P75 neurotrophin receptor (p75NTR)-binding proteins and p75NTR-mediated delivery to the nervous system

Abstract

The present invention provides anti-p75 neurotrophin receptor (p75NTR) antigen-binding proteins and protein-drug conjugates including an anti-p75NTR antigen-binding protein conjugated to a molecular cargo, as well as methods of treating diseases with such antigen-binding proteins and protein-drug conjugates.

Description

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This patent application claims the benefit of U.S. Provisional Application No. 63 / 619,934, filed January 11, 2024, and U.S. Provisional Application No. 63 / 672,471, filed July 17, 2024, the disclosure of each of which is incorporated by reference herein in its entirety for all purposes. SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on January 6, 2025, is named 250298_000780_SL.xml and is 741,077 bytes in size. FIELD OF THE INVENTION

[0003] The present invention relates to p75 neurotrophin receptor (p75NTR) antigen-binding proteins and protein-drug conjugates including a p75NTR antigen-binding protein conjugated to a molecular cargo, as well as method of treating diseases with such antigen-binding proteins and protein-drug conjugates. BACKGROUND OF THE INVENTION

[0004] The development of drug delivery approaches to improve safety and efficacy of nervous system therapeutics is an increasingly critical and evolving field. Overcoming the blood-brain barrier (BBB) has been a challenge for the delivery of therapeutics to the brain. While the peripheral nervous system (PNS) does not have a BBB, it has been very challenging to appropriately deliver therapeutics to cells of interest in the PNS. Safe and efficacious nervous system therapeutics also require appropriate pharmacokinetic / pharmacodynamic (PK / PD) properties of the therapeutic in the nervous tissue of interest and limited potential effects on other regions of the nervous system. Moreover, the options for achieving retrograde targeting for therapeutic delivery are limited.

[0005] Effective delivery of therapeutics to the nervous system may provide potential treatment opportunities for chronic pain and itch indications and otherwise uncurable diseases such as spinal cord degeneration, amyotrophic lateral sclerosis (ALS), and neurodegenerative diseases such as Alzheimer’s disease (AD). SUMMARY OF THE INVENTION

[0006] As mentioned in the background section above, there is an unmet need in the art to develop effective means to deliver therapeutics to the nervous system, such as to the peripheral nervous system (PNS), of a subject. This application provides compositions and methods to address this and other related needs.

[0007] In one aspect, provided herein is an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), wherein the antigen-binding protein exhibits less than 50% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay.

[0008] In some embodiments, the cell-based assay comprises the steps of: a) incubating a soluble extracellular domain of human p75NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75NTR is fused to an Fc domain of IgG, b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter. c) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), and d) calculating % inhibition using the formula DJ TT                        _ D[ IT 100 X                                  1X1-1Usoluble p75 RLUNGF — RLUsoluble p75 wherein, RLUsoiubie P75 is the RLU value from cells treated under the same conditions with an antigen-binding protein which does not bind to p75NTR, and RLUngf is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75NTR.

[0009] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

[0010] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and / or (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof.

[0011] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

[0012] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and / or (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof.

[0013] In one aspect, provided herein is an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), comprising: (i) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and / or (ii) a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251,269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597, or a variant thereof.

[0014] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof; (37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof; (38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof; (39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or (40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

[0015] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof; (16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof; (17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof; (18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or (28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0016] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or (7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0017] In some embodiments, the antigen-binding protein comprises: (1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and / or (6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0018] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, ora variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and a LCVR that comprises: an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (29) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (30) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (31) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and a LCVR that comprises: LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (32) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (33) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (34) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (35) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (36) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof; (37) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof; (38) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof; (39) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; (40) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof.

[0019] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof; (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof; (8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof; (10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof; (11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof; (12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof; (13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof; (14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof; (15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof; (16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof; (17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof; (18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; (27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and / or (28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

[0020] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, ora variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and / or (7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

[0021] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof; (2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof; (3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof; (4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof; (5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; and / or (6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and / or a LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

[0022] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof; (11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof; (13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof; (15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof; (17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof; (18) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 323, or a variant thereof; (19) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 339, or a variant thereof; (20) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 357, or a variant thereof; (21) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 377, or a variant thereof; (22) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 391, or a variant thereof; (23) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (24) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (25) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (26) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (27) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (28) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; acid sequence set forth in SEQ ID NO: 315, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 331, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 349, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 369, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 387, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 401, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 417, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 427, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 437, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 445, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 455, or the amino acid sequence set forth in SEQ ID (29) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (30) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (31) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (32) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (33) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (34) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (35) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (36) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 537, or a variant thereof; (37) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 557, or a variant thereof; (38) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 577, or a variant thereof; (39) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 597, or a variant thereof; and / or acid sequence set forth in SEQ ID NO: 465, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 475, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 484, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 493, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 503, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 513, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 519, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 529, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 549, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 569, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 589, or the amino acid sequence set forth in SEQ ID (40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

[0023] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof; (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof; (8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof; (10) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 179, or a variant thereof; (11) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 215, or a variant thereof; (12) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 251, or a variant thereof; (13) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 287, or a variant thereof; (14) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 304, or a variant thereof; (15) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 323, or a variant thereof; (16) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 357, or a variant thereof; (17) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 391, or a variant thereof; (18) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (19) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; (20) a HCVR that comprises the amino a variant thereof; and a LCVR that comprises NO: 409, or a variant thereof; acid sequence set forth in SEQ ID NO: 173, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 207, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 245, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 279, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 297, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 315, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 349, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 387, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 417, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 427, or the amino acid sequence set forth in SEQ ID acid sequence set forth in SEQ ID NO: 437, or the amino acid sequence set forth in SEQ ID (21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; (27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or 28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0024] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or (7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0025] In some embodiments, the antigen-binding protein comprises: (1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof; (2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof; (3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof; (4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof; (5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and / or (6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

[0026] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof; (37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof; (38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof; (39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and / or (40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof.

[0027] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof; (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof; (8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof; (10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof; (11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof; (12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof; (13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof; (14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof; (15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof; (16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof; (17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof; (18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; (27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and / or (28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

[0028] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and / or (7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

[0029] In some embodiments, the antigen-binding protein comprises: (1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof; (2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof; (3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof; (4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof; (5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and / or (6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

[0030] In some embodiments, the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%.

[0031] In some embodiments, the antigen binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%.

[0032] In another aspect, provided herein is an antigen-binding protein that binds to the same epitope on p75NTR as an antibody comprising an HCVR / LCVR amino acid sequence pair as set forth in Table 1-1.

[0033] In a further aspect, provided herein is an antigen-binding protein that competes for binding to p75NTR with an antibody comprising an HCVR / LCVR amino acid sequence pair as set forth in Table 1-1.

[0034] In some embodiments, the antigen-binding protein comprises an antibody or antigenbinding fragment thereof.

