374, SEQ ID NO: 378, SEQ ID NO: 380, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430, SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436, SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, SEQ ID NO: 441, SEQ ID NO: 442, SEQ ID NO: 443, SEQ ID NO: 444, SEQ ID NO: 445, SEQ ID NO: 446, SEQ ID NO: 447, SEQ ID NO: 448, SEQ ID NO: 449, SEQ ID NO: 450, SEQ ID NO: 451, SEQ ID NO: 452, SEQ ID NO: 453, SEQ ID NO: 454, SEQ ID NO: 455, SEQ ID NO: 456, SEQ ID NO: 457, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 460, SEQ ID 1, SEQ ID NO:432, SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:450, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:457, SEQ ID NO:462, SEQ ID NO:463, SEQ ID NO:465, SEQ ID NO:470, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:476, SEQ ID NO:479, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:485a light chain variable domain of SEQ ID NO:490, SEQ ID NO:492, SEQ ID NO:494, SEQ ID NO:496, or SEQ ID NO:499, and / or SEQ ID NO:304, SEQ ID NO:313, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:345, SEQ ID NO:347, SEQ ID NO:38 1, a heavy chain variable domain of SEQ ID NO: 382, ​​SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388, SEQ ID NO: 389, SEQ ID NO: 390, SEQ ID NO: 392, SEQ ID NO: 393, SEQ ID NO: 395, SEQ ID NO: 396, SEQ ID NO: 397, SEQ ID NO: 398, SEQ ID NO: 399, or SEQ ID NO: 400, wherein the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 304, or (ii) a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 313, 320 to 324, 32 or (iii) a heavy chain variable domain of SEQ ID NO: 304 and a heavy chain variable domain other than one of SEQ ID NOs: 352, 356, 357, 360, 362, 364, 365, 367, 368, 371, 372, 374, 378, 380, 428 to 446, 450, 451, 453, 457, 462, 463, 465, 470, 472 to 474, 476, 479, 482, 483, 485, 490, 492, 494, 496, and 499. and (d) a light chain variable domain that is not one of SEQ ID NO:503, SEQ ID NO:550, SEQ ID NO:554, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:562, SEQ ID NO:565, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701,a light chain variable domain of SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ ID NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, or SEQ ID NO:732, and / or a light chain variable domain of SEQ ID NO:502, SEQ ID NO:511, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, No. 522, SEQ ID NO: 523, SEQ ID NO: 527, SEQ ID NO: 529, SEQ ID NO: 538, SEQ ID NO: 540, SEQ ID NO: 541, SEQ ID NO: 542, SEQ ID NO: 543, SEQ ID NO: 546, SEQ ID NO: 547, SEQ ID NO: 578, SEQ ID NO: 579, SEQ ID NO: 580, SEQ ID NO: 581, SEQ ID NO: 582, SEQ ID NO: 583, SEQ ID NO: 584, SEQ ID NO: 585, SEQ ID NO: 586, SEQ ID NO: 587, SEQ ID NO: 588, SEQ ID NO: 589, SEQ ID NO: 590, SEQ ID NO: 591, SEQ ID NO: 592 , SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 606, SEQ ID NO: 621, SEQ ID NO: 659, or SEQ ID NO: 676, wherein the first antigen-binding domain does not include (i) a light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain of SEQ ID NO: 502, or (ii) a light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain of SEQ ID NO: 511, 513, 514, 516 to 523, 527, 529, 538 , 540 to 543, 546, 547, 578 to 597, 606, 621, 659, and 676, or (iii) does not contain a heavy chain variable domain of SEQ ID NO: 502 and a light chain variable domain other than one of SEQ ID NOs: 550, 554, 556 to 560, 562, 565, 569, 570 to 576, 697 to 713, and 732.

[0013] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC, and / or increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0014] In some embodiments of any of the pharmaceutical compositions described herein, the composition provides increased endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0015] In some embodiments of any of the pharmaceutical compositions described herein, the composition does not cause a significant decrease in the level of MET present on the surface of target mammalian cells, or does not produce a detectable decrease in the level of MET present on the surface of target mammalian cells, compared to a composition comprising the same amount of control ABPC.

[0016] In some embodiments of any of the pharmaceutical compositions described herein, the target mammalian cell is a cancer cell.

[0017] In some embodiments of any pharmaceutical composition described herein, ABPC is cytotoxic or cytostatic to target mammalian cells.In some embodiments of any pharmaceutical composition described herein, ABPC is cross-reactive with non-human primate MET and human MET, or cross-reactive with one or both of non-human primate MET, human MET, and rat MET and mouse MET.

[0018] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a single polypeptide. In some embodiments of any of the pharmaceutical compositions described herein, the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the pharmaceutical compositions described herein, the ABPC is an antibody.

[0019] In some embodiments of any of the pharmaceutical compositions described herein, the half-life of ABPC in vivo is decreased compared to the half-life of control ABPC in vivo.

[0020] In some embodiments of any of the pharmaceutical compositions described herein, the ABPC comprises a second antigen-binding domain.

[0021] Provided herein is an antigen-binding protein construct (ABPC), comprising a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or (b) the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is D ) at pH 7.0 to 8.0 D Antigen binding protein constructs (ABPCs) are provided that are larger than

[0022] In some embodiments of any of the ABPCs described herein, the ABPC is degraded in the target mammalian cells following internalization of the ABPC by the target mammalian cells.

[0023] In some embodiments of any of the ABPCs described herein, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0024] Also provided herein is an antigen-binding protein construct (ABPC), comprising: a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0. D ) is K at pH 7.0 to 8.0 Dand (b) the composition provides one or more of: increased toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0025] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises one of the following (a)-(d): (a) a heavy chain variable domain of telisotuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 1; and / or a light chain variable domain of telisotuzumab, wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 2; (b) a heavy chain variable domain of emibetuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 146; and / or a light chain variable domain of emibetuzumab, wherein one or more amino acids are substituted with histidine. (c) a heavy chain variable domain of hucMET27Gv1.3 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 304; and / or a light chain variable domain of hucMET27Gv1.3 wherein one or more amino acids are substituted with histidine, said light chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 305; and (d) a heavy chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said heavy chain variable domain of P3D12 comprising SEQ ID NO: 502; and / or a light chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said light chain variable domain of P3D12 comprising SEQ ID NO: 503.

[0026] In some embodiments of any of the ABPCs described herein, the first MET-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, which are SEQ ID NOS: 3 to 5, respectively, and which collectively have one or more amino acid positions substituted with histidine in total; and / or CDR1, CDR2, and CDR3, which are SEQ ID NOS: 6 to 8, respectively, and which collectively have one or more amino acid positions substituted with histidine in total in SEQ ID NOS: 6 to 8. (b) a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which has one or more amino acid positions substituted with histidine in total; (c) a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which has one or more amino acid positions substituted with histidine in total in SEQ ID NOs: 148 to 150; and / or a heavy ...51 to 153. (c) a light chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 151 to 153, respectively, substituted with histidine at one or more amino acid positions in total; (d) a heavy chain variable domain comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 306 to 308, respectively, substituted with histidine at one or more amino acid positions in total in SEQ ID NOs: 306 to 308; and / or (d) a light chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 309 to 311, wherein one or more amino acid positions in total are substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 504 to 506, respectively, wherein one or more amino acid positions in total are substituted with histidine;and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, respectively, of SEQ ID NOS: 507 to 509, wherein a total of one or more amino acid positions in SEQ ID NOS: 507 to 509 have been substituted with histidine;

[0027] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises one of the following (a)-(d): (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 146, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 31, 50, 51, 52, 53, 54, 55, 59, 60, 95, 99, and 101; 147, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of: 25, 26, 29, 32, 33, 51, 91, 92, 95, 96 and 97; and / or a light chain variable domain that is at least 90% identical to SEQ ID NO: 147, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of: 25, 26, 29, 32, 33, 51, 91, 92, 95, 96 and 97. (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 304 and that comprises a histidine at one or more positions in SEQ ID NO: 304 selected from the group consisting of 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 105;and / or a light chain variable domain which is at least 90% identical to SEQ ID NO: 305 and which comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99 and 101, and (d) a heavy chain variable domain which is at least 90% identical to SEQ ID NO: 502 and which comprises 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101 a heavy chain variable domain comprising a histidine at one or more positions in SEQ ID NO: 502 selected from the group consisting of 01, 102, 103, 106, and 107; and / or a light chain variable domain which is at least 90% identical to SEQ ID NO: 503 and comprises a histidine at one or more positions in SEQ ID NO: 503 selected from the group consisting of 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98;

[0028] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises one of the following (a) to (d): (a) SEQ ID NO: 2, SEQ ID NO: 52, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO:138, SEQ ID NO:139, or SEQ ID NO:140, and / or a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:94, or SEQ ID NO:111, wherein the first antigen-binding domain comprises (i) a light chain variable domain of SEQ ID NO:2 (ii) the light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain other than one of SEQ ID NOs: 13 to 16, 19, 40 to 46, 50, 82 to 84, 86, 87, 89, 90, 94, and 111, or (iii) the heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain other than one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; (b) the light chain variable domain and / or the heavy chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain other than one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; a light chain variable domain of SEQ ID NO:147, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:194, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:300, or SEQ ID NO:301;and / or SEQ ID NO:146, SEQ ID NO:159, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:187, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO 234, 235, or 236, wherein the first antigen-binding domain does not (i) comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain of SEQ ID NO: 146, (ii) comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164 to 168, 170, 171, 173, 182 to 184, 187, 217 to 228, and 230 to 236, or (iii) comprise a heavy chain variable domain of SEQ ID NO: 146 and a heavy chain variable domain that is not one of SEQ ID NOs: 190, 191, 194, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 234, 235, or 236, (c) the light chain variable domain and / or the heavy chain variable domain does not comprise a light chain variable domain other than one of SEQ ID NO: 305, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 360, SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 365, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 374, SEQ ID NO: 378, SEQ ID NO: 380, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430, SEQ ID NO: 431, SEQ ID NO: 43 2, SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:450, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:457, SEQ ID NO:462, SEQ ID NO:463, SEQ ID NO:465, SEQ ID NO:470, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:476, SEQ ID NO:479, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:485, SEQ ID NO:490,a light chain variable domain of SEQ ID NO:492, SEQ ID NO:494, SEQ ID NO:496, or SEQ ID NO:499, and / or SEQ ID NO:304, SEQ ID NO:313, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:345, SEQ ID NO:347, SEQ ID NO:381, SEQ ID NO:3 82, SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388, SEQ ID NO: 389, SEQ ID NO: 390, SEQ ID NO: 392, SEQ ID NO: 393, SEQ ID NO: 395, SEQ ID NO: 396, SEQ ID NO: 397, SEQ ID NO: 398, SEQ ID NO: 399, or SEQ ID NO: 400, wherein the first antigen-binding domain is (i) not including a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 304, (ii) not including a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 313, 320 to 324, 326 to 337, 34 or (iii) a heavy chain variable domain of SEQ ID NO: 304 and a light chain variable domain other than one of SEQ ID NOs: 352, 356, 357, 360, 362, 364, 365, 367, 368, 371, 372, 374, 378, 380, 428 to 446, 450, 451, 453, 457, 462, 463, 465, 470, 472 to 474, 476, 479, 482, 483, 485, 490, 492, 494, 496, and 499. and (d) the light chain variable domain and / or the heavy chain variable domain, each of which does not comprise a chain variable domain, and (e) SEQ ID NO:503, SEQ ID NO:550, SEQ ID NO:554, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:562, SEQ ID NO:565, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703,the light chain variable domain of SEQ ID NO:704, SEQ ID NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, or SEQ ID NO:732, and / or the light chain variable domain of SEQ ID NO:502, SEQ ID NO:511, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, SEQ ID NO:522, SEQ ID NO: 523, SEQ ID NO:527, SEQ ID NO:529, SEQ ID NO:538, SEQ ID NO:540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:546, SEQ ID NO:547, SEQ ID NO:578, SEQ ID NO:579, SEQ ID NO:580, SEQ ID NO:581, SEQ ID NO:582, SEQ ID NO:583, SEQ ID NO:584, SEQ ID NO:585, SEQ ID NO:586, SEQ ID NO:587, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:590, SEQ ID NO:591, SEQ ID NO:592, SEQ ID NO: a heavy chain variable domain of SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 606, SEQ ID NO: 621, SEQ ID NO: 659, or SEQ ID NO: 676, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain of SEQ ID NO: 502, or (ii) a light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain of SEQ ID NO: 511, 513, 514, 516 to 523, 527, 529, 538 , 540 to 543, 546, 547, 578 to 597, 606, 621, 659, and 676, or (iii) the light chain variable domain and / or the heavy chain variable domain does not contain a heavy chain variable domain of SEQ ID NO: 502 and a light chain variable domain other than one of 550, 554, 556 to 560, 562, 565, 569, 570 to 576, 697 to 713, and 732.

[0029] In some embodiments of any of the ABPCs described herein, a composition comprising ABPC provides increased toxin release in target mammalian cells compared to a composition comprising an equivalent amount of control ABPC, and / or increased killing of target mammalian cells compared to a composition comprising an equivalent amount of control ABPC.

[0030] In some embodiments of any of the ABPCs described herein, a composition comprising ABPC provides increased endolysosomal delivery in target mammalian cells compared to a composition comprising an equal amount of control ABPC.

[0031] In some embodiments of any of the ABPCs described herein, a composition comprising ABPC does not result in a significant decrease in the level of MET present on the surface of target mammalian cells, or does not result in a detectable decrease in the level of MET present on the surface of target mammalian cells, compared to a composition comprising an equivalent amount of control ABPC.

[0032] In some embodiments of any ABPC described herein, target mammalian cell is cancer cell.In some embodiments of any ABPC described herein, ABPC is cytotoxic or cytostatic to target mammalian cell.In some embodiments of any ABPC described herein, ABPC is cross-reactive with non-human primate MET and human MET, or cross-reactive with one or both of non-human primate MET, human MET, and rat MET and mouse MET.

[0033] In some embodiments of any of the ABPCs described herein, the ABPC comprises a single polypeptide. In some embodiments of any of the ABPCs described herein, the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. In some embodiments of any of the ABPCs described herein, the ABPC comprises two or more polypeptides. In some embodiments of any of the ABPCs described herein, the ABPC is an antibody.

[0034] In some embodiments of any of the ABPCs described herein, the half-life of the ABPC in vivo is decreased compared to the half-life of a control ABPC in vivo.

[0035] In some embodiments of any of the ABPCs described herein, the ABPC comprises a second antigen-binding domain.

[0036] Also provided herein are kits containing any one of the pharmaceutical compositions described herein or at least one dose of any one of the pharmaceutical compositions of ABPC described herein.

[0037] Also provided herein is a method of treating a cancer characterized by having a population of cancer cells that have MET or an epitope of MET present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0038] Also provided herein is a method for reducing tumor volume in a subject, wherein the tumor is characterized by having a population of cancer cells that have MET or an epitope of MET present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having the above-mentioned population of cancer cells.

[0039] Also provided herein is a method of inducing cell death of cancer cells in a subject, wherein the cancer cells have MET or an epitope of MET present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having a population of said cancer cells.

[0040] Also provided herein is a method for reducing the risk of developing metastases or reducing the risk of developing further metastases in a subject having cancer characterized by having a population of cancer cells that have MET or an epitope of MET present on their surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any one of the ABPCs described herein to a subject identified as having a cancer characterized by having the population of cancer cells.

[0041] As used herein, the term "antigen-binding protein construct" refers to (i) a single polypeptide comprising at least one antigen-binding domain, or (ii) a complex of two or more polypeptides (e.g., the same or different polypeptides) that together form at least one antigen-binding domain. Non-limiting examples and embodiments of antigen-binding protein constructs are described herein. Further examples and embodiments of antigen-binding protein constructs are known in the art.

[0042] A "multispecific antigen-binding protein construct" is an antigen-binding protein construct comprising two or more different antigen-binding domains that collectively specifically bind two or more different epitopes. The two or more different epitopes can be epitopes on the same antigen (e.g., a single polypeptide present on the surface of a cell) or on different antigens (e.g., different proteins present on the surface of the same cell or on the surface of different cells). In some aspects, the antigens are present on the surface of a cell. In some aspects, the multispecific antigen-binding protein construct binds to two different epitopes (i.e., a "bispecific antigen-binding protein construct"). In some embodiments, the multispecific antigen-binding protein construct binds to three different epitopes (i.e., a "trispecific antigen-binding protein construct"). In some aspects, the multispecific antigen-binding protein construct binds to four different epitopes (i.e., a "tetraspecific antigen-binding protein construct"). In some aspects, the multispecific antigen-binding protein construct binds to five different epitopes (i.e., a "pentaspecific antigen-binding protein construct"). Each binding specificity may be present in any suitable valency. Non-limiting examples of multispecific antigen-binding protein constructs are described herein.

[0043] An "antigen-binding domain" is one or more protein domains (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides) that can specifically bind to one or more different antigens). In some examples, an antigen-binding domain can bind to an antigen or epitope with specificity and affinity similar to that of a naturally occurring antibody. In some embodiments, an antigen-binding domain may be an antibody or fragment thereof. In some embodiments, an antigen-binding domain may comprise an alternative scaffold. Non-limiting examples of antigen-binding domains are described herein. Further examples of antigen-binding domains are known in the art. In some examples, an antigen-binding domain may bind to a single antigen.

[0044] The term "antibody" is used herein in its broadest sense and includes a specific type of immunoglobulin molecule that contains one or more antigen-binding domains that specifically bind to an antigen or epitope. Antibodies include, for example, intact antibodies (e.g., intact immunoglobulins, such as human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments, and multispecific antibodies, among others. One example of an antigen-binding domain is the antigen-binding domain formed by a VH-VL dimer. Further examples of antibodies are described herein. Further examples of antibodies are known in the art.

[0045] The phrase "endosomal / lysosomal pathway" refers to the network of endosomes (early endosomes, multivesicular bodies, late endosomes, and lysosomes) in the cytoplasm of mammalian cells, where molecules are sorted for internalization via cell-mediated internalization processes, such as pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis.

[0046] Once endosomes in the endosomal / lysosomal pathway have been purified or isolated, assays for the target protein (e.g., the antigen-binding protein constructs described herein) can be performed using methods known in the art (e.g., ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by assays of protein concentration) and can be used to determine the concentration or relative levels of the target protein in the endosomes. Alternatively, endosomes in the endosomal / lysosomal pathway can be imaged by immunofluorescence microscopy using a detectably labeled antibody (e.g., a fluorescently, dye-, or GFP-labeled antibody, e.g., CellLight™ Early Endosome-GFP) that specifically binds to a characteristic protein present in endosomes (e.g., EEA1 in early endosomes) and a fluorescently labeled antibody (e.g., an antigen-binding protein construct) that specifically binds to the protein of interest, and the level of the target protein in the endosomes can be determined by quantifying the overlap of the fluorescence emissions of the two different antibodies.

[0047] The phrase "endolysosomal delivery" refers to the rate of accumulation over time or the total amount accumulated at a particular time point of an antigen binding protein construct (e.g., any of the antigen binding protein constructs described herein) in the endosomal / lysosomal pathway in a mammalian cell (e.g., any of the exemplary target mammalian cells described herein).

[0048] An exemplary method for calculating the increased endolysosomal delivery of a pH-engineered ABPC variant compared to the corresponding starting ABPC from cytofluorescence data is to measure the ratio of the mean fluorescence intensity of the variant minus the mean fluorescence intensity of the non-binding IgG control, and then divide the total by the mean fluorescence intensity of the variant's corresponding starting ABPC minus the mean fluorescence intensity of the IgG control.

[0049] An exemplary assay for measuring endolysosomal delivery of any ABPC described herein includes an assay involving labeling ABPC with a fluorescent dye, followed by incubation of the labeled ABPC with cells, and measuring cellular fluorescence as an indicator of endolysosomal delivery of ABPC (e.g., generally as described in Wustner, Traffic 7(6):699-715, 2006). Alternatively, any ABPC described herein can be labeled with a pH-sensitive dye that is preferentially fluorescent at acidic pH but not at neutral pH, which can then be incubated with cells and cellular fluorescence measured as an indicator of delivery of ABPC to the acidic endolysosomal compartment.

[0050] When the term "population" is used before a noun, it means two or more of that particular noun. For example, the phrase "population of cancer cells" means "two or more cancer cells." Non-limiting examples of cancer cells are described herein.

[0051] The phrase "cytostatic to a cell" refers to a direct or indirect reduction in proliferation (cell division) of the cell (e.g., a cancer cell) in vivo or in vitro. When a therapeutic agent is cytostatic to a cell, the therapeutic agent may, for example, directly or indirectly cause cell cycle arrest of the cell (e.g., a cancer cell). In some examples, a therapeutic agent that is cytostatic to a cell can reduce the number of cells in a population of cells that are in S phase (compared to the number of cells in that population of cells that are in S phase prior to contact with the therapeutic agent). In some examples, a therapeutic agent that is cytostatic to a cell can reduce the percentage of cells in S phase by at least 20%, at least 40%, at least 60%, or at least 80% (e.g., compared to the percentage of cells in a population of cells that are in S phase prior to contact with the therapeutic agent).

[0052] The phrase "cytotoxic to a cell" refers to directly or indirectly inducing death (eg, necrosis or apoptosis) of the cell (eg, a mammalian cell, eg, a cancer cell).

[0053] "Affinity" refers to the strength of the sum total of non-covalent interactions between an antigen-binding site and its binding partner (e.g., antigen or epitope). Unless otherwise indicated, as used herein, "affinity" refers to the intrinsic binding affinity, which reflects a 1:1 interaction between a member of the antigen-binding domain and the antigen or epitope. The affinity of a molecule X for its partner Y is determined by the dissociation equilibrium constant (K D ). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®). Additional methods for determining the affinity of an antigen-binding domain to its corresponding antigen or epitope are known in the art.

[0054] The term "epitope" refers to a portion of an antigen that is specifically bound by an antigen-binding domain through a series of physical interactions between: (i) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen-binding domain that specifically binds to the antigen, and (ii) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen that is specifically bound by the antigen-binding domain. Epitopes may consist of, for example, surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and / or acetylated amino acid residues, and may have specific three-dimensional structural characteristics as well as specific charge characteristics. Conformational and nonconformational epitopes are distinguished in that binding to the former, but not the latter, can be lost in the presence of denaturing solvents. In some embodiments, an epitope is defined by a linear amino acid sequence of at least about 3-6 amino acids, or about 10-15 amino acids. In some embodiments, an epitope refers to a portion of a full-length protein or a portion thereof defined by three-dimensional structure (e.g., protein folding). In some embodiments, an epitope is defined by discontinuous amino acid sequences held together through protein folding. In some embodiments, an epitope is defined by discontinuous amino acid sequences held together by quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues defining the epitope may not be important to the three-dimensional structure of the epitope. Conformational epitopes can be determined and screened using assays comparing the binding of antigen-binding protein constructs to denatured versions of the antigen of interest, so that linear epitopes are generated. Epitopes can include amino acid residues directly involved in binding and other amino acid residues not directly involved in binding.

[0055] Methods for identifying the epitope to which an antigen-binding domain specifically binds are known in the art, such as structural-based analysis (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., of the antigen and / or antigen-antigen binding domain complex), and / or mutagenesis-based analysis in which mutants are measured in binding assays with a binding partner (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), many of which are known in the art.

[0056] The term "paratope" refers to a portion of an antigen-binding domain that specifically binds to an antigen through a series of physical interactions between: (i) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen-binding domain that specifically binds to the antigen, and (ii) all monomers (e.g., individual amino acid residues, sugar side chains, post-translationally modified amino acid residues) on the portion of the antigen that is specifically bound by the antigen-binding domain. A paratope can consist of, for example, surface-accessible amino acid residues and can have specific three-dimensional structural characteristics as well as specific charge characteristics. In some embodiments, a paratope refers to a portion of a full-length antigen-binding domain or a portion thereof that is defined by a three-dimensional structure (e.g., protein folding). In some embodiments, a paratope is defined by discontinuous amino acid sequences held together through protein folding. In some embodiments, an epitope is defined by discontinuous amino acid sequences held together by a quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues that define the paratope may not be important to the three-dimensional structure of the paratope. The paratope can include amino acid residues that are directly involved in binding and other amino acid residues that are not directly involved in binding.

[0057] Methods for identifying the paratope to which an antigen-binding domain specifically binds are known in the art, such as structural-based analysis (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., of the antigen-binding domain and / or antigen-binding domain-antigen complex), and / or mutagenesis-based analysis in which mutants are measured in binding assays with a binding partner (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), many of which are known in the art.

[0058] The phrase "present on the surface of a mammalian cell" refers to (1) an antigen that is physically associated with or at least partially incorporated into the plasma membrane of a mammalian cell (e.g., a transmembrane protein, a peripheral membrane protein, a lipid-binding protein (e.g., a GPI anchor), an N-myristolyated protein, or an S-palmitoylated protein), or (2) an antigen stably bound to its cognate receptor that is physically associated with the plasma membrane of a mammalian cell (e.g., a ligand bound to its cognate receptor, which physically attaches the cognate receptor to the plasma membrane). Non-limiting methods for determining the presence of an antigen on the surface of a mammalian cell include fluorescence-activated cell sorting (FACS), immunohistochemistry, cell fractionation assays, and Western blot.

[0059] The phrase "control ABPC" or "control antigen-binding protein construct" refers to an ABPC that (i) is capable of specifically binding to MET or an epitope of MET present on the surface of a mammalian cell (e.g., a target mammalian cell), and (a) has a dissociation rate of its first antigen-binding domain at a pH of about 4.0 to about 6.5 (e.g., any subrange of this range described herein) that is 3 times slower than its dissociation rate at a pH of about 7.0 to about 8.0 (e.g., any subrange of this range described herein). fold or less (e.g., 2.8-fold or less, 2.6-fold or less, 2.5-fold or less, 2.4-fold or less, 2.2-fold or less, 2.0-fold or less, 1.8-fold or less, 1.6-fold or less, 1.5-fold or less, 1.4-fold or less, 1.2-fold or less, 1.0-fold or less, 0.8-fold or less, 0.6-fold or less, 0.5-fold or less, 0.4-fold or less, 0.3-fold or less, 0.2-fold or less, or 0.1-fold or less), or (b) the dissociation constant (K D ) at a pH of about 7.0 to about 8.0 (e.g., any of the subranges of this range described herein). D and / or (ii) telisotuzumab, and / or (iii) emibetuzumab, and / or (iv) hucMET27Gv1.3, and / or (v) P3D12 (Tanabe Pharmaceuticals), which are 3-fold or less (e.g., 2.8-fold or less, 2.6-fold or less, 2.5-fold or less, 2.4-fold or less, 2.2-fold or less, 2.0-fold or less, 1.8-fold or less, 1.6-fold or less, 1.5-fold or less, 1.4-fold or less, 1.2-fold or less, 1.0-fold or less, 0.8-fold or less, 0.6-fold or less, 0.5-fold or less, 0.4-fold or less, 0.3-fold or less, 0.2-fold or less, or 0.1-fold or less) greater than the ABPC.

[0060] The term "extracellular space" refers to the fluid outside the plasma membrane of a mammalian cell. When the mammalian cell is in vitro, the extracellular space can be liquid culture medium. When the mammalian cell is in vivo, the extracellular space can be, for example, plasma, serum, blood, interstitial fluid, or lymph.

[0061] The term "endolysosomal space" refers to the fluid enclosed by the vesicles and organelles that make up the endosomal / lysosomal pathway in mammalian cells.

[0062] The phrase "reduced level" or "decreased level" can be a reduction or decrease that is a reduction of at least 1% (e.g., at least 2%, at least 4%, at least 6%, at least 8%, at least 10%, at least 12%, at least 14%, at least 16%, at least 18%, at least 20%, at least 22%, at least 24%, at least 26%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99%) as compared to a reference level or value.

[0063] The term "cell killing ability" refers to the ability of a drug (e.g., any ABPC described herein) to directly or indirectly induce apoptosis and / or necrosis in mammalian cells (e.g., cancer cells), measured as a rate over time or at relevant time points. Methods for determining the cell killing ability of a cell are known in the art (e.g., trypan blue staining, microscopy, fluorescence-assisted cell sorting, and assays detecting apoptosis markers (e.g., Annexin V)). In non-limiting examples, cell killing ability can be measured, for example, by cell killing at a single drug concentration, by the drug's IC50 (i.e., the drug concentration that achieves half of the maximum cell killing ability), or by the ratio of the drug's dissociation constant KD in mammalian cells divided by its IC50. In some non-limiting examples, the IC50 and / or KD ratio described herein are compared with those of a control ABPC (as defined herein), and optionally demonstrate that the ABPC described herein has a higher cell killing ability than the control ABPC.

[0064] The term "toxin release" refers to the ability of mammalian cells (e.g., non-cancerous mammalian cells or cancer cells) to internalize (e.g., via pinocytosis and / or receptor-mediated endocytosis) any of the ABPCs described herein (e.g., any of the ABPCs described herein or control ABPCs) conjugated to a toxin, and then release the toxin conjugated to the ABPC, measured as a percentage over time or at specific time points. Toxin release can be assessed using a variety of different exemplary assays, such as ELISA, immunofluorescence, cell killing assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and / or isotope-labeled toxins.