[0035] In some embodiments, the antigen-binding protein is selected from a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody or biding fragment thereof, bi-specific T-cell engager (BiTE), trispecific antibody, or chemically modified derivatives thereof.

[0036] In one embodiment, the antigen-binding protein comprises a fragment antigen-binding region (Fab).

[0037] In one embodiment, the antigen-binding protein comprises a single chain fragment variable (scFv).

[0038] In one embodiment, the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: HCVR-LCVR.

[0039] In one embodiment, the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: LCVR-HCVR.

[0040] In some embodiments, the variable regions in the scFv are connected by a linker.

[0041] In one embodiment, the linker is a peptide linker.

[0042] In one embodiment, the peptide linker is -(GGGGS)n- (SEQ ID NO: 668), wherein n is any integral selected from 1-10.

[0043] In some embodiments, the antigen-binding protein binds to human p75NTR.

[0044] In one embodiment, the antigen-binding protein binds to human p75NTR with a KD of about 1X1 O’9 M or a stronger affinity.

[0045] In another aspect, provided herein is an isolated polynucleotide encoding the antigenbinding protein as described herein.

[0046] In a further aspect, provided herein is a vector comprising the isolated polynucleotide as described herein.

[0047] In a further aspect, provided herein is a host cell comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein or the vector as described herein.

[0048] In one embodiment, the host cell is a Chinese hamster ovary (CHO) cell.

[0049] In another aspect, provided herein is a protein-drug conjugate comprising an antigenbinding protein that binds to p75 neurotrophin receptor (p75NTR) and is conjugated to a molecular cargo.

[0050] In some embodiments, the antigen-binding protein of the protein-drug conjugate comprises the antigen-binding protein as described herein.

[0051] In one embodiment, the antigen-binding protein and the molecular cargo are conjugated via a linker.

[0052] In some embodiments, the molecular cargo comprises a polynucleotide molecule, a polypeptide molecule, a carrier, or a small molecule.

[0053] In one embodiment, the molecular cargo comprises a polynucleotide molecule.

[0054] In some embodiments, the polynucleotide molecule is an interfering nucleic acid molecule, a guide RNA, a ribozyme, an aptamer, a mixmer, a multimer, or an mRNA.

[0055] In one embodiment, the interfering nucleic acid molecule is an siRNA, an shRNA, a miRNA, an antisense oligonucleotide, or a gapmer.

[0056] In some embodiments, the interfering nucleic acid molecule is an siRNA.

[0057] In one embodiment, the siRNA comprises a sense strand of 21 nucleotides in length.

[0058] In one embodiment, the siRNA comprises an antisense strand of 23 nucleotides in length.

[0059] In some embodiments, the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 5’ end of the sense strand.

[0060] In some embodiments, the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 3’ and / or 5’ ends of the antisense strand.

[0061] In one embodiment, the interfering nucleic acid molecule is an antisense oligonucleotide.

[0062] In one embodiment, the polynucleotide molecule is a guide RNA.

[0063] In some embodiments, the polynucleotide molecule targets a gene or gene product associated with pain, itch, or a neurological disease or disorder.

[0064] In some embodiments, the gene or gene product associated with pain, itch, or a neurological disease or disorder is voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Nav1.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TRKC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 3 (ASIC3), transient receptor potential vaniIloid 1 (TRPV1), transient receptor potential vanilloid 4 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily M, members (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZO1), piezo type mechanosensitive ion channel component 2 (PIEZO2), enkephalin, RET protooncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor alpha (IL6Ra), glycoprotein 130 (gp130), FXYD domain containing ion transport regulator 2 (FXYD2), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), or interleukin 6 (IL6).

[0065] In some embodiments, the polynucleotide molecule comprises one or more modified nucleotides.

[0066] In some embodiments, the molecular cargo comprises a polypeptide molecule.

[0067] In some embodiments, the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75NTR.

[0068] In some embodiments, the polypeptide molecule is associated with pain, itch, or a neurological disease or disorder.

[0069] In some embodiments, the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling.

[0070] In some embodiments, the protein-drug conjugate is for use in treating or preventing pain, itch, ora neurological disease or disorder.

[0071] In some embodiments, the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS).

[0072] In one embodiment, the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia.

[0073] In one embodiment, the itch is chronic itch.

[0074] In some embodiments, the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer.

[0075] In one embodiment, the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

[0076] In one embodiment, the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema.

[0077] In one embodiment, the neurological cancer is a brain cancer or a peripheral nerve cancer.

[0078] In one embodiment, the pain, itch, or neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell or a trigeminal ganglion cell, or a population thereof.

[0079] In some embodiments, the molecular cargo comprises a carrier.

[0080] In some embodiments, the carrier is a lipid-based carrier.

[0081] In some embodiments, the lipid-based carrier is a lipid nanoparticle (LNP), a liposome, a lipidoid, ora lipoplex.

[0082] In one embodiment, the lipid-based carrier is a LNP.

[0083] In some embodiments, the LNP further comprises a polynucleotide molecule and / or a polypeptide molecule.

[0084] In some embodiments, the LNP comprises one or more components of a gene editing system.

[0085] In some embodiments, the LNP comprises: (a) a Cas nuclease, or a nucleic acid encoding the Cas nuclease, and / or (b) a guide RNA, or one or more DNAs encoding the guide RNA.

[0086] In one embodiment, the Cas nuclease is a Cas9 protein.

[0087] In some embodiments, the Cas9 protein is derived from a Streptococcus pyogenes Cas9 protein, a Staphylococcus aureus Cas9 protein, a Campylobacter jejuni Cas9 protein, a Streptococcus thermophilus Cas9 protein, or a Neisseria meningitidis Cas9 protein.

[0088] In some embodiments, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell.

[0089] In one embodiment, the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell.

[0090] In one embodiment, the nucleic acid encoding the Cas nuclease is an mRNA.

[0091] In one embodiment, the guide RNA is a single guide RNA (sgRNA).

[0092] In some embodiments, the LNP comprises a zinc finger nuclease (ZFN), or a transcription activator-like effector nuclease (TALEN).

[0093] In some embodiments, the LNP comprises a cationic lipid, a neutral lipid, a helper lipid, a stealth lipid, or any combination thereof.

[0094] In one embodiment, the neutral lipid is distearoylphosphatidylcholine (DSPC).

[0095] In one embodiment, the helper lipid is cholesterol.

[0096] In one embodiment, the stealth lipid is PEG2k-DMG.

[0097] In another aspect, provided herein is a pharmaceutical composition comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein and a pharmaceutically acceptable carrier.

[0098] In a further aspect, provided herein is a composition or kit comprising the antigenbinding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein or pharmaceutical composition as described herein and a further therapeutic agent.