[0065] The phrases "target cell" or "target mammalian cell" or "mammalian target cell" refer to mammalian cells having at least one MET present on their surface. In some examples, the mammalian target cell can be a cancer cell. In some embodiments of the target mammalian cell, a total of about 1 to about 10,000,000, about 1 to about 9,000,000, about 1 to about 8,000,000, about 1 to about 7,000,000, about 1 to about 6,000,000, about 1 to about 5,000,000, about 1 to about 4,000,000, about 1 to about 3,000,000, about 1 to about 2,000,000, about 1 to about 1,000,000, about 1 to about 800,000, about 1 to about 600,000, about 1 to about 400,000, about 1 to about 200,000, about 1 to about 100,000, about 1 to about 80,000, about 1 to about 80,000, about 1 to about 75,000, about 1 to about 70,000, about 1 to about 65,000, about 1 to about 60,000, about 1 to about 55,000, about 1 to about 50,000, about 1 to about 45,000, about 1 to about 40,000, about 1 to about 35,000, about 1 to about 30,000, about 1 to about 25,000, about 1 to about 20,000, about 1 to about 15,000, about 1 to about 10,000, about 1 to about 7,500, about 1 to about 5,000, about 1 to about 4,000, about 1 to about 3,000, about 1 to about 2,000, about 1 to about 1,000, about 1 to about 500, about 1 to about 100, about 1 to about 50, about 1 to about 10, about 10 to about 10,000,000, about 10 to about 9,000,000, about 10 to about 8,000,000, about 10 to about 7,000,000 6,000,000, about 10 to about 5,000,000, about 10 to about 4,000,000, about 10 to about 3,000,000, about 10 to about 2,000,000, about 10 to about 1,000,000, about 10 to about 800,000, about 10 to about 600,000, about 10 to about 400,000, about 10 to about 200,000, about 10 to about 100,000, about 10 to about 80,000, about 10 to about 80,000, about 10 to about 75,000, about 10 to about 70,000, about 10 to about 65,000, about 10 to about 60,000, about 10 to about 55,000, about 10 to about 50,000, about 10 to about 45,000, about 10 to about 40,000, about 10 to about 35,000, about 10 to about 30,000, about 10 to about 25,000, about 10 to about 20,000, about 10 to about 15,000, about 10 to about 10,000, about 10 to about 7,500, about 10 to about 5,000, about 10 to about 4,000, about 10 to about 3,000, about 10 to about 2,000, about 10 to about 1,000 0, about 10 to about 500, about 10 to about 100, about 10 to about 50, about 50 to about 10,000,000, about 50 to about 9,000,000, about 50 to about 8,000,000, about 50 to about 7,000,000, about 50 to about 6,000,000, about 50 to about 5,000,000, about 50 to about 4,000,000, about 50 to about 3,000,000, about 50 to about 2,000,000, about 50 to about 1,000,000, about 50 to about 800,000, about 50 to about 600,000, about 50 to about 400,000 0, about 50 to about 200,000, about 50 to about 100,000, about 50 to about 80,000, about 50 to about 80,000, about 50 to about 75,000, about 50 to about 70,000, about 50 to about 65,000, about 50 to about 60,000, about 50 to about 55,000, about 50 to about 50,000, about 50 to about 45,000, about 50 to about 40,000, about 50 to about 35,000, about 50 to about 30,000, about 50 to about 25,000, about 50 to about 20,000, about 50 to about 15,000, about 50 to about 10,000, about 50 to about 7,500, about 50 to about 5,000, about 50 to about 4,000, about 50 to about 3,000, about 50 to about 2,000, about 50 to about 1,000, about 50 to about 500, about 50 to about 100, about 100 to about 10,000,000, about 100 to about 9,000,000, about 100 to about 8,000,000, about 100 to about 7,000,000, about 100 to about 6,000,000, about 100 to about 5,000,000, about 100 to about 4,000,000, about 100 to about 3,000,000, about 100 to about 2,000,000, about 100 to about 1,000,000, about 100 to about 800,000, about 100 to about 600,000, about 100 to about 400,000, about 100 to about 200,000, about 100 to about 100,000, about 100 to about 80,000, about 100 to about 75,000, about 100 to about 70,000, about 100 to about 65,000, about 100 to about 60,000, about 100 to about 55,000, about 100 to about 50,000, about 100 to about 45,000, about 100 to about 40,000, about 100 to about 35,000, about 100 to about 30,000, about 100 to about 25,000, about 100 to about 20,000, about 100 to about 15,000, about 100 to about 10,000, about 100 to about 7,500, about 100 to about 5,000, about 100 to about 4,000, about 100 to about 3,000, about 100 to about 2,000, about 100 to about 1,000, about 100 to about 500, about 500 to about 10,000,000, about 500 to about 9,000,000, about 500 to about 8,000,000 , about 500 to about 7,000,000, about 500 to about 6,000,000, about 500 to about 5,000,000, about 500 to about 4,000,000, about 500 to about 3,000,000, about 500 to about 2,000,000, about 500 to about 1,000,000, about 500 to about 800,000, about 500 to about 600,000, about 500 to about 400,000, about 500 to about 200,000, about 500 to about 100,000, about 500 to about 80,000, about 500 to about 75,000, about 500 to about 70,000 00, about 500 to about 65,000, about 500 to about 60,000, about 500 to about 55,000, about 500 to about 50,000, about 500 to about 45,000, about 500 to about 40,000, about 500 to about 35,000, about 500 to about 30,000, about 500 to about 25,000, about 500 to about 20,000, about 500 to about 15,000, about 500 to about 10,000, about 500 to about 7,500, about 500 to about 5,000, about 500 to about 4,000, about 500 to about 3,000, about 500 to about 2,000, about 500 to about 1,000, about 1,000 to about 10,000,000, about 1,000 to about 9,000,000, about 1,000 to about 8,000,000, about 1,000 to about 7,000,000, about 1,000 to about 6,000,000, about 1,000 to about 5,000,000, about 1,000 to about 4,000,000, about 1,000 to about 3,000,000, about 1,000 to about 2,000,000, about 1,000 to about 1,000,000, about 1,000 to about 800,000, about 1,000 to about 60 0,000, about 1,000 to about 400,000, about 1,000 to about 200,000, about 1,000 to about 100,000, about 1,000 to about 80,000, about 1,000 to about 75,000, about 1,000 to about 70,000, about 1,000 to about 65,000, about 1,000 to about 60,000, about 1,000 to about 55,000, about 1,000 to about 50,000, about 1,000 to about 45,000, about 1,000 to about 40,000, about 1,000 to about 35,000, about 1,000 to about 30,000, about 1 ,000 to about 25,000, about 1,000 to about 20,000, about 1,000 to about 15,000, about 1,000 to about 10,000, about 1,000 to about 7,500, about 1,000 to about 5,000, about 1,000 to about 4,000, about 1,000 to about 3,000, about 1,000 to about 2,000, about 2,000 to about 10,000,000, about 2,000 to about 9,000,000, about 2,000 to about 8,000,000, about 2,000 to about 7,000,000, about 2,000 to about 6,000,000, 000 to about 5,000,000, about 2,000 to about 4,000,000, about 2,000 to about 3,000,000, about 2,000 to about 2,000,000, about 2,000 to about 1,000,000, about 2,000 to about 800,000, about 2,000 to about 600,000, about 2,000 to about 400,000, about 2,000 to about 200,000, about 2,000 to about 100,000, about 2,000 to about 80,000, about 2,000 to about 75,000, about 2,000 to about 70,000, about 2,000 to about 65,000, about 2,000 to about 60,000, about 2,000 to about 55,000, about 2,000 to about 50,000, about 2,000 to about 45,000, about 2,000 to about 40,000, about 2,000 to about 35,000, about 2,000 to about 30,000, about 2,000 to about 25,000, about 2,000 to about 20,000, about 2,000 to about 15,000, about 2,000 to about 10,000, about 2,000 to about 7,500, about 2,000 to about 5,000, about 2,000 to about 4,000, about 2,000 to about About 3,000, about 3,000 to about 10,000,000, about 3,000 to about 9,000,000, about 3,000 to about 8,000,000, about 3,000 to about 7,000,000, about 3,000 to about 6,000,000, about 3,000 to about 5,000,000, about 3,000 to about 4,000,000, about 3,000 to about 3,000,000, about 3,000 to about 2,000,000, about 3,000 to about 1,000,000, about 3,000 to about 800,000, about 3,000 to about 600,000, about 3,000 00 to about 400,000, about 3,000 to about 200,000, about 3,000 to about 100,000, about 3,000 to about 80,000, about 3,000 to about 75,000, about 3,000 to about 70,000, about 3,000 to about 65,000, about 3,000 to about 60,000, about 3,000 to about 55,000, about 3,000 to about 50,000, about 3,000 to about 45,000, about 3,000 to about 40,000, about 3,000 to about 35,000, about 3,000 to about 30,000, about 3,000 to about 25 ,000, about 3,000 to about 20,000, about 3,000 to about 15,000, about 3,000 to about 10,000, about 3,000 to about 7,500, about 3,000 to about 5,000, about 3,000 to about 4,000, about 4,000 to about 10,000,000, about 4,000 to about 9,000,000, about 4,000 to about 8,000,000, about 4,000 to about 7,000,000, about 4,000 to about 6,000,000, about 4,000 to about 5,000,000, about 4,000 to about 4,000,000,000 to about 3,000,000, about 4,000 to about 2,000,000, about 4,000 to about 1,000,000, about 4,000 to about 800,000, about 4,000 to about 600,000, about 4,000 to about 400,000, about 4,000 to about 200,000, about 4,000 to about 100,000, About 4,000 to about 80,000, about 4,000 to about 75,000, about 4,000 to about 70,000, about 4,000 to about 65,000, about 4,000 to about 60,000, about 4,000 to about 55,000, about 4,000 to about 50,000, about 4,000 to about 45,000, about 4,000 to about 40,000, about 4,000 to about 35,000, about 4,000 to about 30,000, about 4,000 to about 25,000, about 4,000 to about 20,000, about 4,000 to about 15,000, about 4,000 to about 10, 000, about 4,000 to about 7,500, about 4,000 to about 5,000, about 5,000 to about 10,000,000, about 5,000 to about 9,000,000, about 5,000 to about 8,000,000, about 5,000 to about 7,000,000, about 5,000 to about 6,000,000, about 5,000 to about 5,000,000, about 5,000 to about 4,000,000, about 5,000 to about 3,000,000, about 5,000 to about 2,000,000, about 5,000 to about 1,000,000, about 5,000 to about 800 ,000, about 5,000 to about 600,000, about 5,000 to about 400,000, about 5,000 to about 200,000, about 5,000 to about 100,000, about 5,000 to about 80,000, about 5,000 to about 75,000, about 5,000 to about 70,000, about 5,000 to about 65,000, about 5,000 to about 60,000, about 5,000 to about 55,000, about 5,000 to about 50,000, about 5,000 to about 45,000, about 5,000 to about 40,000, about 5,000 to about 35,000, about 5 ,000 to about 30,000, about 5,000 to about 25,000, about 5,000 to about 20,000, about 5,000 to about 15,000, about 5,000 to about 10,000, about 5,000 to about 7,500, about 7,500 to about 10,000,000, about 7,500 to about 9,000,000, about 7,500 to about 8,000,000, about 7,500 to about 7,000,000, about 7,500 to about 6,000,000, about 7,500 to about 5,000,000, about 7,500 to about 4,000,000, about 7,500 to about 3,000,000, about 7,500 to about 2,000,000, about 7,500 to about 1,000,000, about 7,500 to about 800,000, about 7,500 to about 600,000, about 7,500 to about 400,000, about 7,500 to about 200,000, about 7,500 to about 100,000, about 7,500 to about 80,000, about 7,500 to about 75,000, about 7,500 to about 70,000, about 7,500 to about 65,000, about 7,500 to about 60,000, about 7,500 to about 55,000, about 7,500 to About 50,000, about 7,500 to about 45,000, about 7,500 to about 40,000, about 7,500 to about 35,000, about 7,500 to about 30,000, about 7,500 to about 25,000, about 7,500 to about 20,000, about 7,500 to about 15,000, about 7,500 to about 10,000, about 10,000 to about 10,000,000, about 10,000 to about 9,000,000, about 10,000 to about 8,000,000, about 10,000 to about 7,000,000, about 10,000 to about 6,000,000 , about 10,000 to about 5,000,000, about 10,000 to about 4,000,000, about 10,000 to about 3,000,000, about 10,000 to about 2,000,000, about 10,000 to about 1,000,000, about 10,000 to about 800,000, about 10,000 to about 600,000, about 10,000 to about 400,000, about 10,000 to about 200,000, about 10,000 to about 100,000, about 10,000 to about 80,000, about 10,000 to about 75,000, about 10,000 to about 70, 000, about 10,000 to about 65,000, about 10,000 to about 60,000, about 10,000 to about 55,000, about 10,000 to about 50,000, about 10,000 to about 45,000, about 10,000 to about 40,000, about 10,000 to about 35,000, about 10,000 to about 30,000, about 10,000 to about 25,000, about 10,000 to about 20,000, about 10,000 to about 15,000, about 15,000 to about 10,000,000, about 15,000 to about 9,000,000,000 to about 8,000,000, about 15,000 to about 7,000,000, about 15,000 to about 6,000,000, about 15,000 to about 5,000,000, about 15,000 to about 4,000,000, about 15,000 to about 3,000,000, about 15,000 to about 2,000,000, about 15,000 to about 1,000,000, about 15,000 to about 800,000, about 15,000 to about 600,000, about 15,000 to about 400,000, about 15,000 to about 200,000, to about 100,000, about 15,000 to about 80,000, about 15,000 to about 75,000, about 15,000 to about 70,000, about 15,000 to about 65,000, about 15,000 to about 60,000, about 15,000 to about 55,000, about 15,000 to about 50,000, about 15,000 to about 45,000, about 15,000 to about 40,000, about 15,000 to about 35,000, about 15,000 to about 30,000, about 15,000 to about 25,000, about 15,000 to about 20,000, about 20 ,000 to about 10,000,000, about 20,000 to about 9,000,000, about 20,000 to about 8,000,000, about 20,000 to about 7,000,000, about 20,000 to about 6,000,000, about 20,000 to about 5,000,000, about 20,000 to about 4,000,000, about 20,000 to about 3,000,000, about 20,000 to about 2,000,000, about 20,000 to about 1,000,000, about 20,000 to about 800,000, about 20,000 to about 600,000, 0,000 to about 400,000, about 20,000 to about 200,000, about 20,000 to about 100,000, about 20,000 to about 80,000, about 20,000 to about 75,000, about 20,000 to about 70,000, about 20,000 to about 65,000, about 210,000 to about 60,000, about 20,000 to about 55,000, about 20,000 to about 50,000, about 20,000 to about 45,000, about 20,000 to about 40,000, about 20,000 to about 35,000, about 20,000 to about 30,000, about 20,000 to about 25,000, about 25,000 to about 10,000,000, about 25,000 to about 9,000,000, about 25,000 to about 8,000,000, about 25,000 to about 7,000,000, about 25,000 to about 6,000,000, about 25,000 to about 5,000,000, about 25,000 to about 4,000,000, about 25,000 to about 3,000,000, about 25,000 to about 2,000,000, about 25,000 to about 1,000,000, about 25,000 to about 800,000 00, about 25,000 to about 600,000, about 25,000 to about 400,000, about 25,000 to about 200,000, about 25,000 to about 100,000, about 25,000 to about 80,000, about 25,000 to about 75,000, about 25,000 to about 70,000, about 25,000 to about 65,000, about 25,000 to about 60,000, about 25,000 to about 55,000, about 25,000 to about 50,000, about 25,000 to about 45,000, about 25,000 to about 40,000, about 25,000 to about to about 35,000, about 25,000 to about 30,000, about 30,000 to about 10,000,000, about 30,000 to about 9,000,000, about 30,000 to about 8,000,000, about 30,000 to about 7,000,000, about 30,000 to about 6,000,000, about 30,000 to about 5,000,000, about 30,000 to about 4,000,000, about 30,000 to about 3,000,000, about 30,000 to about 2,000,000, about 30,000 to about 1,000,000, about 30,000 to about 8 00,000, about 30,000 to about 600,000, about 30,000 to about 400,000, about 30,000 to about 200,000, about 30,000 to about 100,000, about 30,000 to about 80,000, about 30,000 to about 75,000, about 30,000 to about 70,000, about 30,000 to about 65,000, about 30,000 to about 60,000, about 30,000 to about 55,000, about 30,000 to about 50,000, about 30,000 to about 45,000, about 30,000 to about 40,000, about 30,000 to about 35,000, about 35,000 to about 10,000,000, about 35,000 to about 9,000,000, about 35,000 to about 8,000,000, about 35,000 to about 7,000,000, about 35,000 to about 6,000,000, about 35,000 to about 5,000,000, about 35,000 to about 4,000,000, about 35,000 to about 3,000,000, about 35,000 to about 2,000,000, about 35,000 to about 1,000,000, about 35,000 to about 800,000, about 35,000 0 to about 600,000, about 35,000 to about 400,000, about 35,000 to about 200,000, about 35,000 to about 100,000, about 35,000 to about 80,000, about 35,000 to about 75,000, about 35,000 to about 70,000, about 35,000 to about 65,000, about 35,000 to about 60,000, about 35,000 to about 55,000, about 35,000 to about 50,000, about 35,000 to about 45,000, about 35,000 to about 40,000, about 40,000 to about 10,000, 00, about 40,000 to about 9,000,000, about 40,000 to about 8,000,000, about 40,000 to about 7,000,000, about 40,000 to about 6,000,000, about 40,000 to about 5,000,000, about 40,000 to about 4,000,000, about 40,000 to about 3,000,000, about 40,000 to about 2,000,000, about 40,000 to about 1,000,000, about 40,000 to about 800,000, about 40,000 to about 600,000, about 40,000 to about 400,000, About 40,000 to about 200,000, about 40,000 to about 100,000, about 40,000 to about 80,000, about 40,000 to about 75,000, about 40,000 to about 70,000, about 40,000 to about 65,000, about 40,000 to about 60,000, about 40,000 to about 55,000, about 40,000 to about 50,000, about 40,000 to about 45,000, about 45,000 to about 10,000,000, about 45,000 to about 9,000,000, about 45,000 to about 8,000,000, about 45,000 to about 7,000,000, about 45,000 to about 6,000,000, about 45,000 to about 5,000,000, about 45,000 to about 4,000,000, about 45,000 to about 3,000,000, about 45,000 to about 2,000,000, about 45,000, to about 1,000,000, about 45,000 to about 800,000, about 45,000 to about 600,000, about 45,000 to about 400,000, about 45,000 to about 200,000, about 45,000 to about 100,000, about 45,000 to about 80,000, about 45,000 to about 75,000, about 45,000 to about 70,000, about 45,000 to about 65,000, about 45,000 to about 60,000, about 45,000 to about 55,000, about 45,000 to about 50,000, about 50,000 to about 10, 000,000, about 50,000 to about 9,000,000, about 50,000 to about 8,000,000, about 50,000 to about 7,000,000, about 50,000 to about 6,000,000, about 50,000 to about 5,000,000, about 50,000 to about 4,000,000, about 50,000 to about 3,000,000, about 50,000 to about 2,000,000, about 50,000 to about 1,000,000, about 50,000 to about 800,000, about 50,000 to about 600,000, about 50,000 to about 400 ,000, about 50,000 to about 200,000, about 50,000 to about 100,000, about 50,000 to about 80,000, about 50,000 to about 75,000, about 50,000 to about 70,000, about 50,000 to about 65,000, about 50,000 to about 60,000, about 50,000 to about 55,000, about 55,000 to about 10,000,000, about 55,000 to about 9,000,000, about 55,000 to about 8,000,000, about 55,000 to about 7,000,000, about 55,000 to about 6, 000,000, about 55,000 to about 5,000,000, about 55,000 to about 4,000,000, about 55,000 to about 3,000,000, about 55,000 to about 2,000,000, about 55,000 to about 1,000,000, about 55,000 to about 800,000, about 55,000 to about 600,000, about 55,000 to about 400,000, about 55,000 to about 200,000, about 55,000 to about 100,000, about 55,000 to about 80,000, about 55,000 to about 75,000, about 55,000 to about 70,000, about 55,000 to about 65,000, about 55,000 to about 60,000, about 60,000 to about 10,000,000, about 60,000 to about 9,000,000, about 60,000 to about 8,000,000, about 60,000 to about 7,000,000, about 60,000 to about 6,000,000, about 60,000 to about 5,000,000, about 60,000 to about 4,000,000, about 60,000 to about 3,000,000, about 60,000 to about 2,000,000, to about 1,000,000, about 60,000 to about 800,000, about 60,000 to about 600,000, about 60,000 to about 400,000, about 60,000 to about 200,000, about 60,000 to about 100,000, about 60,000 to about 80,000, about 60,000 to about 75,000, about 60,000 to about 70,000, about 60,000 to about 65,000, about 65,000 to about 10,000,000, about 65,000 to about 9,000,000, about 65,000 to about 8,000,000, 00 to about 7,000,000, about 65,000 to about 6,000,000, about 65,000 to about 5,000,000, about 65,000 to about 4,000,000, about 65,000 to about 3,000,000, about 65,000 to about 2,000,000, about 65,000 to about 1,000,000, about 65,000 to about 800,000, about 65,000 to about 600,000, about 65,000 to about 400,000, about 65,000 to about 200,000, about 65,000 to about 100,000, about 65,000 to about 8 0,000, about 65,000 to about 75,000, about 65,000 to about 70,000, about 70,000 to about 10,000,000, about 70,000 to about 9,000,000, about 70,000 to about 8,000,000, about 70,000 to about 7,000,000, about 70,000 to about 6,000,000, about 70,000 to about 5,000,000, about 70,000 to about 4,000,000, about 70,000 to about 3,000,000, about 70,000 to about 2,000,000, about 70,000 to about 1,000,000, about 70,000 to about 800,000, about 70,000 to about 600,000, about 70,000 to about 400,000, about 70,000 to about 200,000, about 70,000 to about 100,000, about 70,000 to about 90,000, about 70,000 to about 80,000, about 80,000 to about 10,000,000, about 80,000 to about 9,000,000, about 80,000 to about 8,000,000, about 80,000 to about 7,000,000, about 80,000 to about 6,000,000, about 80,000 0 to about 5,000,000, about 80,000 to about 4,000,000, about 80,000 to about 3,000,000, about 80,000 to about 2,000,000, about 80,000 to about 1,000,000, about 80,000 to about 800,000, about 80,000 to about 600,000, about 80,000 to about 400,000, about 80,000 to about 200,000, about 80,000 to about 100,000, about 80,000 to about 90,000, about 90,000 to about 10,000,000, about 90,000 to about 9,000 0,000, about 90,000 to about 8,000,000, about 90,000 to about 7,000,000, about 90,000 to about 6,000,000, about 90,000 to about 5,000,000, about 90,000 to about 4,000,000, about 90,000 to about 3,000,000, about 90,000 to about 2,000,000, about 90,000 to about 1,000,000, about 90,000 to about 800,000, about 90,000 to about 600,000, about 90,000 to about 400,000, about 90,000 to about 200,000 0, about 90,000 to about 100,000, about 100,000 to about 10,000,000, about 100,000 to about 9,000,000, about 100,000 to about 8,000,000, about 100,000 to about 7,000,000, about 100,000 to about 6,000,000, about 100,000 to about 5,000,000, about 100,000 to about 4,000,000, about 100,000 to about 3,000,000, about 100,000 to about 2,000,000, about 100,000 to about 1,000,000, about 100,000 to about 800,000, about 100,000 to about 600,000, about 100,000 to about 400,000, about 100,000 to about 200,000, about 200,000 to about 10,000,000, about 200,000 to about 9,000,000, about 200,000 to about 8,000,000, about 200,000 to about 7,000,000, about 200,000 to about 6,000,000, about 200,000 to about 5,000,000, about 200,000 to about 4,000,000, about 200,000 to about 3,000,000 0, about 200,000 to about 2,000,000, about 200,000 to about 1,000,000, about 200,000 to about 800,000, about 200,000 to about 600,000, about 200,000 to about 400,000, about 400,000 to about 10,000,000, about 400,000 to about 9,000,000, about 400,000 to about 8,000,000, about 400,000 to about 7,000,000, about 400,000 to about 6,000,000, about 400,000 to about 5,000,000, about 400,000 to about to about 4,000,000, about 400,000 to about 3,000,000, about 400,000 to about 2,000,000, about 400,000 to about 1,000,000, about 400,000 to about 800,000, about 400,000 to about 600,000, about 600,000 to about 10,000,000, about 600,000 to about 9,000,000, about 600,000 to about 8,000,000, about 600,000 to about 7,000,000, about 600,000 to about 6,000,000, about 600,000 to about 5,000,000 0, about 600,000 to about 4,000,000, about 600,000 to about 3,000,000, about 600,000 to about 2,000,000, about 600,000 to about 1,000,000, about 600,000 to about 800,000, about 800,000 to about 10,000,000, about 800,000 to about 9,000,000, about 800,000 to about 8,000,000, about 800,000 to about 7,000,000, about 800,000 to about 6,000,000, about 800,000 to about 5,000,000, about 800,000 to about 4,000,000, about 800,000 to about 3,000,000, about 800,000 to about 2,000,000, about 800,000 to about 1,000,000, about 1,000,000 to about 10,000,000, about 1,000,000 to about 9,000,000, about 1,000,000 to about 8,000,000, about 1,000,000 to about 7,000,000, about 1,000,000 to about 6,000,000, about 1,000,000 to about 5,000,000, about 1,000,000 to about 4,000,000 0, about 1,000,000 to about 3,000,000, about 1,000,000 to about 2,000,000, about 2,000,000 to about 10,000,000, about 2,000,000 to about 9,000,000, about 2,000,000 to about 8,000,000, about 2,000,000 to about 7,000,000, about 2,000,000 to about 6,000,000, about 2,000,000 to about 5,000,000, about 2,000,000 to about 4,000,000, about 2,000,000 to about 3,000,000, about 3,000 0,000 to about 10,000,000, about 3,000,000 to about 9,000,000, about 3,000,000 to about 8,000,000, about 3,000,000 to about 7,000,000, about 3,000,000 to about 6,000,000, about 3,000,000 to about 5,000,000, about 3,000,000 to about 4,000,000, about 4,000,000 to about 10,000,000, about 4,000,000 to about 9,000,000, about 4,000,000 to about 8,000,000, About 7,000,000, about 4,000,000 to about 6,000,000, about 4,000,000 to about 5,000,000, about 5,000,000 to about 10,000,000, about 5,000,000 to about 9,000,000, about 5,000,000 to about 8,000,000, about 5,000,000 to about 7,000,000, about 5,000,000 to about 6,000,000, about 6,000,000 to about 10,000,000, about 6,000,000 to about 9,000,000, about 6,000,000 to about 8,000,000, about 6,000,000 to about 7,000,000, about 7,000,000 to about 10,000,000, about 7,000,000 to about 9,000,000, about 7,000,000 to about 8,000,000, about 8,000,000 to about 10,000,000, about 8,000,000 to about 9,000,000 The METs may be 0, or from about 9,000,000 to about 10,000,000.