[0099] In another aspect, provided herein is a complex comprising the antigen-binding protein as described herein or the protein-drug conjugate as described herein bound to a human p75 neurotrophin receptor (p75NTR) polypeptide.

[00100] In a further aspect, provided herein is a method for making the antigen-binding protein as described herein, comprising culturing a host cell comprising a polynucleotide that encodes the antigen-binding protein in a culture medium under conditions favorable to expression of the antigen-binding protein.

[00101] In some embodiments, the method for making the antigen-binding protein as described herein comprises the steps: (a) introducing said polynucleotide into a host cell; (b) culturing the host cell under conditions favorable to expression of the antigenbinding protein; (c) optionally, isolating the antigen-binding protein from the culture medium and / or host cell; and (d) optionally, conjugating the antigen-binding protein to a molecular cargo.

[00102] In another aspect, provided herein is an antigen-binding protein which is produced by or obtainable by the method as described herein.

[00103] In a further aspect, provided herein is a method for making a protein-drug conjugate as described herein comprising: (a) contacting the antigen-binding protein, with the molecular cargo under the conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and (b) optionally, isolating the protein-drug conjugate produced in step (a).

[00104] In another aspect, provided herein is a method for making a protein-drug conjugate as described herein, wherein the molecular cargo comprises a polypeptide molecule, comprising: (a) culturing a host cell comprising a polynucleotide encoding the protein-drug conjugate under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a).

[00105] In a further aspect, provided herein is a protein-drug conjugate which is produced by or obtainable by the method as described herein.

[00106] In another aspect, provided herein is a vessel or injection device comprising the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein.

[00107] In a further aspect, provided herein is a method for administering the antigenbinding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein to a subject comprising introducing the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate into the body of the subject.

[00108] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration.

[00109] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

[00110] In one embodiment, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

[00111] In another aspect, provided herein is a method for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject comprising administering to the subject the protein-drug conjugate as described herein, or the pharmaceutical composition as described herein.

[00112] In some embodiments, the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, or eye.

[00113] In one embodiment, the tissue is brain or spinal cord.

[00114] In one embodiment, the cell type is a sensory neuron.

[00115] In one embodiment, the cell type is a dorsal root ganglion cell or a trigeminal ganglion cell.

[00116] In some embodiments, the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration.

[00117] In some embodiments, the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

[00118] In one embodiment, the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

[00119] In one embodiment, the protein-drug conjugate is administered into the body of the subject via subcutaneous administration.

[00120] In one embodiment, the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration.

[00121] In a further aspect, provided herein is a method for treating or preventing pain, itch, or a neurological disease or disorder in a subject in need thereof comprising administering to the subject an effective amount of the antigen-binding protein as described herein, the isolated polynucleotide as described herein, the vector as described herein, or the protein-drug conjugate as described herein, or the pharmaceutical composition as described herein.

[00122] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered via subcutaneous, intramuscular, or intravenous administration.

[00123] In some embodiments, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

[00124] In one embodiment, the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

[00125] In some embodiments, the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, postherpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS).

[00126] In one embodiment, the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia.

[00127] In one embodiment, the itch is chronic itch.

[00128] In some embodiments, the neurological disease or disorder is a neurodegenerative disease, a neurodevelopmental disease, a chronic neuropathic pain, a physical injury, a neuropsychiatric disease, or a neurological cancer.

[00129] In one embodiment, the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

[00130] In one embodiment, the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema.

[00131] In one embodiment, the neurological cancer is a brain cancer or a peripheral nerve cancer.

[00132] In some embodiments, the pain, itch, or a neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell, a trigeminal ganglion cell, or a population thereof.

[00133] In some embodiments, the method as described herein further comprises administering an additional treatment to the subject.

[00134] In some embodiments, the additional treatment comprises administering a nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, a local anesthetic, capsaicin, a Cox-2 inhibitor, an antidepressant, an anti-seizure medication, an anti-epileptic medication, 59 an opioid, a steroid, an anticonvulsant, a muscle relaxant, a triptan, dihydroergotamine, Lasmiditan, a calcitonin gene-related peptides antagonist, an anti-nausea drug, a beta blocker, a calcium channel blocker, a serotonin and norepinephrine reuptake inhibitor (SNRI), onabotulinumtoxinA, or a benzodiazepine, or a combination thereof BRIEF DESCRIPTION OF THE FIGURES

[00135] Fig. 1 shows that anti-p75NTR antibody is internalized in ex vivo dorsal root ganglion (DRG) tissue. Live, time-lapse confocal imaging of DRGs grown ex vivo. Alexa 647 conjugated antibodies were applied at t=0, maximum projections of 3 confocal optical slices 10 pm apart are shown. Axons are labeled within 5 minutes of addition of fluorescently conjugated anti-p75NTR antibody to the culture media. Internalization into neuronal cell bodies is seen 1-4 hours post antibody addition.

[00136] Figs. 2A-2B show that anti-p75NTR antibody is internalized in ex vivo DRG tissue. Live, time-lapse confocal imaging of DRGs grown ex vivo. Alexa 647 conjugated antibodies were applied at t=0, maximum projections of 3 confocal optical slices 10 pm apart are shown. Axons are labeled within 5 minutes of addition of fluorescently conjugated anti-p75NTR antibody to the culture media. Internalization into neuronal cell bodies is seen 1-4 hours post antibody addition.

[00137] Figs. 3A-3F show that anti-p75NTR antibody internalizes in DRGs following intraplantar injection. Maximum projection of confocal Z stack images of whole DRGs harvested 5 days post injection of fluorescently conjugated antibody into the hind foot pad. Lumbar DRG ipsilateral to intraplantar injection of anti-Fel D1 (Fig. 3A), or anti-p75NTR REGN14155 (Fig. 3B), or anti-p75NTR REGN14187 (Fig. 3C). Lumbar DRG contralateral to intraplantar injection of anti-Fel D1 (Fig. 3D), or anti-p75NTR REGN14155 (Fig. 3E), or anti-p75NTR REGN14187. CT-B labels DRG neurons on the ipsilateral side of injection (Figs. SA-30), but not the contralateral side (Figs. 3D-3F). Anti-p75NTR antibody shows uptake in DRGs on both sides. CT-B, Cholera Toxin subunit B - Alexa 488 (Fig. 3F).

[00138] Figs. 4A-4C show that anti-p75NTR antibody internalizes in trigeminal ganglion (TG) following intraplantar injection. Maximum projection of confocal Z stack images of whole trigeminal ganglia harvested 5 days post injection of fluorescently conjugated antibody into the hind foot pad. Transmitted light and fluorescent image of trigeminal ganglion from: intraplantar injection of anti-Fel D1 (Fig. 4A); intraplantar injection of anti-p75NTR REGN14155 (Fig. 4B); intraplantar injection of anti-p75NTR REGN14187 (Fig. 4C).

[00139] Figs. 5A-5F show that anti-p75NTR antibody internalizes in DRGs and TG following intramuscular injection. Maximum projection of confocal Z stack images of whole DRGs harvested 5 days post injection of fluorescently conjugated antibody into the gastrocnemius muscle. Lumbar DRG ipsilateral to intramuscular injection of anti-Fel D1 (Fig. 5A). Lumbar DRG ipsilateral to intramuscular injection of anti-p75NTR REGN14187 (Fig. 5B). Lumbar DRG contralateral to intramuscular injection of anti-Fel D1 (Fig. 5C). Lumbar DRG contralateral to intramuscular injection of anti-p75NTR REGN14187 (Fig. 5D). Trigeminal ganglia from mouse injected with anti-Fel D1 in gastrocnemius muscle (Fig. 5E). Trigeminal ganglia from mouse injected with anti-p75NTR REGN14187 in gastrocnemius muscle (Fig. 5F). CT-B labels DRG neurons on the ipsilateral side of injection (Figs. 5A-5B), but not the contralateral side (Figs. 5C-5D) orTG (Figs. 5E-5F). Anti-p75NTR shows uptake in DRGs on both sides and uptake in trigeminal ganglion. CT-B, Cholera Toxin subunit B - Alexa 488.

[00140] Fig. 6 shows that anti-p75NTR antibody internalizes in all lumbar DRGs 3 days following subcutaneous injection. Fluorescent anti-p75NTR is detected in all lumbar DRGs 3 days post subcutaneous injection of 0.5 mg / kg fluorescently tagged antibody. A647 fluorescent image of lumbar DRGs overlayed onto transmitted light image of DRG is shown.

[00141] Figs. 7A-7B show that anti-p75NTR antibody internalizes in DRG neurons 3 days following subcutaneous injection. 20X confocal single slice images with 15x zoom allow visualization of intracellular distribution of fluorescently tagged anti-p75NTR REGN14187 in DRG neurons. Punctate, intracellular anti-p75NTR antibody is detected in neurons.

[00142] Figs. 8A-8C show that anti-p75NTR antibody internalizes in DRG neurons that express the marker of peripheral neurons, peripherin. Widefield, fluorescent images of DRG sections from mice that were injected with subcutaneously anti-p75NTR REGN14187, then stained with anti-peripherin to identify neurons.

[00143] Figs. 9A-9N shows that anti-p75NTR antibody internalizes in DRGs, TG, colon, eye and sympathetic ganglia 5 days following subcutaneous injection. Fluorescent anti-p75NTR antibody is detected in TG (Fig. 9B), cervical DRG (Fig. 9D), thoracic DRG (Fig. 9E) and lumbar DRGs (Fig. 9F) 5 days post subcutaneous injection of 0.7 mg / kg fluorescently tagged antibody. A647 fluorescent image of TG and DRGs overlayed onto transmitted light image of DRG is shown in Figs. 9A-9F. Fluorescent anti-p75NTR antibody is detected in colon (Fig. 9H). Higher magnification image of colon tissue shows that fluorescent anti-p75NTR 61 antibody internalizes in cells in the myenteric plexus (Fig. 91). Fluorescent anti-p75NTR antibody is detected in the eye (Fig. 9K). A647 fluorescent confocal image of colon or eye tissue is shown in Figs. 9G-9K. Fluorescent anti-p75NTR antibody is detected in sympathetic ganglia (Fig. 9M). A647 fluorescent widefield image of ventral side of the thoracic spinal cord and is shown in Figs. 9L-9M. In all tissue, subcutaneous injection of fluorescent anti-Fel D1 does not show fluorescent signal (Figs. 9A, 9C, 9G, 9J, and 9L). Co-labeling with neuron and glial markers in DRG confirmed that anti-p75NTR antibodies internalized in DRG neurons and not surrounding satellite glia (Fig. 9N).

[00144] Figs. 10A-10F show that that anti-p75NTR antibody has undetectable presence in cerebellum (Fig. 10A), hippocampus (Fig. 10B), liver (Fig. 10C) and spinal cord (Fig. 10F) following subcutaneous injection. Low detection of anti-p75NTR antibody is detected in choroid plexus (Fig. 10B), kidney (Fig. 10C) and heart (Fig. 10E) following subcutaneous injection. Confocal images of DAPI and A647 channels are shown.

[00145] Figs. 11A-11D show that anti-p75NTR antibody is detected in choroid plexus following subcutaneous injection. 10X confocal images of sagittal brain sections show anti-p75NTR antibody observed in choroid plexus (arrows) 5 days following subcutaneous injection, with little or no detection in other regions of the brain.

[00146] Figs. 12A-12D show that low levels of anti-p75NTR antibodies are detected in the brain following ICV injection. Fluorescent, 5x confocal images of sagittal brain sections demonstrate low accumulation of anti-p75NTR specific labeling in ventral and cortical regions (Fig. 12D). Both anti-Fel D1 (Fig. 12B) and anti-p75NTR antibodies (Fig. 12D) show accumulation in the ventricle, the site of injection.

[00147] Figs. 13A-13D show that Alexa-conjugated anti-p75 (Alexa-anti-p75) antibody is detected in sensory neurons in trigeminal ganglia that are ipsilateral (Fig. 13B), but not contralateral (Fig. 13D), to the injection site at sensory neuron terminals in the whisker pad, indicative of retrograde transport of the fluorescently conjugated antibodies along sensory neuron axons from the axon terminals to the sensory neuron cell body. Confocal images of DAPI staining of ipsilateral (Fig. 13A) and contralateral (Fig. 13C) trigeminal ganglia are also included.

[00148] Fig. 14 shows that intravenous delivery of anti-p75NTR antibody-Navi .7 siRNA conjugates improves Scn9a transcript reduction in trigeminal ganglia compared to isotype conjugated controls. Humanized Nav1.7 mice were injected twice intravenously (I.V.) with 50mg / kg of anti-p75NTR antibody-Navi .7 siRNA conjugate or isotype antibody conjugated 62 control. Trigeminal ganglia were collected 14 days following the first I.V. dose for quantitative PCR analysis. A reduction of approximately 30% of Navi .7 mRNA transcript is observed with anti-p75NTR antibody conjugation compared to isotype conjugated controls. n=3 mice per group.