[0066] The phrase "antigen density" refers to the number of METs present on the surface of a target mammalian cell, or the average number of METs on the surface of a population of target mammalian cells of a particular type, which can be measured, for example, using a Quantibright bead kit or radiolabeling (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, Catalog No. 340495).

[0067] The phrase "amino acid substituted with histidine" refers to the substitution of a non-histidine amino acid residue in a reference polypeptide sequence with histidine. Non-limiting methods for substituting an amino acid residue in a reference polypeptide with histidine are described herein. Additional methods for substituting an amino acid residue in a reference polypeptide with histidine are known in the art.

[0068] The phrase "amino acid substituted with alanine" refers to the substitution of an amino acid residue that is a histidine in a reference polypeptide sequence with alanine. Non-limiting methods for substituting alanine for histidine in a reference polypeptide are described herein. Additional methods for substituting alanine for a histidine in a reference polypeptide are known in the art.

[0069] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials for use in the present invention are described herein; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

[0070] Other features and advantages of the invention will become apparent from the following detailed description and figures, and from the claims. In certain embodiments, for example, the following are provided: (Item 1) 1. A pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D 10. A pharmaceutical composition comprising said effective amount of an antigen binding protein construct (ABPC), wherein said effective amount is greater than or equal to: (Item 2) 2. The pharmaceutical composition according to item 1, wherein the ABPC is degraded in the target mammalian cells after internalization of the ABPC by the target mammalian cells. (Item 3) 3. The pharmaceutical composition of item 1 or 2, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. (Item 4) 1. A pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; and Conjugated toxins, radioisotopes, drugs, or small molecules, (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or The dissociation constant (K D ) at pH 7.0 to 8.0 D Larger and (b) the composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; increased killing of target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and a pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), wherein the pharmaceutical composition provides one or more of the following: increased endolysosomal delivery in the target mammalian cell compared to a composition comprising an equivalent amount of a control ABPC. (Item 5) 5. The pharmaceutical composition of item 1 or 4, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain of telisotuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 1; and / or a light chain variable domain of telisotuzumab comprising SEQ ID NO: 2, wherein one or more amino acids are substituted with histidine; (b) a heavy chain variable domain of emibetuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 146; and / or a light chain variable domain of emibetuzumab comprising SEQ ID NO: 147, wherein one or more amino acids are substituted with histidine; (c) a heavy chain variable domain of hucMET27Gv1.3 in which one or more amino acids are substituted with histidine, said heavy chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 304; and / or a light chain variable domain of hucMET27Gv1.3, wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 305; and (d) a heavy chain variable domain of P3D12 in which one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 502; and / or A light chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 503. (Item 6) 5. The pharmaceutical composition according to item 1 or 4, wherein the first MET-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 3 to 5, wherein one or more amino acid positions in total in SEQ ID NOs: 3 to 5 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 6 to 8, wherein a total of one or more amino acid positions in SEQ ID NOs: 6 to 8 are substituted with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 148 to 150, wherein one or more amino acid positions in total in SEQ ID NOs: 148 to 150 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each represented by SEQ ID NOs: 151 to 153, wherein one or more amino acid positions in total in SEQ ID NOs: 151 to 153 are substituted with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 306 to 308, wherein the CDR1, CDR2, and CDR3 are collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 306 to 308; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 309 to 311, wherein a total of one or more amino acid positions in SEQ ID NOs: 309 to 311 are substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 504 to 506, wherein one or more amino acid positions in total in SEQ ID NOs: 504 to 506 are substituted with histidine; and / or A light chain variable domain comprising CDR1, CDR2 and CDR3, each of which is represented by SEQ ID NOs: 507 to 509, wherein a total of one or more amino acid positions in SEQ ID NOs: 507 to 509 have been substituted with histidine. (Item 7) 7. The pharmaceutical composition according to any one of items 1 and 4 to 6, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107; and / or a light chain variable domain at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101; (b) a heavy chain variable domain at least 90% identical to SEQ ID NO: 146, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 147, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97; (c) a heavy chain variable domain at least 90% identical to SEQ ID NO: 304, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 304 selected from the group consisting of 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 105; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 305, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101; and (d) a heavy chain variable domain at least 90% identical to SEQ ID NO: 502, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 502 selected from the group consisting of 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101, 102, 103, 106, and 107; and / or A light chain variable domain at least 90% identical to SEQ ID NO: 503, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 503 selected from the group consisting of 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98. (Item 8) 5. The pharmaceutical composition of item 1 or 4, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a light chain variable domain of SEQ ID NO:2, SEQ ID NO:52, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, or SEQ ID NO:140; and / or a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:94, or SEQ ID NO:111; the light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain of SEQ ID NO: 1, (ii) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain that is not one of SEQ ID NOs: 13 to 16, 19, 40 to 46, 50, 82 to 84, 86, 87, 89, 90, 94, and 111, or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; (b) a light chain variable domain of SEQ ID NO:147, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:194, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:300, or SEQ ID NO:301; and / or a heavy chain variable domain of SEQ ID NO:146, SEQ ID NO:159, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:187, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, or SEQ ID NO:236; the light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain of SEQ ID NO: 146, (ii) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164 to 168, 170, 171, 173, 182 to 184, 187, 217 to 228, and 230 to 236, or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 146 and a light chain variable domain that is not one of SEQ ID NOs: 190, 191, 194, 197, 198, 200, 201, 209, 210, 213 to 215, 284 to 298, 300, and 301; (c) SEQ ID NO: 305, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 360, SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 365, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 374, SEQ ID NO: 378, SEQ ID NO: 380, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430, SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436, SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, 441, SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:450, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:457, SEQ ID NO:462, SEQ ID NO:463, SEQ ID NO:465, SEQ ID NO:470, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:476, SEQ ID NO:479, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:485, SEQ ID NO:490, SEQ ID NO:492, SEQ ID NO:494, SEQ ID NO:496, or SEQ ID NO:499; and / or a heavy chain variable domain of SEQ ID NO:304, SEQ ID NO:313, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:345, SEQ ID NO:347, SEQ ID NO:381, SEQ ID NO:382, SEQ ID NO:383, SEQ ID NO:384, SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389, SEQ ID NO:390, SEQ ID NO:392, SEQ ID NO:393, SEQ ID NO:395, SEQ ID NO:396, SEQ ID NO:397, SEQ ID NO:398, SEQ ID NO:399, or SEQ ID NO:400; The first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 304; (ii) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain that is not one of SEQ ID NOs: 313, 320 to 324, 326 to 337, 340, 341, 345, 347, 381 to 390, 392, 393, and 395 to 400; or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 304 and a heavy chain variable domain of SEQ ID NO: 352, the light chain variable domain and / or the heavy chain variable domain does not include a light chain variable domain that is not one of 356, 357, 360, 362, 364, 365, 367, 368, 371, 372, 374, 378, 380, 428 to 446, 450, 451, 453, 457, 462, 463, 465, 470, 472 to 474, 476, 479, 482, 483, 485, 490, 492, 494, 496, and 499; and (d) a light chain variable domain of SEQ ID NO:503, SEQ ID NO:550, SEQ ID NO:554, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:562, SEQ ID NO:565, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ ID NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, or SEQ ID NO:732; and / or a heavy chain variable domain of SEQ ID NO:502, SEQ ID NO:511, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, SEQ ID NO:522, SEQ ID NO:523, SEQ ID NO:527, SEQ ID NO:529, SEQ ID NO:538, SEQ ID NO:540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:546, SEQ ID NO:547, SEQ ID NO:578, SEQ ID NO:579, SEQ ID NO:580, SEQ ID NO:581, SEQ ID NO:582, SEQ ID NO:583, SEQ ID NO:584, SEQ ID NO:585, SEQ ID NO:586, SEQ ID NO:587, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:590, SEQ ID NO:591, SEQ ID NO:592, SEQ ID NO:593, SEQ ID NO:594, SEQ ID NO:595, SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:606, SEQ ID NO:621, SEQ ID NO:659 or SEQ ID NO:676; The light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise the light chain variable domain of SEQ ID NO: 503 and the heavy chain variable domain of SEQ ID NO: 502, or (ii) does not comprise the light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain that is not one of SEQ ID NOs: 511, 513, 514, 516 to 523, 527, 529, 538, 540 to 543, 546, 547, 578 to 597, 606, 621, 659, and 676, or (iii) does not comprise the heavy chain variable domain of SEQ ID NO: 502 and a light chain variable domain that is not one of SEQ ID NOs: 550, 554, 556 to 560, 562, 565, 569, 570 to 576, 697 to 713, and 732. (Item 9) The composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and / or 9. The pharmaceutical composition of any one of items 1 to 8, which provides increased killing of target mammalian cells compared to a composition containing the same amount of control ABPC. (Item 10) 10. The pharmaceutical composition according to any one of items 1 to 9, wherein the composition provides increased endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of control ABPC. (Item 11) The composition comprises: does not cause a significant decrease in the level of MET present on the surface of said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; or 11. The pharmaceutical composition according to any one of items 1 to 10, which does not result in a detectable decrease in the level of MET present on the surface of said target mammalian cells. (Item 12) 12. The pharmaceutical composition according to any one of items 1 to 11, wherein the target mammalian cells are cancer cells. (Item 13) 13. The pharmaceutical composition according to any one of items 1 to 12, wherein said ABPC is cytotoxic or cytostatic to said target mammalian cells. (Item 14) The ABPC is is cross-reactive with non-human primate MET and human MET, or 14. The pharmaceutical composition according to any one of items 1 to 13, which is cross-reactive with non-human primate MET, human MET, and one or both of rat MET and mouse MET. (Item 15) 15. The pharmaceutical composition according to any one of items 1 to 14, wherein the ABPC comprises a single polypeptide. (Item 16) 16. The pharmaceutical composition of item 15, wherein the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. (Item 17) 15. The pharmaceutical composition according to any one of items 1 to 14, wherein the ABPC comprises two or more polypeptides. (Item 18) 18. The pharmaceutical composition of item 17, wherein the ABPC is an antibody. (Item 19) 19. The pharmaceutical composition of any one of items 1 to 18, wherein the half-life of the ABPC in vivo is reduced compared to the half-life of a control ABPC in vivo. (Item 20) 20. The pharmaceutical composition according to any one of items 1 to 19, wherein the ABPC further comprises a second antigen-binding domain. (Item 21) An antigen binding protein construct (ABPC), comprising: a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D Antigen binding protein constructs (ABPCs), which are larger than (Item 22) 22. The ABPC according to item 21, wherein the ABPC is degraded in the target mammalian cells after internalization of the ABPC by the target mammalian cells. (Item 23) 23. The ABPC of item 21 or 22, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule. (Item 24) An antigen binding protein construct (ABPC), comprising: a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; and Conjugated toxins, radioisotopes, drugs, or small molecules, (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, or The dissociation constant (K D ) at pH 7.0 to 8.0D Larger and (b) the composition comprises: an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; increased killing of target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and and increased endolysosomal delivery in said target mammalian cells compared to a composition comprising an equivalent amount of control ABPC. (Item 25) 25. The ABPC of item 21 or 24, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain of telisotuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 1; and / or a light chain variable domain of telisotuzumab comprising SEQ ID NO: 2, wherein one or more amino acids are substituted with histidine; (b) a heavy chain variable domain of emibetuzumab, wherein one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 146; and / or a light chain variable domain of emibetuzumab comprising SEQ ID NO: 147, wherein one or more amino acids are substituted with histidine; (c) a heavy chain variable domain of hucMET27Gv1.3 in which one or more amino acids are substituted with histidine, said heavy chain variable domain of hucMET27Gv1.3 comprising SEQ ID NO: 304; and / or a light chain variable domain of hucMET27Gv1.3, wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 305; and (d) a heavy chain variable domain of P3D12 in which one or more amino acids are substituted with histidine, said heavy chain variable domain comprising SEQ ID NO: 502; and / or A light chain variable domain of P3D12 wherein one or more amino acids are substituted with histidine, said light chain variable domain comprising SEQ ID NO: 503. (Item 26) 25. The ABPC according to item 21 or 24, wherein the first MET-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 3 to 5, wherein one or more amino acid positions in total in SEQ ID NOs: 3 to 5 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 6 to 8, wherein a total of one or more amino acid positions in SEQ ID NOs: 6 to 8 are substituted with histidine; (b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 148 to 150, wherein one or more amino acid positions in total in SEQ ID NOs: 148 to 150 are substituted with histidine; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each represented by SEQ ID NOs: 151 to 153, wherein one or more amino acid positions in total in SEQ ID NOs: 151 to 153 are substituted with histidine; (c) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 306 to 308, wherein the CDR1, CDR2, and CDR3 are collectively substituted with histidine at one or more amino acid positions in SEQ ID NOs: 306 to 308; and / or a light chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 309 to 311, wherein a total of one or more amino acid positions in SEQ ID NOs: 309 to 311 are substituted with histidine; and (d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3, each of which is represented by SEQ ID NOs: 504 to 506, wherein one or more amino acid positions in total in SEQ ID NOs: 504 to 506 are substituted with histidine; and / or A light chain variable domain comprising CDR1, CDR2 and CDR3, each of which is represented by SEQ ID NOs: 507 to 509, wherein a total of one or more amino acid positions in SEQ ID NOs: 507 to 509 have been substituted with histidine. (Item 27) 27. The ABPC of any one of items 21 and 24 to 26, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a heavy chain variable domain at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107; and / or a light chain variable domain at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101; (b) a heavy chain variable domain at least 90% identical to SEQ ID NO: 146, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 147, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97; (c) a heavy chain variable domain at least 90% identical to SEQ ID NO: 304, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 304 selected from the group consisting of 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 105; and / or a light chain variable domain at least 90% identical to SEQ ID NO: 305, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101; and (d) a heavy chain variable domain at least 90% identical to SEQ ID NO: 502, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 502 selected from the group consisting of 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101, 102, 103, 106, and 107; and / or A light chain variable domain at least 90% identical to SEQ ID NO: 503, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 503 selected from the group consisting of 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98. (Item 28) 25. The ABPC of item 21 or 24, wherein the first antigen-binding domain comprises one of the following (a) to (d): (a) a light chain variable domain of SEQ ID NO:2, SEQ ID NO:52, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, or SEQ ID NO:140; and / or a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:94, or SEQ ID NO:111; the light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain of SEQ ID NO: 1, (ii) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain that is not one of SEQ ID NOs: 13 to 16, 19, 40 to 46, 50, 82 to 84, 86, 87, 89, 90, 94, and 111, or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not one of SEQ ID NOs: 52, 55 to 59, 61 to 67, 71, 72, 75, 79, 81, and 131 to 140; (b) a light chain variable domain of SEQ ID NO:147, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:194, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:300, or SEQ ID NO:301; and / or a heavy chain variable domain of SEQ ID NO:146, SEQ ID NO:159, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:187, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, or SEQ ID NO:236; the light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain of SEQ ID NO: 146, (ii) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164 to 168, 170, 171, 173, 182 to 184, 187, 217 to 228, and 230 to 236, or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 146 and a light chain variable domain that is not one of SEQ ID NOs: 190, 191, 194, 197, 198, 200, 201, 209, 210, 213 to 215, 284 to 298, 300, and 301; (c) SEQ ID NO: 305, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 360, SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 365, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 374, SEQ ID NO: 378, SEQ ID NO: 380, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430, SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436, SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, 441, SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:450, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:457, SEQ ID NO:462, SEQ ID NO:463, SEQ ID NO:465, SEQ ID NO:470, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:476, SEQ ID NO:479, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:485, SEQ ID NO:490, SEQ ID NO:492, SEQ ID NO:494, SEQ ID NO:496, or SEQ ID NO:499; and / or a heavy chain variable domain of SEQ ID NO:304, SEQ ID NO:313, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:345, SEQ ID NO:347, SEQ ID NO:381, SEQ ID NO:382, SEQ ID NO:383, SEQ ID NO:384, SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389, SEQ ID NO:390, SEQ ID NO:392, SEQ ID NO:393, SEQ ID NO:395, SEQ ID NO:396, SEQ ID NO:397, SEQ ID NO:398, SEQ ID NO:399, or SEQ ID NO:400; The first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 304; (ii) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain that is not one of SEQ ID NOs: 313, 320 to 324, 326 to 337, 340, 341, 345, 347, 381 to 390, 392, 393, and 395 to 400; or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 304 and a heavy chain variable domain of SEQ ID NO: 352, the light chain variable domain and / or the heavy chain variable domain does not include a light chain variable domain that is not one of 356, 357, 360, 362, 364, 365, 367, 368, 371, 372, 374, 378, 380, 428 to 446, 450, 451, 453, 457, 462, 463, 465, 470, 472 to 474, 476, 479, 482, 483, 485, 490, 492, 494, 496, and 499; and (d) a light chain variable domain of SEQ ID NO:503, SEQ ID NO:550, SEQ ID NO:554, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:562, SEQ ID NO:565, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ ID NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, or SEQ ID NO:732; and / or a heavy chain variable domain of SEQ ID NO:502, SEQ ID NO:511, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, SEQ ID NO:522, SEQ ID NO:523, SEQ ID NO:527, SEQ ID NO:529, SEQ ID NO:538, SEQ ID NO:540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:546, SEQ ID NO:547, SEQ ID NO:578, SEQ ID NO:579, SEQ ID NO:580, SEQ ID NO:581, SEQ ID NO:582, SEQ ID NO:583, SEQ ID NO:584, SEQ ID NO:585, SEQ ID NO:586, SEQ ID NO:587, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:590, SEQ ID NO:591, SEQ ID NO:592, SEQ ID NO:593, SEQ ID NO:594, SEQ ID NO:595, SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:606, SEQ ID NO:621, SEQ ID NO:659 or SEQ ID NO:676; The light chain variable domain and / or the heavy chain variable domain, wherein the first antigen-binding domain (i) does not comprise the light chain variable domain of SEQ ID NO: 503 and the heavy chain variable domain of SEQ ID NO: 502, or (ii) does not comprise the light chain variable domain of SEQ ID NO: 503 and a heavy chain variable domain that is not one of SEQ ID NOs: 511, 513, 514, 516 to 523, 527, 529, 538, 540 to 543, 546, 547, 578 to 597, 606, 621, 659, and 676, or (iii) does not comprise the heavy chain variable domain of SEQ ID NO: 502 and a light chain variable domain that is not one of SEQ ID NOs: 550, 554, 556 to 560, 562, 565, 569, 570 to 576, 697 to 713, and 732. (Item 29) The composition comprising ABPC is an increase in toxin release in said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; and / or 29. The ABPC of any one of items 21 to 28, which provides increased killing of target mammalian cells compared to a composition comprising an equivalent amount of control ABPC. (Item 30) 30. The ABPC according to any one of items 21 to 29, wherein a composition comprising the ABPC provides increased endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of control ABPC. (Item 31) The composition comprising ABPC is does not cause a significant decrease in the level of MET present on the surface of said target mammalian cells compared to a composition containing an equivalent amount of control ABPC; or 31. The ABPC of any one of items 21 to 30, which does not result in a detectable decrease in the level of MET present on the surface of said target mammalian cells. (Item 32) 32. The ABPC according to any one of items 21 to 31, wherein the target mammalian cells are cancer cells. (Item 33) 33. The ABPC according to any one of items 21 to 32, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cells. (Item 34) The ABPC is is cross-reactive with non-human primate MET and human MET, or 34. The ABPC of any one of items 21 to 33, which is cross-reactive with non-human primate MET, human MET, and one or both of rat MET and mouse MET. (Item 35) 35. The ABPC according to any one of items 21 to 34, wherein the ABPC comprises a single polypeptide. (Item 36) 36. The ABPC of item 35, wherein the antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv. (Item 37) 35. The ABPC according to any one of items 21 to 34, wherein the ABPC comprises two or more polypeptides. (Item 38) 38. The ABPC of item 37, wherein the ABPC is an antibody. (Item 39) 39. The ABPC of any one of items 21 to 38, wherein the half-life of said ABPC in vivo is decreased compared to the half-life of a control ABPC in vivo. (Item 40) 40. The ABPC according to any one of items 21 to 39, wherein the ABPC further comprises a second antigen-binding domain. (Item 41) A kit comprising at least one dose of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40. (Item 42) 1. A method of treating a cancer characterized by having a population of cancer cells having MET or an epitope of MET present on the surface of the cancer cells, comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 43) 1. A method of reducing tumor volume in a subject, wherein the tumor is characterized by having a population of cancer cells that have MET or an epitope of MET present on their surface, the method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 44) 1. A method for inducing cell death of cancer cells in a subject, the cancer cells having MET or an epitope of MET present on their surface, the method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. (Item 45) 1. A method of reducing the risk of developing metastases or reducing the risk of developing further metastases in a subject having cancer, wherein the cancer is characterized by having a population of cancer cells that have MET or an epitope of MET present on their surface, the method comprising: A method comprising administering a therapeutically effective amount of the pharmaceutical composition according to any one of items 1 to 20 or the ABPC according to any one of items 21 to 40 to a subject identified as having a cancer characterized by having the population of cancer cells. [Brief explanation of the drawings]