[00149] Figs. 15A-15H show that internalization of fluorescent REGN anti-p75NTR into neurons was observed following intravenous injection of REGN19516 in the trigeminal ganglia (Fig. 15D) and DRG (Fig. 15H). Intravenous injection of fluorescent isotype control antibody, REGN1945, did not demonstrate labeling in TG or DRGs (Figs. 15B, 15F). DETAILED DESCRIPTION OF THE INVENTION

[00150] The present disclosure provides antigen-binding proteins that specifically bind to p75 neurotrophin receptor (p75NTR), or an antigenic fragment thereof. The present disclosure further provides protein-drug conjugates comprising an antigen-binding protein that specifically binds to p75NTR, or an antigenic fragment thereof, and that is conjugated to a molecular cargo. Such conjugates are useful, for example, for delivery of the molecular cargo to various tissues, e.g., peripheral nervous system, autonomic nervous system (such as sympathetic / parasympathetic nervous system, e.g., sympathetic and / or parasympathetic ganglia), enteric nervous system (such as myenteric plexus), central nervous system (CNS) and eye tissues, and / or cells, e.g., sensory neurons (such as, but not limited to, dorsal root ganglion (DRG) cells and / or trigeminal ganglion (TG) cells), sympathetic neurons, parasympathetic neurons and enteric neurons, in the body. In some embodiments, conjugates described herein can be useful for delivery of a molecular cargo described herein to cells such as dermal fibers, celiac ganglion cells, Muller glia, Leydig cells, ionocytes, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and the like. The conjugates described herein have an ability to efficiently deliver molecular cargoes to the nervous system including the peripheral nervous system, brain and the spinal cord and, in particular, DRG cells (e.g., neurons) and TG cells (e.g., neurons) therein and thus, can be used for treatment of pain (e.g., chronic pain including peripheral chronic pain), itch (e.g., chronic itch) and neurological diseases and disorders such as neurodegenerative, neurodevelopmental and neuropsychiatric disorders. In some embodiments, the conjugates described herein have an ability to efficiently deliver molecular cargoes to peptidergic and non-peptidergic sensory neurons (peripherin) in DRG. In some embodiments, anti-p75NTR can be taken up in a high percentage of DRG and / or TG cells (e.g., neurons) efficiently, with little uptake in peripheral tissues and brain.

[00151] In accordance with the present disclosure there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Second Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (herein "Sambrook, et al., 1989"); DNA Cloning: A Practical Approach, Volumes I and II (D. N. Glover ed. 1985); Oligonucleotide Synthesis (M. J. Gait ed. 1984); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins eds. (1985)); Transcription And Translation (B. D. Hames &S. J. Higgins, eds. (1984)); Animal Cell Culture (R. I. Freshney, ed. (1986)); Immobilized Cells And Enzymes (IRL Press, (1986)); B. Perbal, A Practical Guide To Molecular Cloning (1984); F. M. Ausubel, etal. (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1994).

[00152] A polynucleotide includes DNA and RNA. The present disclosure includes any polynucleotide described herein which is operably linked to a promoter or other expression control sequence.

[00153] The term “p75NTR” or “p75NTR” refers to p75 neurotrophin receptor. The p75 neurotrophin receptor (p75NTR) belongs to the tumor necrosis factor receptor superfamily (TNFRSF). p75NTR receptors expressed at axon terminals at the periphery are known to transport retrogradely to the soma, delivering survival, apoptosis and differentiation signals to the cell body. Rabies virus binds p75NTR receptors and hijacks retrograde transport machinery to infect neurons. In the presence of TrkA, p75NTR potentiates NGF signaling and increases survival and differentiation. In the absence of TrkA, NGF binding to p75NTR promotes apoptosis. p75NTR expression is increased in a number of pathological conditions such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), and ischemia. In the peripheral nervous system (PNS), p75NTR can be found, e.g., in sympathetic and sensory neurons (Qin et al., Journal of Neuroscience Research, 98(10), 1987-1998 (2000); Yamamoto et al., Neurochem Res 21, 929-938 (1996); each is incorporated herein by reference in its entirety), and in subsets of parasympathetic neurons and some enteric neurons. In non-neuronal tissue, p75NTR can be found in mesenchymal cells within several organs / structures, limb, maxillary pad, tooth, lung, muscle, testis, retina, pituitary, hair follicles, salivary glands, perivascular cells and meninges.

[00154] In an embodiment, an exemplary human p75NTR protein (NCBI accession number NP_002498.1) comprises the amino acid sequence: MGAGATGRAMDGPRLLLLLLLGVSLGGAKEACPTGLYTHSGECCKACNLGEGVAQPCGA NQTVCEPCLDSVTFSDVVSATEPCKPCTECVGLQSMSAPCVEADDAVCRCAYGYYQDET TGRCEACRVCEAGSGLVFSCQDKQNTVCEECPDGTYSDEANHVDPCLPCTVCEDTERQL RECTRWADAECEEIPGRWITRSTPPEGSDSTAPSTQEPEAPPEQDLIASTVAGVVTTVMG SSQPVVTRGTTDNLIPVYCSILAAVVVGLVAYIAFKRWNSCKQNKQGANSRPVNQTPPPEG EKLHSDSGISVDSQSLHDQQPHTQTASGQALKGDGGLYSSLPPAKREEVEKLLNGSAGDT WRHLAGELGYQPEHIDSFTHEACPVRALLASWATQDSATLDALLAALRRIQRADLVESLCS ESTATSPV (SEQ ID NO: 669).

[00155] In some embodiments, a human p75NTR protein described herein may be encoded by the nucleotide sequence of: ATGGGGGCAGGTGCCACCGGCCGCGCCATGGACGGGCCGCGCCTGCTGCTGTTGCT GCTTCTGGGGGTGTCCCTTGGAGGTGCCAAGGAGGCATGCCCCACAGGCCTGTACAC ACACAGCGGTGAGTGCTGCAAAGCCTGCAACCTGGGCGAGGGTGTGGCCCAGCCTT GTGGAGCCAACCAGACCGTGTGTGAGCCCTGCCTGGACAGCGTGACGTTCTCCGACG TGGTGAGCGCGACCGAGCCGTGCAAGCCGTGCACCGAGTGCGTGGGGCTCCAGAGC ATGTCGGCGCCGTGCGTGGAGGCCGACGACGCCGTGTGCCGCTGCGCCTACGGCTA CTACCAGGATGAGACGACTGGGCGCTGCGAGGCGTGCCGCGTGTGCGAGGCGGGCT CGGGCCTCGTGTTCTCCTGCCAGGACAAGCAGAACACCGTGTGCGAGGAGTGCCCCG ACGGCACGTATTCCGACGAGGCCAACCACGTGGACCCGTGCCTGCCCTGCACCGTGT GCGAGGACACCGAGCGCCAGCTCCGCGAGTGCACACGCTGGGCCGACGCCGAGTGC GAGGAGATCCCTGGCCGTTGGATTACACGGTCCACACCCCCAGAGGGCTCGGACAGC ACAGCCCCCAGCACCCAGGAGCCTGAGGCACCTCCAGAACAAGACCTCATAGCCAGC ACGGTGGCAGGTGTGGTGACCACAGTGATGGGCAGCTCCCAGCCCGTGGTGACCCG AGGCACCACCGACAACCTCATCCCTGTCTATTGCTCCATCCTGGCTGCTGTGGTTGTG GGCCTTGTGGCCTACATAGCCTTCAAGAGGTGGAACAGCTGCAAGCAGAACAAGCAA GGAGCCAACAGCCGGCCAGTGAACCAGACGCCCCCACCAGAGGGAGAAAAACTCCA CAGCGACAGTGGCATCTCCGTGGACAGCCAGAGCCTGCATGACCAGCAGCCCCACAC GCAGACAGCCTCGGGCCAGGCCCTCAAGGGTGACGGAGGCCTCTACAGCAGCCTGC CCCCAGCCAAGCGGGAGGAGGTGGAGAAGCTTCTCAACGGCTCTGCGGGGGACACC TGGCGGCACCTGGCGGGCGAGCTGGGCTACCAGCCCGAGCACATAGACTCCTTTACC CATGAGGCCTGCCCCGTTCGCGCCCTGCTTGCAAGCTGGGCCACCCAGGACAGCGC CACACTGGACGCCCTCCTGGCCGCCCTGCGCCGCATCCAGCGAGCCGACCTCGTGG AGAGTCTGTGCAGTGAGTCCACTGCCACATCCCCGGTG (SEQ ID NO: 670). p75NTR Binding Proteins and Protein-Drug Conjugates

[00156] In one aspect, the present disclosure provides antigen-binding proteins that bind specifically to p75NTR.

[00157] An antigen-binding protein that specifically binds to p75NTR may bind at about 25°C, to p75NTR or a fusion protein thereof, for example, a tag such as His6 (SEQ ID NO: 619) and / or myc fused to e.g., human p75NTR or monkey p75NTR, e.g., in a surface plasmon resonance assay, with a KD of about 1x1 O'9 M or a stronger affinity. Such an antigen-binding protein may be referred to as “anti-p75NTR”.

[00158] In some embodiments, the antigen-binding protein that specifically binds to p75NTR may comprise an antibody, or an antigen-binding fragment of an antibody, such as a fragment antigen-binding region (Fab) or single chain fragment variable (scFv).

[00159] The present disclosure further provides p75NTR binding protein-drug conjugates. A p75NTR binding protein-drug conjugate may comprise an optional signal peptide, connected to an antigen-binding protein (e.g., an antibody or an antigen-binding fragment of an antibody such as a fragment antigen-binding region (Fab) or single chain fragment variable (scFv)) that binds specifically to p75NTR, such as human p75NTR, and that is conjugated (optionally by a linker) to molecular cargo. The p75NTR binding protein-drug conjugates described herein can deliver the conjugated molecular cargo to a desired tissue (e.g., nervous tissue) and / or desired cell type (e.g., sensory neurons (such as, but not limited to, dorsal root ganglion cells and / or trigeminal ganglion cells)) in the body. Non-limiting examples of cell types to which a p75NTR binding protein-drug conjugate described herein can deliver a conjugated molecular cargo include neurons, Muller glial cells, Leydig cells, ionocytes, dorsal root ganglion (DRG) cells, trigeminal ganglion cells, sympathetic ganglion cells, dermal fiber cells, retinal cells, myenteric plexus cells, celiac ganglion cells, dendritic cells, Schwann cells, salivary gland cells, retinal bipolar neurons, basal respiratory cells, basal squamous epithelial cells, and oligodendrocytes.

[00160] The term "conjugate" means a body in which two substances are linked covalently, or non-covalently. The term "covalently linked" refers to a characteristic of at least two molecules being linked together by way of one or more covalent bond(s). In various embodiments, two molecules can be covalently linked together by a single bond, e.g., a 66 disulfide bridge or a disulfide bond, that operates as a linker between the molecules. In some embodiments, two or more molecules may be covalently linked together by way of a molecule that operates as a linker that joins the at least two molecules together via multiple covalent bonds. In certain embodiments, a linker can be a cleavable linker or a non-cleavable linker. In the conjugate, the two substances may be linked directly or may be linked via a linker. In the present disclosure, one of the two substances is an antigen-binding protein, e.g., an antibody or antigen-binding fragment thereof, and the other is a drug (e.g., a polynucleotide, a polypeptide, or a liposome or LNP disclosed herein). In the present disclosure, the linker may be a cleavable linker or may be a non-cleavable linker. In some embodiments, two polypeptide molecules that are covalently linked, either directly or indirectly (e.g., by a linker), may be expressed from one single polynucleotide molecule.

[00161] As used herein, the term "antibody-drug conjugate" or “ADC” means a conjugate of an antibody or antigen-binding fragment thereof with a drug (e.g., a polynucleotide, a polypeptide, or a liposome or LNP disclosed herein). The affinity to an antigen is imparted to a drug by linking an antibody or antigen-binding fragment thereof with the drug (e.g., a polynucleotide, or a liposome or LNP disclosed herein), thereby increasing the efficiency of delivering the drug to a target site in vivo. “Antibody-drug conjugates” or “ADCs” as used herein also encompass fusion proteins wherein the antibody or antigenbinding fragment thereof is fused with another polypeptide molecule.

[00162] The present disclosure includes antibodies and antigen-binding fragments thereof, such as Fabs and scFvs, that bind specifically to p75NTR, such as the human p75NTR.

[00163] The term "antibody", as used herein, refers to immunoglobulin molecules comprising four polypeptide chains, two heavy chains (HCs) and two light chains (LCs), interconnected by disulfide bonds (e.g., IgG). In an embodiment, each antibody heavy chain (HC) comprises a heavy chain variable region (“HCVR” or “VH”) (e.g., SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261, 279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589, 609 or a variant thereof) and a heavy chain constant region; and each antibody light chain (LC) comprises a light chain variable region (“LCVR or “VL”) (e.g., SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251, 269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, 597 or a variant thereof) and a light chain constant region (CL). The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL comprises three CDRs and four FRs.

[00164] In an embodiment, the assignment of amino acids to each framework or CDR domain in an immunoglobulin is in accordance with the definitions of Sequences of Proteins of Immunological Interest, Kabat et al.; National Institutes of Health, Bethesda, Md.; 5th ed.; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chern. 32:1-75; Kabat et al., (1977) J. Biol. Chern. 252:6609-6616; Chothia, etal., (1987) J Mol. Biol. 196:901-917 or Chothia, et al., (1989) Nature 342: 878-883. Thus, the present disclosure includes antibodies and antigen-binding fragments including the CDRs of a VH and the CDRs of a VL, which VH and VL comprise amino acid sequences as set forth herein (see e.g., sequences of Table 1-1, or a variant thereof), wherein the CDRs are as defined according to Kabat and / or Chothia.