[0071] [Figure 1] Figure 1 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of telisotuzumab and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT0886 represents telisotuzumab, and the remaining lanes (MYT0887-MYT0924) represent histidine-scanning and alanine-scanning mutants of the heavy chain of telisotuzumab. [Figure 2-1] Figures 2a-2am show the binding of telisotuzumab-starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the heavy chain, MYT0886 (telisotuzumab) and MYT0887-MYT0924, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 2-2] Same as above. [Figure 2-3] Same as above. [Figure 2-4] Same as above. [Figure 2-5] Same as above. [Figure 2-6]Same as above. [Figure 2-7] Same as above. [Figure 2-8] Same as above. [Figure 2-9] Same as above. [Figure 2-10] Same as above. [Figure 2-11] Same as above. [Figure 2-12] Same as above. [Figure 2-13] Same as above. [Figure 2-14] Same as above. [Figure 2-15] Same as above. [Figure 2-16] Same as above. [Figure 2-17] Same as above. [Figure 2-18] Same as above. [Figure 2-19] Same as above. [Figure 2-20] Same as above. [Figure 2-21] Same as above. [Figure 2-22] Same as above. [Figure 2-23] Same as above. [Figure 2-24] Same as above. [Figure 2-25] Same as above. [Figure 2-26] Same as above. [Figure 2-27] Same as above. [Figure 2-28] Same as above. [Figure 2-29] Same as above. [Figure 2-30] Same as above. [Figure 2-31] Same as above. [Figure 2-32] Same as above. [Figure 2-33] Same as above. [Figure 2-34] Same as above. [Figure 2-35] Same as above. [Figure 2-36] Same as above. [Figure 2-37] Same as above. [Figure 2-38] Same as above. [Figure 2-39] Same as above. [Figure 3]Figure 3 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of telisotuzumab and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT0886 represents telisotuzumab, and the remaining lanes (MYT2028-MYT2058) represent histidine-scanning and alanine-scanning mutants of the light chain of telisotuzumab. [Figure 4-1] Figures 4a-4af show binding of telisotuzumab-starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. MYT0886 (telisotuzumab) and MYT2028-MYT2058 light chain histidine-scanning and alanine-scanning mutants were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 4-2] Same as above. [Figure 4-3] Same as above. [Figure 4-4] Same as above. [Figure 4-5] Same as above. [Figure 4-6] Same as above. [Figure 4-7] Same as above. [Figure 4-8] Same as above. [Figure 4-9] Same as above. [Figure 4-10] Same as above. [Figure 4-11] Same as above. [Figure 4-12] Same as above. [Figure 4-13] Same as above. [Figure 4-14] Same as above. [Figure 4-15] Same as above. [Figure 4-16] Same as above. [Figure 4-17] Same as above. [Figure 4-18] Same as above. [Figure 4-19] Same as above. [Figure 4-20] Same as above. [Figure 4-21] Same as above. [Figure 4-22] Same as above. [Figure 4-23] Same as above. [Figure 4-24] Same as above. [Figure 4-25] Same as above. [Figure 4-26] Same as above. [Figure 4-27] Same as above. [Figure 4-28] Same as above. [Figure 4-29] Same as above. [Figure 4-30] Same as above. [Figure 4-31] Same as above. [Figure 4-32] Same as above. [Figure 5] Figure 5 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of telisotuzumab. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT2018 to MYT2027 are histidine-scanning and alanine-scanning variants of the telisotuzumab heavy chain combination. [Figure 6a] Figures 6a-6j show the binding of histidine-scanning and alanine-scanning mutants of telisotuzumab to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of heavy chain combinations MYT2018-MYT2027 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 6b] Same as above. [Figure 6c] Same as above. [Figure 6d] Same as above. [Figure 6e] Same as above. [Figure 6f] Same as above. [Figure 6g] Same as above. [Figure 6h] Same as above. [Figure 6i] Same as above. [Figure 6j] Same as above. [Figure 7] Figure 7 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of telisotuzumab. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT4201 to MYT4210 are histidine-scanning and alanine-scanning variants of the telisotuzumab light chain combination. [Figure 8a] Figures 8a-8j show the binding of histidine-scanning and alanine-scanning mutants of telisotuzumab to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain combinations MYT4201-MYT4210 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 8b] Same as above. [Figure 8c] Same as above. [Figure 8d] Same as above. [Figure 8e] Same as above. [Figure 8f] Same as above. [Figure 8g] Same as above. [Figure 8h] Same as above. [Figure 8i] Same as above. [Figure 8j] Same as above. [Figure 9]Figure 9 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of telisotuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3451-MYT3492, MYT3603-MYT3616 and MYT4211-MYT4220 are paired heavy and light chain histidine scanning and alanine scanning mutants of telisotuzumab, which combine light chain histidine and alanine scanning mutants or combined light chain histidine scanning and alanine scanning mutants with heavy chain histidine and alanine scanning mutants or combined heavy chain histidine scanning and alanine scanning mutants. [Figure 10-1] 10a-10bn show the binding of histidine-scanning and alanine-scanning mutants of telisotuzumab to MET by biolayer interferometry. Paired heavy and light chain histidine-scanning and alanine-scanning mutants, MYT3451-MYT3492, MYT3603-MYT3616, and MYT4211-MYT4220, in combination with light chain histidine-scanning and alanine-scanning mutants or light chain combinations with heavy chain histidine-scanning and alanine-scanning mutants or heavy chain combinations, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 10-2] Same as above. [Figure 10-3] Same as above. [Figure 10-4] Same as above. [Figure 10-5] Same as above. [Figure 10-6] Same as above. [Figure 10-7] Same as above. [Figure 10-8] Same as above. [Figure 10-9] Same as above. [Figure 10-10] Same as above. [Figure 10-11] Same as above. [Figure 10-12] Same as above. [Figure 10-13] Same as above. [Figure 10-14] Same as above. [Figure 10-15] Same as above. [Figure 10-16] Same as above. [Figure 10-17] Same as above. [Figure 10-18] Same as above. [Figure 10-19] Same as above. [Figure 10-20] Same as above. [Figure 10-21] Same as above. [Figure 10-22] Same as above. [Figure 10-23] Same as above. [Figure 10-24] Same as above. [Figure 10-25] Same as above. [Figure 10-26] Same as above. [Figure 10-27] Same as above. [Figure 10-28] Same as above. [Figure 10-29] Same as above. [Figure 10-30] Same as above. [Figure 10-31] Same as above. [Figure 10-32] Same as above. [Figure 10-33] Same as above. [Figure 10-34] Same as above. [Figure 10-35] Same as above. [Figure 10-36] Same as above. [Figure 10-37] Same as above. [Figure 10-38] Same as above. [Figure 10-39] Same as above. [Figure 10-40] Same as above. [Figure 10-41] Same as above. [Figure 10-42] Same as above. [Figure 10-43] Same as above. [Figure 10-44] Same as above. [Figure 10-45] Same as above. [Figure 10-46] Same as above. [Figure 10-47] Same as above. [Figure 10-48] Same as above. [Figure 10-49] Same as above. [Figure 10-50] Same as above. [Figure 10-51] Same as above. [Figure 10-52] Same as above. [Figure 10-53] Same as above. [Figure 10-54] Same as above. [Figure 10-55] Same as above. [Figure 10-56] Same as above. [Figure 10-57] Same as above. [Figure 10-58] Same as above. [Figure 10-59] Same as above. [Figure 10-60] Same as above. [Figure 10-61] Same as above. [Figure 10-62] Same as above. [Figure 10-63] Same as above. [Figure 10-64] Same as above. [Figure 10-65] Same as above. [Figure 10-66] Same as above. [Figure 11] Figure 11 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of telisotuzumab. The arrows indicate the size corresponding to the IgG on the non-reducing SDS-PAGE gel. MYT4951 to MYT4989 are histidine-scanning and alanine-scanning variants of the telisotuzumab heavy chain combination. [Figure 12] Figure 12 shows the internalization and endolysosomal delivery of histidine-scanning and alanine-scanning variants of telisotuzumab in Detroit 562 cells. MYT4894 (telisotuzumab) and the heavy chain combination histidine-scanning and alanine-scanning variants MYT4953 and MYT4970 were assayed for internalization in Detroit 562 cells at the indicated time points and final concentrations of ABPC using Incucyte Human FabFluor-pH Red antibody labeling reagent. The fold increase in internalization and endolysosomal delivery is indicated by the numbers above each variant. [Figure 13a] Figures 13a-13b show the binding of histidine-scanning and alanine-scanning mutants of telisotuzumab to MET by biolayer interferometry. The histidine-scanning and alanine-scanning mutants of the heavy chain combinations MYT4953 and MYT4970 were captured on an anti-human Fc biosensor and allowed to bind to MET at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 13b] Same as above. [Figure 14] Figure 14 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning variants of telisotuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning variants of telisotuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4990 to MYT4994 are histidine-scanning and alanine-scanning variants of the telisotuzumab light chain combination. [Figure 15] Figure 15 is a table of construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 16] Figure 16 is a table of construct identifiers to SEQ ID NOs. Construct light chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 17] Figure 17 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 18] Figure 18 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 19] 19 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, paired heavy and light chain histidine scanning and alanine scanning variants, that combine light chain histidine and alanine scanning variants or light chain combination histidine scanning and alanine scanning variants with heavy chain histidine and alanine scanning variants or heavy chain combination histidine scanning and alanine scanning variants, are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 20] Figure 20 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 21]Figure 21 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 22] Figure 22 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of emibetuzumab and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT2313 represents emibetuzumab, and the remaining lanes (MYT2314 to MYT2348) represent histidine-scanning and alanine-scanning mutants of the heavy chain of emibetuzumab. [Figure 23-1] Figures 23a-23aj show binding of emibetuzumab-starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the heavy chain, MYT2313 (emibetuzumab) and MYT2314-MYT2348, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 23-2] Same as above. [Figure 23-3] Same as above. [Figure 23-4] Same as above. [Figure 23-5] Same as above. [Figure 23-6] Same as above. [Figure 23-7] Same as above. [Figure 23-8] Same as above. [Figure 23-9] Same as above. [Figure 23-10] Same as above. [Figure 23-11] Same as above. [Figure 23-12] Same as above. [Figure 23-13] Same as above. [Figure 23-14] Same as above. [Figure 23-15] Same as above. [Figure 23-16] Same as above. [Figure 23-17] Same as above. [Figure 23-18] Same as above. [Figure 23-19] Same as above. [Figure 23-20] Same as above. [Figure 23-21] Same as above. [Figure 23-22] Same as above. [Figure 23-23] Same as above. [Figure 23-24] Same as above. [Figure 23-25] Same as above. [Figure 23-26] Same as above. [Figure 23-27] Same as above. [Figure 23-28] Same as above. [Figure 23-29] Same as above. [Figure 23-30] Same as above. [Figure 23-31] Same as above. [Figure 23-32] Same as above. [Figure 23-33] Same as above. [Figure 23-34] Same as above. [Figure 23-35] Same as above. [Figure 23-36] Same as above. [Figure 24] Figure 24 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of emibetuzumab and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3958 to MYT3985 are histidine-scanning and alanine-scanning mutants of the light chain of emibetuzumab. [Figure 25-1]Figures 25a-25ab show binding of histidine-scanning and alanine-scanning mutants of emibetuzumab to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain, MYT3958-MYT3985, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 25-2] Same as above. [Figure 25-3] Same as above. [Figure 25-4] Same as above. [Figure 25-5] Same as above. [Figure 25-6] Same as above. [Figure 25-7] Same as above. [Figure 25-8] Same as above. [Figure 25-9] Same as above. [Figure 25-10] Same as above. [Figure 25-11] Same as above. [Figure 25-12] Same as above. [Figure 25-13] Same as above. [Figure 25-14] Same as above. [Figure 25-15] Same as above. [Figure 25-16] Same as above. [Figure 25-17] Same as above. [Figure 25-18] Same as above. [Figure 25-19] Same as above. [Figure 25-20] Same as above. [Figure 25-21] Same as above. [Figure 25-22] Same as above. [Figure 25-23] Same as above. [Figure 25-24] Same as above. [Figure 25-25] Same as above. [Figure 25-26] Same as above. [Figure 25-27] Same as above. [Figure 25-28] Same as above. [Figure 26]Figure 26 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of emibetuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT2848 to MYT2867 are histidine-scanning and alanine-scanning mutants of the heavy chain combination of emibetuzumab. [Figure 27a] Figures 27a-27t show binding of histidine-scanning and alanine-scanning mutants of emibetuzumab to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of heavy chain combinations MYT2848-MYT2867 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 27b] Same as above. [Figure 27c] Same as above. [Figure 27d] Same as above. [Figure 27e] Same as above. [Figure 27f] Same as above. [Figure 27g] Same as above. [Figure 27h] Same as above. [Figure 27i] Same as above. [Figure 27j] Same as above. [Figure 27k] Same as above. [Figure 27l] Same as above. [Figure 27m] Same as above. [Figure 27n] Same as above. [Figure 27o] Same as above. [Figure 27p] Same as above. [Figure 27q] Same as above. [Figure 27r] Same as above. [Figure 27s] Same as above. [Figure 27t] Same as above. [Figure 28] Figure 28 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of emibetuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4326 to MYT4345 are histidine-scanning and alanine-scanning mutants of the light chain combination of emibetuzumab. [Figure 29a] Figures 29a-29t show binding of histidine-scanning and alanine-scanning mutants of emibetuzumab to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain combinations MYT4326-MYT4345 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 29b] Same as above. [Figure 29c] Same as above. [Figure 29d] Same as above. [Figure 29e] Same as above. [Figure 29f] Same as above. [Figure 29g] Same as above. [Figure 29h] Same as above. [Figure 29i] Same as above. [Figure 29j] Same as above. [Figure 29k] Same as above. [Figure 29l] Same as above. [Figure 29m] Same as above. [Figure 29n] Same as above. [Figure 29o] Same as above. [Figure 29p] Same as above. [Figure 29q] Same as above. [Figure 29r] Same as above. [Figure 29s] Same as above. [Figure 29t] Same as above. [Figure 30] Figure 30 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of emibetuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3999 to MYT4042 are paired heavy and light chain histidine-scanning and alanine-scanning mutants of emibetuzumab, which combine histidine-scanning and alanine-scanning mutants in the light chain or combined histidine-scanning and alanine-scanning mutants in the light chain with histidine-scanning and alanine-scanning mutants in the heavy chain or combined histidine-scanning and alanine-scanning mutants in the heavy chain. [Figure 31-1] Figures 31a-31ar show the binding of histidine-scanning and alanine-scanning mutants of emibetuzumab to MET by biolayer interferometry. MYT3999-MYT4042, paired heavy and light chain histidine-scanning and alanine-scanning mutants, which combine light chain histidine-scanning and alanine-scanning mutants or light chain combinations with heavy chain histidine-scanning and alanine-scanning mutants or heavy chain combinations, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 31-2] Same as above. [Figure 31-3] Same as above. [Figure 31-4] Same as above. [Figure 31-5] Same as above. [Figure 31-6] Same as above. [Figure 31-7] Same as above. [Figure 31-8] Same as above. [Figure 31-9] Same as above. [Figure 31-10] Same as above. [Figure 31-11] Same as above. [Figure 31-12] Same as above. [Figure 31-13] Same as above. [Figure 31-14] Same as above. [Figure 31-15] Same as above. [Figure 31-16] Same as above. [Figure 31-17] Same as above. [Figure 31-18] Same as above. [Figure 31-19] Same as above. [Figure 31-20] Same as above. [Figure 31-21] Same as above. [Figure 31-22] Same as above. [Figure 31-23] Same as above. [Figure 31-24] Same as above. [Figure 31-25] Same as above. [Figure 31-26] Same as above. [Figure 31-27] Same as above. [Figure 31-28] Same as above. [Figure 31-29] Same as above. [Figure 31-30] Same as above. [Figure 31-31] Same as above. [Figure 31-32] Same as above. [Figure 31-33] Same as above. [Figure 31-34] Same as above. [Figure 31-35] Same as above. [Figure 31-36] Same as above. [Figure 31-37] Same as above. [Figure 31-38] Same as above. [Figure 31-39] Same as above. [Figure 31-40] Same as above. [Figure 31-41] Same as above. [Figure 31-42] Same as above. [Figure 31-43] Same as above. [Figure 31-44] Same as above. [Figure 32] Figure 32 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of emibetuzumab. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of emibetuzumab. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4995 to MYT5041 are histidine-scanning and alanine-scanning mutants of the emibetuzumab heavy chain combination. [Figure 33] Figure 33 is a table corresponding construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 34] Figure 34 is a table corresponding construct identifiers to SEQ ID NOs. Construct light chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 35] Figure 35 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 36] Figure 36 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 37]Figure 37 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, paired heavy and light chain histidine scanning and alanine scanning variants, that combine light chain histidine and alanine scanning variants or light chain combination histidine scanning and alanine scanning variants with heavy chain histidine and alanine scanning variants or heavy chain combination histidine scanning and alanine scanning variants, are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 38] Figure 38 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 39] Figure 39 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hucMET27Gv1.3 and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3617 represents hucMET27Gv1.3, and the remaining lanes (MYT3618 to MYT3655) represent histidine-scanning and alanine-scanning mutants of the heavy chain of hucMET27Gv1.3. [Figure 40-1] Figures 40a-40am show binding of the hucMET27Gv1.3 starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. MYT3617 (hucMET27Gv1.3) and the heavy chain histidine-scanning and alanine-scanning mutants MYT3618-MYT3655 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 40-2] Same as above. [Figure 40-3] Same as above. [Figure 40-4] Same as above. [Figure 40-5] Same as above. [Figure 40-6] Same as above. [Figure 40-7] Same as above. [Figure 40-8] Same as above. [Figure 40-9] Same as above. [Figure 40-10] Same as above. [Figure 40-11] Same as above. [Figure 40-12] Same as above. [Figure 40-13] Same as above. [Figure 40-14] Same as above. [Figure 40-15] Same as above. [Figure 40-16] Same as above. [Figure 40-17] Same as above. [Figure 40-18] Same as above. [Figure 40-19] Same as above. [Figure 40-20] Same as above. [Figure 40-21] Same as above. [Figure 40-22] Same as above. [Figure 40-23] Same as above. [Figure 40-24] Same as above. [Figure 40-25] Same as above. [Figure 40-26] Same as above. [Figure 40-27] Same as above. [Figure 40-28] Same as above. [Figure 40-29] Same as above. [Figure 40-30] Same as above. [Figure 40-31] Same as above. [Figure 40-32] Same as above. [Figure 40-33] Same as above. [Figure 40-34] Same as above. [Figure 40-35] Same as above. [Figure 40-36] Same as above. [Figure 40-37] Same as above. [Figure 40-38] Same as above. [Figure 40-39] Same as above. [Figure 41] Figure 41 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of hucMET27Gv1.3 and its histidine-scanning and alanine-scanning mutants. Arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3656 to MYT3686 are histidine-scanning and alanine-scanning mutants of the light chain of hucMET27Gv1.3. [Figure 42-1] Figures 42a-4ae show binding of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain, MYT3656-MYT3686, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 42-2] Same as above. [Figure 42-3] Same as above. [Figure 42-4] Same as above. [Figure 42-5] Same