[00165] An p75NTR binding protein described herein may be an antigen-binding fragment of an antibody which optionally may be conjugated to a molecular cargo. The terms "antigen-binding portion" or "antigen-binding fragment" of an antibody, as used herein, refers to an immunoglobulin molecule that binds antigen but that does not include all of the sequences of a full antibody (preferably, the full antibody is an IgG). Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; and (vi) dAb fragments; consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3-CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies and small modular immunopharmaceuticals (SMIPs), are also encompassed within the expression "antigenbinding fragment," as used herein.

[00166] As mentioned, an p75NTR binding protein described herein may be an scFv which optionally may be conjugated to a molecular cargo. An scFv (single chain fragment variable) has variable regions of heavy (Vh) and light (Vl) domains (in either order), which, preferably, are joined together by a flexible linker (e.g., peptide linker). The length of the flexible linker used to link both of the V regions may be important for yielding the correct folding of the polypeptide chain. Previously, it has been estimated that the peptide linker must span 3.5 nm (35 A) between the carboxy terminus of the variable domain and the amino terminus of the other domain without affecting the ability of the domains to fold and form an 68 intact antigen-binding site (Huston et al., Protein engineering of single-chain Fv analogs and fusion proteins. Methods in Enzymology. 1991;203:46-88). In an embodiment, the linker comprises an amino acid sequence of such length to separate the variable domains by about 3.5 nm.

[00167] In some embodiments, an antigen-binding protein that specifically binds to p75NTR comprises a heavy chain variable region (HCVR or VH) and / or a light chain variable region (LCVR or Vl).

[00168] In an embodiment, an antigen-binding protein that specifically binds to p75NTR comprises an anti-p75NTR scFv comprising the arrangement of variable regions as follows LCVR-HCVR or HCVR-LCVR, wherein the HCVR and LCVR are optionally connected by a linker.

[00169] In some embodiments, a p75NTR binding protein-drug conjugate comprises a heavy chain variable region (HCVR or VH) and / or a light chain variable region (LCVR or VL).

[00170] In an embodiment, a p75NTR binding protein-drug conjugate includes an anti-p75NTR scFv comprising the arrangement of variable regions as follows LCVR-HCVR or HCVR-LCVR, wherein the HCVR and LCVR are optionally connected by a linker and the scFv is connected, optionally by a linker, to a molecular cargo (e.g., LCVR-(Gly4Ser)3(SEQ ID NO: 623)-HCVR-molecular cargo; or LCVR-(Gly4Ser)s (SEQ ID NO: 623)-HCVR-molecular cargo).

[00171] In some embodiments, an p75NTR binding protein described herein comprises a monovalent or “one-armed” antibody. The monovalent or "one-armed" antibodies as used herein refer to immunoglobulin proteins comprising a single variable domain. For example, the one-armed antibody may comprise a single variable domain within a Fab wherein the Fab is linked to at least one Fc fragment. In certain embodiments, the one-armed antibody comprises: (i) a heavy chain comprising a heavy chain constant region and a heavy chain variable region, (ii) a light chain comprising a light chain constant region and a light chain variable region, and (iii) a polypeptide comprising a Fc fragment or a truncated heavy chain. In certain embodiments, the Fc fragment or a truncated heavy chain comprised in the separate polypeptide is a "dummy Fc," which refers to an Fc fragment that is not linked to an antigen binding domain. The one-armed antibodies of the present disclosure may comprise any of the HCVR / LCVR pairs or CDR amino acid sequences as set forth in Table 1 -1 herein. One-armed antibodies comprising a full-length heavy chain, a full-length light chain and an additional Fc domain polypeptide can be constructed using standard methodologies (see, 69 e.g., WO2010151792, which is incorporated herein by reference in its entirety), wherein the heavy chain constant region differs from the Fc domain polypeptide by at least two amino acids (e.g., H95R and Y96F according to the IMGT exon numbering system; or H435R and Y436F according to the EU numbering system). Such modifications are useful in purification of the monovalent antibodies (see WO2010151792).

[00172] An antigen-binding fragment of an antibody will, in an embodiment, comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR, which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VH domain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH - VH, Vh - VL or VL - VL dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH and / or VL domain which are bound non-covalently.

[00173] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Nonlimiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody described herein include: (i) VH -CH1; (ii) VH -CH2; (iii) VH -CH3; (iv) Vh-CH1-CH2; (v) Vh -CH1-CH2-CH3; (vi) VH -CH2-CH3; (vii) VH -CL; (viii) VL -CH1; (ix) VL -CH2; (x) VL -CH3; (xi) VL -CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL -CH2-CH3; and (xiv) VL -CL. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, which result in a flexible or semi-flexible linkage between adjacent variable and / or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody described herein may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and / or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)). The present disclosure includes an antigen-binding fragment of an antigen-binding protein such as an antibody set forth herein, for example, REGN14148; REGN14149;  REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155;  REGN14156; REGN14157;  REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163;  REGN14164; REGN14165; REGN14175; REGN14176;  REGN14177; REGN14178;  REGN14179; REGN14180; REGN14181; REGN14182;  REGN14183; REGN14184;  REGN14185; REGN14186; REGN14187; REGN14188;  REGN14189; REGN14190;  REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517.

[00174] Antigen-binding proteins (e.g., antibodies and antigen-binding fragments) may be monospecific or multispecific (e.g., bispecific). Multispecific antigen-binding proteins are discussed further herein. The present disclosure includes monospecific as well as multispecific (e.g., bispecific) antigen-binding fragments comprising one or more variable domains from an antigen-binding protein that is specifically set forth herein (e.g., REGN14148;  REGN14149; REGN14150;  REGN14151; REGN14152; REGN14153; REGN14154;  REGN14155; REGN14156;  REGN14157; REGN14158; REGN14159; REGN14160;  REGN14161; REGN14162;  REGN14163; REGN14164; REGN14165; REGN14175;  REGN14176; REGN14177;  REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183;  REGN14184; REGN14185; REGN14186; REGN14187;  REGN14188; REGN14189;  REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517).

[00175] The term “specifically binds” or “binds specifically”, or the like, means that an antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) forms a complex with an antigen that is relatively stable under physiologic conditions. Specific binding can be characterized by an equilibrium dissociation constant (KD) of about 1x1 O’6 M or less, e.g., 10'7M, 10'8M, 10'9M, 10'10M, 10'11M, or 10'12M (a smaller KD denotes a tighter binding). Methods for determining whether an antigen-binding protein (e.g., an antibody or antigenbinding fragment thereof) specifically binds to an antigen are known in the art and include, for example, equilibrium dialysis, surface plasmon resonance (e.g., BIACORE™), bio-layer interferometry assay (e.g., Octet® HTX biosensor), solution-affinity ELISA, and the like. In some embodiments, specific binding is measured in a surface plasmon resonance assay, e.g., at 25°C or 37°C. An antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that specifically binds an antigen from one species may or may not have cross-reactivity to other antigens, such as an orthologous antigen from another species. The present disclosure includes antigen-binding proteins that specifically bind to p75NTR protein (e.g., human p75NTR protein, mouse p75NTR protein, and / or cynomolgus monkey p75NTR protein). “Anti-p75NTR” refers to an antigen-binding protein (or other molecule), for example an antibody or antigen-binding fragment thereof, that binds specifically to p75NTR.