as above. [Figure 42-6] Same as above. [Figure 42-7] Same as above. [Figure 42-8] Same as above. [Figure 42-9] Same as above. [Figure 42-10] Same as above. [Figure 42-11] Same as above. [Figure 42-12] Same as above. [Figure 42-13] Same as above. [Figure 42-14] Same as above. [Figure 42-15] Same as above. [Figure 42-16] Same as above. [Figure 42-17] Same as above. [Figure 42-18] Same as above. [Figure 42-19] Same as above. [Figure 42-20] Same as above. [Figure 42-21] Same as above. [Figure 42-22] Same as above. [Figure 42-23] Same as above. [Figure 42-24] Same as above. [Figure 42-25] Same as above. [Figure 42-26] Same as above. [Figure 42-27] Same as above. [Figure 42-28] Same as above. [Figure 42-29] Same as above. [Figure 42-30] Same as above. [Figure 42-31] Same as above. [Figure 43] Figure 43 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4285 to MYT4304 are histidine-scanning and alanine-scanning mutants of the heavy chain combination of hucMET27Gv1.3. [Figure 44a] Figures 44a-44t show binding of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of heavy chain combinations MYT4285-MYT4304 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 44b] Same as above. [Figure 44c] Same as above. [Figure 44d] Same as above. [Figure 44e] Same as above. [Figure 44f] Same as above. [Figure 44g] Same as above. [Figure 44h] Same as above. [Figure 44i] Same as above. [Figure 44j] Same as above. [Figure 44k] Same as above. [Figure 44l] Same as above. [Figure 44m] Same as above. [Figure 44n] Same as above. [Figure 44o] Same as above. [Figure 44p] Same as above. [Figure 44q] Same as above. [Figure 44r] Same as above. [Figure 44s] Same as above. [Figure 44t] Same as above. [Figure 45] Figure 45 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4222 to MYT4241 are histidine-scanning and alanine-scanning mutants of the light chain combination of hucMET27Gv1.3. [Figure 46a] Figures 46a-46t show binding of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain combinations MYT4222-MYT4241 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as specified in the figures. [Figure 46b] Same as above. [Figure 46c] Same as above. [Figure 46d] Same as above. [Figure 46e] Same as above. [Figure 46f] Same as above. [Figure 46g] Same as above. [Figure 46h] Same as above. [Figure 46i] Same as above. [Figure 46j] Same as above. [Figure 46k] Same as above. [Figure 46l] Same as above. [Figure 46m] Same as above. [Figure 46n] Same as above. [Figure 46o] Same as above. [Figure 46p] Same as above. [Figure 46q] Same as above. [Figure 46r] Same as above. [Figure 46s] Same as above. [Figure 46t] Same as above. [Figure 47] Figure 47 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT5296 and MYT5042 to MYT5065 are histidine-scanning and alanine-scanning mutants of the heavy chain combination of hucMET27Gv1.3. [Figure 48]Figure 48 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT5066 to MYT5121 are histidine-scanning and alanine-scanning mutants of the light chain combination of hucMET27Gv1.3. [Figure 49a] Figures 49a-49f show the internalization and endolysosomal delivery of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3 in Detroit 562 cells. Histidine-scanning and alanine-scanning mutants of MYT4284 (hucMET27Gv1.3) and light chain combinations were assayed for internalization in Detroit 562 cells at the indicated time points and final concentrations of ABPC using Incucyte Human FabFluor-pH Red antibody labeling reagent, as specified in the figures. The fold increase in internalization and endolysosomal delivery is indicated by the numbers above each mutant. [Figure 49b] Same as above. [Figure 49c] Same as above. [Figure 49d] Same as above. [Figure 49e] Same as above. [Figure 49f] Same as above. [Figure 50a] Figures 50a-50v show the binding of histidine-scanning and alanine-scanning mutants of hucMET27Gv1.3 to MET by biolayer interferometry. The histidine-scanning and alanine-scanning mutants of the light chain combination of hucMET27Gv1.3 were captured on an anti-human Fc biosensor as indicated and allowed to bind to MET at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 50b] Same as above. [Figure 50c] Same as above. [Figure 50d] Same as above. [Figure 50e] Same as above. [Figure 50f] Same as above. [Figure 50g] Same as above. [Figure 50h] Same as above. [Figure 50i] Same as above. [Figure 50j] Same as above. [Figure 50k] Same as above. [Figure 50l] Same as above. [Figure 50m] Same as above. [Figure 50n] Same as above. [Figure 50o] Same as above. [Figure 50p] Same as above. [Figure 50q] Same as above. [Figure 50r] Same as above. [Figure 50s] Same as above. [Figure 50t] Same as above. [Figure 50u] Same as above. [Figure 50v] Same as above. [Figure 51] Figure 51 is a table of construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 52] Figure 52 is a table corresponding construct identifiers to SEQ ID NOs. Construct light chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 53]Figure 53 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 54] Figure 54 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 55] Figure 55 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 56] Figure 56 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 57] Figure 57 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of P3D12 and its histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3687 represents P3D12, and the remaining lanes (MYT3688 to MYT3726) represent histidine-scanning and alanine-scanning mutants of the heavy chain of P3D12. [Figure 58-1]Figures 58a-58an show binding of P3D12-starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. MYT3687 (P3D12) and MYT3688-MYT3726 heavy chain histidine-scanning and alanine-scanning mutants were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 58-2] Same as above. [Figure 58-3] Same as above. [Figure 58-4] Same as above. [Figure 58-5] Same as above. [Figure 58-6] Same as above. [Figure 58-7] Same as above. [Figure 58-8] Same as above. [Figure 58-9] Same as above. [Figure 58-10] Same as above. [Figure 58-11] Same as above. [Figure 58-12] Same as above. [Figure 58-13] Same as above. [Figure 58-14] Same as above. [Figure 58-15] Same as above. [Figure 58-16] Same as above. [Figure 58-17] Same as above. [Figure 58-18] Same as above. [Figure 58-19] Same as above. [Figure 58-20] Same as above. [Figure 58-21] Same as above. [Figure 58-22] Same as above. [Figure 58-23] Same as above. [Figure 58-24] Same as above. [Figure 58-25] Same as above. [Figure 58-26] Same as above. [Figure 58-27] Same as above. [Figure 58-28] Same as above. [Figure 58-29] Same as above. [Figure 58-30] Same as above. [Figure 58-31] Same as above. [Figure 58-32] Same as above. [Figure 58-33] Same as above. [Figure 58-34] Same as above. [Figure 58-35] Same as above. [Figure 58-36] Same as above. [Figure 58-37] Same as above. [Figure 58-38] Same as above. [Figure 58-39] Same as above. [Figure 58-40] Same as above. [Figure 59] Figure 59 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of P3D12 and histidine-scanning and alanine-scanning mutants. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT3727 to MYT3754 are histidine-scanning and alanine-scanning mutants of the light chain of P3D12. [Figure 60-1] Figures 60a-60ab ​​show binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain, MYT3727-MYT3754, were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figure. [Figure 60-2] Same as above. [Figure 60-3] Same as above. [Figure 60-4] Same as above. [Figure 60-5] Same as above. [Figure 60-6] Same as above. [Figure 60-7] Same as above. [Figure 60-8] Same as above. [Figure 60-9] Same as above. [Figure 60-10] Same as above. [Figure 60-11] Same as above. [Figure 60-12] Same as above. [Figure 60-13] Same as above. [Figure 60-14] Same as above. [Figure 60-15] Same as above. [Figure 60-16] Same as above. [Figure 60-17] Same as above. [Figure 60-18] Same as above. [Figure 60-19] Same as above. [Figure 60-20] Same as above. [Figure 60-21] Same as above. [Figure 60-22] Same as above. [Figure 60-23] Same as above. [Figure 60-24] Same as above. [Figure 60-25] Same as above. [Figure 60-26] Same as above. [Figure 60-27] Same as above. [Figure 60-28] Same as above. [Figure 61] Figure 61 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of P3D12. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4306 to MYT4325 are histidine-scanning and alanine-scanning mutants of the heavy chain combination of P3D12. [Figure 62a]Figures 62a-62t show binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the heavy chain combinations MYT4306-MYT4325 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 62b] Same as above. [Figure 62c] Same as above. [Figure 62d] Same as above. [Figure 62e] Same as above. [Figure 62f] Same as above. [Figure 62g] Same as above. [Figure 62h] Same as above. [Figure 62i] Same as above. [Figure 62j] Same as above. [Figure 62k] Same as above. [Figure 62l] Same as above. [Figure 62m] Same as above. [Figure 62n] Same as above. [Figure 62o] Same as above. [Figure 62p] Same as above. [Figure 62q] Same as above. [Figure 62r] Same as above. [Figure 62s] Same as above. [Figure 62t] Same as above. [Figure 63] Figure 63 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of P3D12. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT4242 to MYT4261 are histidine-scanning and alanine-scanning mutants of the light chain combination of P3D12. [Figure 64a] Figures 64a-64t show binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of the light chain combinations MYT4242-MYT4261 were captured on an anti-human Fc biosensor and allowed to bind to MET at low or high pH, ​​as indicated in the figures. [Figure 64b] Same as above. [Figure 64c] Same as above. [Figure 64d] Same as above. [Figure 64e] Same as above. [Figure 64f] Same as above. [Figure 64g] Same as above. [Figure 64h] Same as above. [Figure 64i] Same as above. [Figure 64j] Same as above. [Figure 64k] Same as above. [Figure 64l] Same as above. [Figure 64m] Same as above. [Figure 64n] Same as above. [Figure 64o] Same as above. [Figure 64p] Same as above. [Figure 64q] Same as above. [Figure 64r] Same as above. [Figure 64s] Same as above. [Figure 64t] Same as above. [Figure 65] Figure 65 shows SDS PAGE of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of P3D12. The arrows indicate the size corresponding to IgG on the non-reducing SDS PAGE gel. MYT5122 to MYT5221 are histidine-scanning and alanine-scanning mutants of the heavy chain combination of P3D12. [Figure 66a] Figures 66a-66e show the internalization and endolysosomal delivery of histidine-scanning and alanine-scanning mutants of P3D12 in Detroit 562 cells. Histidine-scanning and alanine-scanning mutants of MYT4305 (P3D12) and heavy chain combinations were assayed for internalization in Detroit 562 cells at the indicated time points and final concentrations of ABPC using Incucyte Human FabFluor-pH Red antibody labeling reagent, as specified in the figures. The fold increase in internalization and endolysosomal delivery is indicated by the numbers above each mutant. [Figure 66b] Same as above. [Figure 66c] Same as above. [Figure 66d] Same as above. [Figure 66e] Same as above. [Figure 67a] Figures 67a-67e show the binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. Histidine-scanning and alanine-scanning mutants of P3D12 heavy chain combinations were captured on an anti-human Fc biosensor as indicated and allowed to bind to MET at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 67b] Same as above. [Figure 67c] Same as above. [Figure 67d] Same as above. [Figure 67e] Same as above. [Figure 68]Figure 68 shows SDS PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm the expression of histidine-scanning and alanine-scanning mutants of P3D12. The arrows indicate the size corresponding to IgG on the non-reducing SDS PAGE gel. MYT5222 to MYT5295 are histidine-scanning and alanine-scanning mutants of the light chain combination of P3D12. [Figure 69] Figure 69 shows the internalization and endolysosomal delivery of histidine-scanning and alanine-scanning mutants of P3D12 in Detroit 562 cells. MYT4305 (P3D12) and a light chain combination histidine-scanning and alanine-scanning mutant of P3D12, MYT5237, were assayed for internalization in Detroit 562 cells at the indicated time points and final concentrations of ABPC using Incucyte Human FabFluor-pH Red antibody labeling reagent. The fold increase in internalization and endolysosomal delivery is indicated by the numbers above each mutant. [Figure 70] Figure 70 shows the binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. MYT5237, a histidine-scanning and alanine-scanning mutant of the light chain combination of P3D12, was captured on an anti-human Fc biosensor and allowed to bind to MET at pH 7.4. Dissociation occurred at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 71] Figure 71 is a table of construct identifiers to SEQ ID NOs. Construct heavy chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 72]Figure 72 is a table corresponding construct identifiers to SEQ ID NOs. Construct light chain histidine-scanning and alanine-scanning mutants are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 73] Figure 73 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 74] Figure 74 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 75a] Figure 75 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of heavy chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 75b] Same as above. [Figure 76a] Figure 76 is a table of construct identifiers to SEQ ID NOs. Constructs, histidine-scanning and alanine-scanning mutants of light chain combinations are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 76b] Same as above. [Figure 77]Figure 77 is an SDS PAGE of reformatted anti-MET ABPC. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS PAGE gel to confirm expression of the starting ABPC and the histidine-scanning and alanine-scanning mutants. The arrow indicates the size corresponding to the IgG on the non-reducing SDS PAGE gel. [Figure 78a] Figures 78a-78l show the binding of starting ABPC and histidine-scanning and alanine-scanning mutants to MET by biolayer interferometry. Starting ABPC and histidine-scanning and alanine-scanning mutants were captured on an anti-human Fc biosensor as indicated and allowed to bind to MET at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 78b] Same as above. [Figure 78c] Same as above. [Figure 78d] Same as above. [Figure 78e] Same as above. [Figure 78f] Same as above. [Figure 78g] Same as above. [Figure 78h] Same as above. [Figure 78i] Same as above. [Figure 78j] Same as above. [Figure 78k] Same as above. [Figure 78l] Same as above. [Figure 79a]Figures 79a-79f are internalization and endolysosomal delivery of starting anti-MET ABPC and histidine-scanning and alanine-scanning variants in Detroit 562 cells. Starting ABPC and histidine-scanning and alanine-scanning variants were assayed for internalization in Detroit 562 cells at the indicated time points and final concentrations of ABPC using Incucyte Human FabFluor-pH Red Antibody Labeling Reagent, as specified in the figures. The fold increase in internalization and endolysosomal delivery is indicated by the numbers above each variant. [Figure 79b] Same as above. [Figure 79c] Same as above. [Figure 79d] Same as above. [Figure 79e] Same as above. [Figure 79f] Same as above. [Figure 80a] Figures 80a-80d are tables of identifier correspondence for reformatted ABPC constructs. The IgG1 starting ABPC and histidine-scanning and alanine-scanning mutants are listed in the first column of the table. IgG1s with TH and YTE mutations, with the same heavy and light chain variable regions as the IgG1 construct in the same row, are listed in the second column. [Figure 80b] Same as above. [Figure 80c] Same as above. [Figure 80d] Same as above. [Figure 81-1] Figure 81. Internalization of anti-MET mAb in cells. pH-engineered anti-MET antibody variants, the corresponding starting ABPC antibody, and a control IgG1 isotype control (BP0297, Bioxcell) were assayed for internalization and endolysosomal delivery as measured by mean fluorescence intensity on cells as specified in Figures 81a-81aj, along with a vehicle control, at 24 hours. Error bars represent standard deviation. Each number above the bar represents the fold change relative to the corresponding starting ABPC. [Figure 81-2] Same as above. [Figure 81-3] Same as above. [Figure 81-4] Same as above. [Figure 81-5] Same as above. [Figure 81-6] Same as above. [Figure 81-7] Same as above. [Figure 81-8] Same as above. [Figure 81-9] Same as above. [Figure 81-10] Same as above. [Figure 81-11] Same as above. [Figure 81-12] Same as above. [Figure 81-13] Same as above. [Figure 81-14] Same as above. [Figure 81-15] Same as above. [Figure 81-16] Same as above. [Figure 81-17] Same as above. [Fig. 81-18] Same as above. [Figure 81-19] Same as above. [Figure 81-20] Same as above. [Figure 81-21] Same as above. [Fig. 81-22] Same as above. [Figure 81-23] Same as above. [Fig. 81-24] Same as above. [Fig. 81-25] Same as above. [Fig. 81-26] Same as above. [Fig. 81-27] Same as above. [Fig. 81-28] Same as above. [Fig. 81-29] Same as above. [Fig. 81-30] Same as above. [Fig. 81-31] Same as above. [Fig. 81-32] Same as above. [Fig. 81-33] Same as above. [Fig. 81-34] Same as above. [Fig. 81-35] Same as above. [Fig. 81-36] Same as above. [Figure 82]Figure 82 shows SDS-PAGE analysis of histidine-scanning and alanine-scanning mutants of P3D12. Harvested Expi293 cell culture supernatant was loaded onto a non-reducing SDS-PAGE gel to confirm the expression of the histidine-scanning and alanine-scanning mutants of P3D12. The arrows indicate the size corresponding to IgG on the non-reducing SDS-PAGE gel. MYT5342 to MYT5381 are paired heavy and light chain histidine-scanning and alanine-scanning mutants of P3D12, which combine light chain histidine- and alanine-scanning mutants or light chain combination histidine-scanning and alanine-scanning mutants with heavy chain histidine- and alanine-scanning mutants or heavy chain combination histidine-scanning and alanine-scanning mutants. [Figure 83-1] Figures 83a-83an show the binding of histidine-scanning and alanine-scanning mutants of P3D12 to MET by biolayer interferometry. Paired heavy and light chain histidine-scanning and alanine-scanning mutants, MYT5342-MYT5381, in which light chain histidine-scanning and alanine-scanning mutants or light chain combinations of histidine-scanning and alanine-scanning mutants were combined with heavy chain histidine-scanning and alanine-scanning mutants or heavy chain combinations of histidine-scanning and alanine-scanning mutants, were captured on an anti-human Fc biosensor and allowed to bind to MET at pH 7.4. Dissociation was at pH 7.4 (black trace) or pH 5.4 (gray trace). [Figure 83-2] Same as above. [Figure 83-3] Same as above. [Figure 83-4] Same as above. [Figure 83-5] Same as above. [Figure 83-6] Same as above. [Figure 83-7] Same as above. [Figure 83-8] Same as above. [Figure 83-9] Same as above. [Figure 83-10] Same as above. [Figure 83-11] Same as above. [Figure 83-12] Same as above. [Figure 83-13] Same as above. [Figure 83-14] Same as above. [Figure 83-15] Same as above. [Figure 83-16] Same as above. [Figure 83-17] Same as above. [Figure 83-18] Same as above. [Figure 83-19] Same as above. [Figure 83-20] Same as above. [Figure 83-21] Same as above. [Figure 83-22] Same as above. [Figure 83-23] Same as above. [Figure 83-24] Same as above. [Fig. 83-25] Same as above. [Figure 83-26] Same as above. [Figure 83-27] Same as above. [Fig. 83-28] Same as above. [Fig. 83-29] Same as above. [Figure 83-30] Same as above. [Figure 83-31] Same as above. [Fig. 83-32] Same as above. [Figure 83-33] Same as above. [Fig. 83-34] Same as above. [Fig. 83-35] Same as above. [Fig. 83-36] Same as above. [Figure 83-37] Same as above. [Fig. 83-38] Same as above. [Fig. 83-39] Same as above. [Figure 83-40] Same as above. [Figure 84]Figure 84 is a table corresponding construct identifiers to SEQ ID NOs. Constructs, paired heavy and light chain histidine scanning and alanine scanning variants, that combine light chain histidine and alanine scanning variants or light chain combination histidine scanning and alanine scanning variants with heavy chain histidine and alanine scanning variants or heavy chain combination histidine scanning and alanine scanning variants, are listed in the first column of the table, with corresponding SEQ ID NOs listed for the construct on the left and the appropriate heavy and / or light chain category along the top. [Figure 85] Figure 85 shows the melting temperatures of selected anti-MET mAbs. Selected anti-MET mAbs were assayed for melting temperatures by differential scanning fluorimetry (DSF), and the resulting Sypro Orange signal was plotted as its first derivative. Melting temperatures (Tm) were calculated as the maximum of this graph and are tabulated. DETAILED DESCRIPTION OF THE INVENTION

[0072] Provided herein is an antigen-binding protein construct (ABPC) comprising a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, and / or (b) the dissociation constant (K D ) at pH 7.0 to 8.0 D The antigen binding protein constructs (ABPCs) are provided, which are larger than or equal to 1. In some embodiments of these ABPCs, the ABPC is degraded in the target mammalian cell after internalization of the ABPC by the target mammalian cell. Some embodiments of any of the ABPCs described herein may further include a conjugated toxin, radioisotope, drug, or small molecule (e.g., a fluorophore or dye).

[0073] Also provided is an antigen-binding protein construct (ABPC) comprising a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0, and / or the dissociation constant (K) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than or equal to 0.0. D ) at pH 7.0 to 8.0 D and (b) a composition comprising the ABPC results in one or more (e.g., two or three) of: increased (e.g., a detectable increase) in toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPC; increased (e.g., a detectable increase) in killing of target mammalian cells compared to a composition comprising the same amount of control ABPC; and increased (e.g., a detectable increase) in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPC.

[0074] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine, and a light chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of telisotuzumab comprises SEQ ID NO: 1. In some embodiments of any of the ABPCs described herein, the light chain variable domain of telisotuzumab comprises SEQ ID NO: 2.

[0075] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 3 to 5 have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, whereby a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 6 to 8 have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 3 to 5 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 6 to 8 have been substituted with histidine.

[0076] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101.In some embodiments of any of the ABPCs described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1 and contains a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107. and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acid positions of SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101.

[0077] In some embodiments of any of the ABPCs described herein, the heavy chain variable domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1. [Table 1] TIFF2025072609000003.tif207150

[0078] In some embodiments of any of the ABPCs described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:2 listed in Table 2.

[0079] In some examples of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and the light chain variable domain comprises an alanine at position 38 of SEQ ID NO:2.

[0080] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, and that comprises an alanine at position 38 of SEQ ID NO:2; and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1. 1, wherein the heavy chain variable domain is at least 99%, at least 99%, or 100% identical to the heavy chain variable domain of SEQ ID NO: 1, and wherein the heavy chain variable domain comprises a histidine at one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acid positions selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107.

[0081] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101, and wherein the light chain variable domain comprises an alanine at position 38 of SEQ ID NO:2. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain is a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2 and contains a histidine at one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acid positions of SEQ ID NO:2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101. and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and that comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO:1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103, and 107.

[0082] In some embodiments of any of the ABPCs described herein, the light chain variable domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:2 listed in Table 2, and the light chain variable domain comprises an alanine at position 38 of SEQ ID NO:2. [Table 2] TIFF2025072609000005.tif228150TIFF2025072609000006.tif228150TIFF2025072609000007.tif228150TIFF2025072609000008.tif28150

[0083] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1; and a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:2 listed in Table 2.

[0084] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:2 and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, and that includes a histidine at any of the specific combinations of one or more (e.g., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions of SEQ ID NO:1 listed in Table 1.

[0085] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 25 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0086] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 28 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0087] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 29 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0088] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 30 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0089] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 31 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0090] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 32 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0091] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 34 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0092] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 35 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0093] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 36 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0094] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 37 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0095] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 54 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0096] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 55 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0097] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 59 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0098] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 60 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0099] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 95 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0100] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 99 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0101] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises a histidine at position 101 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0102] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% identical to SEQ ID NO:2, wherein the light chain variable domain comprises an alanine at position 38 of SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the heavy chain variable domain comprises a histidine at any of the specific combinations of one or more amino acid positions of SEQ ID NO:1 listed in Table 1.

[0103] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine, and a light chain variable domain of telisotuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) histidines have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of telisotuzumab comprises SEQ ID NO: 1. In some embodiments of any of the ABPCs described herein, the light chain variable domain of telisotuzumab comprises SEQ ID NO: 2.

[0104] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs:3-5 have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs:6-8 have been substituted with alanine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 3 to 5 have been substituted with alanine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NOs: 6 to 8 have been substituted with alanine.

[0105] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0106] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0107] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:2 and a heavy chain variable domain comprising SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0108] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:51 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0109] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:52 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0110] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:53 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0111] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:54 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0112] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:55 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0113] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:56 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0114] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:57 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0115] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:58 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0116] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:59 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0117] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:60 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0118] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:61 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0119] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:62 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0120] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:63 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0121] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:64 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0122] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:65 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0123] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:66 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0124] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:67 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0125] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:68 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0126] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:69 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0127] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:70 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0128] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:71 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0129] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:72 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0130] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:73 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0131] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:74 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0132] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:75; and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0133] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:76 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0134] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:77 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0135] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:78 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0136] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:79 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0137] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:80 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0138] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:81 and a heavy chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0139] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain is selected from the group consisting of SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, and a heavy chain variable domain comprising SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0140] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:82 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0141] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:83 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0142] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:84 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0143] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:85 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0144] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:86 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0145] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:87 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0146] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:88 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0147] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:89 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0148] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:90 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0149] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:91 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0150] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:92 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0151] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:93 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0152] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:94 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0153] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:95 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0154] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:96 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0155] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:97 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0156] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:98 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0157] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:99 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0158] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:100 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0159] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:101 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0160] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:102 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0161] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:103 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0162] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:104 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0163] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:105 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0164] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:106 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0165] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:107 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0166] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:108 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0167] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:109 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0168] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:110 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0169] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:111 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0170] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:112 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0171] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:113 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0172] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:114 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0173] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:115 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0174] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:116 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0175] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:117 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0176] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:118 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0177] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:119 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0178] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:120 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0179] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:121 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0180] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:122 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0181] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:123 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0182] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:124 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0183] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:125 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0184] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:126 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0185] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:127 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0186] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:128 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0187] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:129 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0188] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising SEQ ID NO:130 and a light chain variable domain comprising SEQ ID NO:2, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0189] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, or SEQ ID NO:145.

[0190] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:131 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0191] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:132 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0192] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:133 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0193] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:134 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0194] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:135 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0195] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:136 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0196] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:137 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0197] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:138 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0198] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:139 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0199] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:140 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0200] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:141 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0201] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:142 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0202] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:143 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0203] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:144 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0204] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain comprising SEQ ID NO:145 and a light chain variable domain comprising SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, and a heavy chain variable domain comprising SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, or SEQ ID NO:130.

[0205] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of emibetuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain of emibetuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain of emibetuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine, and a light chain variable domain of emibetuzumab in which one or more (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acids have been substituted with histidine. In some embodiments of any of the ABPCs described herein, the heavy chain variable domain of emibetuzumab comprises SEQ ID NO: 146. In some embodiments of any of the ABPCs described herein, the light chain variable domain of emibetuzumab comprises SEQ ID NO: 147.

[0206] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain including CDR1, CDR2, and CDR3 set forth in SEQ ID NO: 148, SEQ ID NO: 149, and SEQ ID NO: 150, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 148-150 are substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain including CDR1, CDR2, and CDR3 which are set forth in SEQ ID NO: 151, SEQ ID NO: 152, and SEQ ID NO: 153, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 151-153 are substituted with histidine. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 148, 149, and 150, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 148 to 150 have been substituted with histidine; and a light chain variable domain comprising CDR1, CDR2, and CDR3 set forth in SEQ ID NOs: 151, 152, and 153, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 151 to 153 have been substituted with histidine.

[0207] In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a heavy chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 146, and the heavy chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103. In some embodiments of any of the ABPCs described herein, the first antigen-binding domain comprises a light chain variable domain that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 147, and the light chain variable domain comprises a histidine at one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acid positions of SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97.In some embodiments of any of the ABPCs described herein, the first antigen-binding domain is a heavy chain variable domain that is at least 90% ...

Claims

1. A nucleic acid encoding an antigen binding protein construct (ABPC), the ABPC comprising: a first antigen-binding domain capable of specifically binding to MET or an epitope of MET present on the surface of a target mammalian cell; the first antigen-binding domain comprises: (a) a heavy chain variable domain comprising a heavy chain CDR of SEQ ID NO: 1, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103 and 107, and a light chain variable domain comprising a light chain CDR of SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99 and 101; a heavy chain variable domain comprising the heavy chain CDRs in SEQ ID NO:1, said heavy chain variable domain comprising a histidine at one or more positions in SEQ ID NO:1 selected from the group consisting of 26, 27, 28, 29, 32, 97, 98, 99, 100, 101, 102, 103 and 107, and a light chain variable domain comprising the light chain CDRs in SEQ ID NO:2; or a heavy chain variable domain comprising the heavy chain CDRs in SEQ ID NO: 1 and a light chain variable domain comprising the light chain CDRs in SEQ ID NO: 2, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of 25, 28, 29, 30, 31, 32, 34, 35, 36, 37, 54, 55, 59, 60, 95, 99, and 101; (b) a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 146, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 147, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97; a heavy chain variable domain comprising the heavy chain CDRs in SEQ ID NO: 146, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 146 selected from the group consisting of 31, 50, 51, 52, 53, 54, 56, 57, 59, 98, 99, 100, and 103, and a light chain variable domain comprising the light chain CDRs in SEQ ID NO: 147; or a heavy chain variable domain comprising the heavy chain CDRs in SEQ ID NO: 146 and a light chain variable domain comprising the light chain CDRs in SEQ ID NO: 147, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 147 selected from the group consisting of 25, 26, 29, 32, 33, 51, 91, 92, 95, 96, and 97; (c) a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO: 304, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 304 selected from the group consisting of 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 105, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO: 305, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:304, comprising a histidine at one or more positions in SEQ ID NO:304 selected from the group consisting of: 27, 34, 35, 50, 51, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 98, 99, 103, and 105, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:305; or a heavy chain variable domain comprising the heavy chain CDRs in SEQ ID NO: 304 and a light chain variable domain comprising the light chain CDRs in SEQ ID NO: 305, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO: 305 selected from the group consisting of 26, 30, 31, 34, 36, 54, 56, 57, 60, 93, 95, 99, and 101; or (d) a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:502, wherein the heavy chain variable domain comprises a histidine at one or more positions in SEQ ID NO:502 selected from the group consisting of: 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101, 102, 103, 106, and 107, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:503, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:503 selected from the group consisting of: 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98; a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:502, comprising a histidine at one or more positions in SEQ ID NO:502 selected from the group consisting of: 27, 29, 30, 32, 33, 34, 50, 51, 52, 53, 57, 59, 98, 100, 101, 102, 103, 106, and 107, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:503; or a heavy chain variable domain comprising the heavy chain CDRs of SEQ ID NO:502, and a light chain variable domain comprising the light chain CDRs of SEQ ID NO:503, wherein the light chain variable domain comprises a histidine at one or more positions in SEQ ID NO:503 selected from the group consisting of 25, 29, 31, 32, 33, 34, 35, 52, 55, 91, 92, 93, 94, 95, 96, 97, and 98; Including, (i) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or (ii) a nucleic acid, wherein the dissociation constant (K D ) of said first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the K D at a pH of about 7.0 to about 8.

0.

2. The nucleic acid described in claim 1, wherein the ABPC is degraded in the target mammalian cell after intracellular translocation of the ABPC by the target mammalian cell.

3. The first antigen-binding domain comprises one of the following (a) to (d): (a) a light chain variable domain of SEQ ID NO:2, SEQ ID NO:52, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, or SEQ ID NO:140, and / or A heavy chain variable domain of SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:50, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:94, or SEQ ID NO:111, the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain of SEQ ID NO: 1; (ii) does not comprise a light chain variable domain of SEQ ID NO: 2 and a heavy chain variable domain that is not one of SEQ ID NOs: 13-16, 19, 40-46, 50, 82-84, 86, 87, 89, 90, 94, and 111; or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not one of SEQ ID NOs: 52, 55-59, 61-67, 71, 72, 75, 79, 81, and 131-140; the light chain variable domain and / or the heavy chain variable domain; (b) a light chain variable domain of SEQ ID NO:147, SEQ ID NO:190, SEQ ID NO:191, SEQ ID NO:194, SEQ ID NO:197, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:201, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:213, SEQ ID NO:214, SEQ ID NO:215, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:300, or SEQ ID NO:301, and / or a heavy chain variable domain of SEQ ID NO:146, SEQ ID NO:159, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:187, SEQ ID NO:217, SEQ ID NO:218, SEQ ID NO:219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, or SEQ ID NO:236; the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain of SEQ ID NO: 146; (ii) does not comprise a light chain variable domain of SEQ ID NO: 147 and a heavy chain variable domain that is not one of SEQ ID NOs: 159, 164-168, 170, 171, 173, 182-184, 187, 217-228, and 230-236; or (iii) does not comprise a heavy chain variable domain of SEQ ID NO: 146 and a light chain variable domain that is not one of SEQ ID NOs: 190, 191, 194, 197, 198, 200, 201, 209, 210, 213-215, 284-298, 300, and 301; the light chain variable domain and / or the heavy chain variable domain; (c) SEQ ID NO: 305, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 360, SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 365, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 374, SEQ ID NO: 378, SEQ ID NO: 380, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430, SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436, SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, and / or the light chain variable domain of SEQ ID NO:441, SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:450, SEQ ID NO:451, SEQ ID NO:453, SEQ ID NO:457, SEQ ID NO:462, SEQ ID NO:463, SEQ ID NO:465, SEQ ID NO:470, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:476, SEQ ID NO:479, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:485, SEQ ID NO:490, SEQ ID NO:492, SEQ ID NO:494, SEQ ID NO:496, or SEQ ID NO:499; and / or a heavy chain variable domain of SEQ ID NO:304, SEQ ID NO:313, SEQ ID NO:320, SEQ ID NO:321, SEQ ID NO:322, SEQ ID NO:323, SEQ ID NO:324, SEQ ID NO:326, SEQ ID NO:327, SEQ ID NO:328, SEQ ID NO:329, SEQ ID NO:330, SEQ ID NO:331, SEQ ID NO:332, SEQ ID NO:333, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:345, SEQ ID NO:347, SEQ ID NO:381, SEQ ID NO:382, SEQ ID NO:383, SEQ ID NO:384, SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389, SEQ ID NO:390, SEQ ID NO:392, SEQ ID NO:393, SEQ ID NO:395, SEQ ID NO:396, SEQ ID NO:397, SEQ ID NO:398, SEQ ID NO:399, or SEQ ID NO:400; the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain of SEQ ID NO: 304; (ii) does not comprise a light chain variable domain of SEQ ID NO: 305 and a heavy chain variable domain that is not one of SEQ ID NOs: 313, 320-324, 326-337, 340, 341, 345, 347, 381-390, 392, 393, and 395-400; or (iii) does not comprise a light chain variable domain of SEQ ID NO:

304. and a light chain variable domain which is not one of SEQ ID NOs: 352, 356, 357, 360, 362, 364, 365, 367, 368, 371, 372, 374, 378, 380, 428-446, 450, 451, 453, 457, 462, 463, 465, 470, 472-474, 476, 479, 482, 483, 485, 490, 492, 494, 496, and 499. the light chain variable domain and / or the heavy chain variable domain; and (d) a light chain variable domain of SEQ ID NO:503, SEQ ID NO:550, SEQ ID NO:554, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:562, SEQ ID NO:565, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO:703, SEQ ID NO:704, SEQ ID NO:705, SEQ ID NO:706, SEQ ID NO:707, SEQ ID NO:708, SEQ ID NO:709, SEQ ID NO:710, SEQ ID NO:711, SEQ ID NO:712, SEQ ID NO:713, or SEQ ID NO:732, and / or a heavy chain variable domain of SEQ ID NO:502, SEQ ID NO:511, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, SEQ ID NO:522, SEQ ID NO:523, SEQ ID NO:527, SEQ ID NO:529, SEQ ID NO:538, SEQ ID NO:540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:546, SEQ ID NO:547, SEQ ID NO:578, SEQ ID NO:579, SEQ ID NO:580, SEQ ID NO:581, SEQ ID NO:582, SEQ ID NO:583, SEQ ID NO:584, SEQ ID NO:585, SEQ ID NO:586, SEQ ID NO:587, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:590, SEQ ID NO:591, SEQ ID NO:592, SEQ ID NO:593, SEQ ID NO:594, SEQ ID NO:595, SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:606, SEQ ID NO:621, SEQ ID NO:659 or SEQ ID NO:676; the first antigen-binding domain (i) does not comprise a light chain variable domain of SEQ ID NO:503 and a heavy chain variable domain of SEQ ID NO:502; or (ii) does not comprise a light chain variable domain of SEQ ID NO:503 and a heavy chain variable domain that is not one of SEQ ID NOs:511, 513, 514, 516-523, 527, 529, 538, 540-543, 546, 547, 578-597, 606, 621, 659, and 676; or (iii) does not comprise a heavy chain variable domain of SEQ ID NO:502 and a light chain variable domain that is not one of SEQ ID NOs:550, 554, 556-560, 562, 565, 569, 570-576, 697-713, and 732; the light chain variable domain and / or the heavy chain variable domain The nucleic acid according to claim 1 or 2, comprising one of the following:

4. A nucleic acid described in any one of claims 1 to 3, wherein a composition comprising the ABPC provides increased endolysosomal delivery in the target mammalian cell compared to a composition comprising an equivalent amount of a control ABPC.

5. The composition comprising the ABPC, does not cause a significant decrease in the level of MET present on the surface of said target mammalian cells compared to a composition comprising an equivalent amount of a control ABPC; or The nucleic acid of any one of claims 1 to 4, which does not result in a detectable decrease in the level of MET present at the surface of the target mammalian cell.

6. The nucleic acid described in any one of claims 1 to 5, wherein the target mammalian cell is a cancer cell.

7. The ABPC, is cross-reactive with non-human primate MET and human MET, or The nucleic acid of any one of claims 1 to 6, which is cross-reactive with non-human primate MET, human MET, and one or both of rat MET and mouse MET.

8. A nucleic acid described in any one of claims 1 to 7, wherein the ABPC comprises a single polypeptide.

9. The nucleic acid described in claim 8, wherein the first antigen-binding domain is selected from the group consisting of a VH domain, a VHH domain, a VNAR domain, and an scFv.

10. The nucleic acid described in claim 8 or 9, wherein the ABPC further comprises a second antigen binding domain.

11. A nucleic acid described in any one of claims 1 to 7, wherein the ABPC comprises two or more polypeptides.

12. The nucleic acid described in claim 10, wherein the ABPC is an antibody.

13. The nucleic acid described in claim 11 or 12, wherein the ABPC further comprises a second antigen binding domain.

14. An expression vector comprising a nucleic acid described in any one of claims 1 to 10.

15. A cell comprising the expression vector described in claim 14.

16. A method for producing an antigen-binding antibody construct, comprising: Culturing the cell of claim 15 in a culture medium; and isolating said ABPCs from said cells or said culture medium. A method comprising:

17. An expression vector pair comprising both a nucleic acid described in any one of claims 1 to 7 and 11 to 13.

18. A cell comprising the expression vector pair described in claim 17.

19. A method for producing an antigen-binding antibody construct, comprising: Culturing the cell of claim 18 in a culture medium; and isolating said ABPCs from said cells or said culture medium. A method comprising:

Images