[00176] "Isolated" antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof), polypeptides, polynucleotides and vectors, are at least partially free of other biological molecules from the cells or cell culture from which they are produced. Such biological molecules include nucleic acids, proteins, other antibodies or antigen-binding fragments, lipids, carbohydrates, or other material such as cellular debris and growth medium. An isolated antigen-binding protein may further be at least partially free of expression system components such as biological molecules from a host cell or of the growth medium thereof. Generally, the term "isolated" is not intended to refer to a complete absence of such biological molecules (e.g., minor or insignificant amounts of impurity may remain) or to an absence of water, buffers, or salts or to components of a pharmaceutical formulation that includes the antigen-binding proteins (e.g., antibodies or antigen-binding fragments).

[00177] The present disclosure includes antigen-binding proteins, e.g., antibodies or antigen-binding fragments, that bind to the same epitope as an antigen-binding protein described herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153;  REGN14154; REGN14155;  REGN14156; REGN14157; REGN14158; REGN14159;  REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165;  REGN14175; REGN14176;  REGN14177; REGN14178; REGN14179; REGN14180;  REGN14181; REGN14182;  REGN14183; REGN14184; REGN14185; REGN14186;  REGN14187; REGN14188;  REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517).

[00178] An antigen is a molecule, such as a peptide (e.g., p75NTR or a fragment thereof (an antigenic fragment)), to which, for example, an antibody or antigen-binding fragment thereof binds. The specific region on an antigen that an antibody recognizes and binds to is called the epitope. Antigen-binding proteins (e.g., antibodies) described herein that specifically bind to such antigens are part of the present disclosure.

[00179] The term “epitope” refers to an antigenic determinant (e.g., on p75NTR) that interacts with a specific antigen-binding site of an antigen-binding protein, e.g., a variable region of an antibody, known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas on an antigen and may have different biological effects. The term “epitope” may also refer to a site on an antigen to which B and / or T cells respond and / or to a region of an antigen that is bound by an antibody. Epitopes may be defined as structural or functional. Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity of the interaction. Epitopes may be linear or conformational, that is, composed of non-linear amino acids. In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and / or specific charge characteristics. Epitopes to which antigenbinding proteins described herein bind may be included in fragments of p75NTR, for example the extracellular domain thereof. Antigen-binding proteins (e.g., antibodies) described herein that bind to such epitopes are part of the present disclosure.

[00180] Methods for determining the epitope of an antigen-binding protein, e.g., antibody or fragment or polypeptide, include alanine scanning mutational analysis, peptide blot analysis (Reineke (2004) Methods Mol. Biol. 248: 443-63), peptide cleavage analysis, crystallographic studies and NMR analysis. In addition, methods such as epitope excision, epitope extraction and chemical modification of antigens can be employed (Tomer (2000) Prot. Sci. 9: 487-496). Another method that can be used to identify the amino acids within a polypeptide with which an antigen-binding protein (e.g., antibody or fragment or polypeptide) interacts is hydrogen / deuterium exchange detected by mass spectrometry. See, e.g., Ehring (1999) Analytical Biochemistry 267: 252-259; Engen and Smith (2001) Anal. Chern. 73: 256A-265A.

[00181] The present disclosure includes antigen-binding proteins that compete for binding to p75NTR, e.g., an p75NTR epitope as discussed herein, with an antigen-binding protein described herein, e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152;  REGN14153; REGN14154;  REGN14155; REGN14156; REGN14157; REGN14158;  REGN14159; REGN14160;  REGN14161; REGN14162; REGN14163; REGN14164;  REGN14165; REGN14175;  REGN14176; REGN14177; REGN14178; REGN14179;  REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185;  REGN14186; REGN14187;  REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; orREGN19517. The term “competes” as used herein, refers to an antigen-binding protein (e.g., antibody or antigen-binding fragment thereof) that binds to an antigen (e.g., p75NTR) and inhibits or blocks the binding of another antigen-binding protein (e.g., antibody or antigen-binding fragment thereof) to the antigen. Unless otherwise stated, the term also includes competition between two antigen-binding proteins e.g., antibodies, in both orientations, i.e., a first antibody that binds antigen and blocks binding by a second antibody and vice versa. Thus, in an 73 embodiment, competition occurs in one such orientation. In certain embodiments, the first antigen-binding protein (e.g., antibody) and second antigen-binding protein (e.g., antibody) may bind to the same epitope. Alternatively, the first and second antigen-binding proteins (e.g., antibodies) may bind to different, but, for example, overlapping or non-overlapping epitopes, wherein binding of one inhibits or blocks the binding of the second antibody, e.g., via steric hindrance. Competition between antigen-binding proteins (e.g., antibodies) may be measured by methods known in the art, for example, by a real-time, label-free bio-layer interferometry assay. Also, binding competition between anti-p75NTR antigen-binding proteins (e.g., monoclonal antibodies (mAbs)) can be determined using a real time, label-free bio-layer interferometry assay on an Octet RED384 biosensor (Pall ForteBio Corp.).

[00182] Typically, an antibody or antigen-binding fragment described herein which is modified in some way retains the ability to specifically bind to p75NTR, e.g., retains at least 10% of its p75NTR binding activity (when compared to the parental antibody) when that activity is expressed on a molar basis. Preferably, an antibody or antigen-binding fragment described herein retains at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the p75NTR binding affinity as the parental antibody. It is also intended that an antibody or antigen-binding fragment described herein may include conservative or non-conservative amino acid substitutions (referred to as "conservative variants" or "function conserved variants" of the antibody) that do not substantially alter its biologic activity.

[00183] An p75NTR binding protein described herein may be a monoclonal antibody or an antigen-binding fragment of a monoclonal antibody which optionally may be conjugated to a molecular cargo. The present disclosure includes monoclonal p75NTR binding proteins, e.g., antibodies and antigen-binding fragments thereof (e.g., REGN14148; REGN14149; REGN14150;  REGN14151; REGN14152;  REGN14153; REGN14154; REGN14155; REGN14156;  REGN14157; REGN14158;  REGN14159; REGN14160; REGN14161; REGN14162;  REGN14163; REGN14164;  REGN14165; REGN14175; REGN14176; REGN14177;  REGN14178; REGN14179;  REGN14180; REGN14181; REGN14182; REGN14183;  REGN14184; REGN14185;  REGN14186; REGN14187; REGN14188; REGN14189;  REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517), as well as monoclonal compositions comprising a plurality of isolated monoclonal antigen-binding proteins. The term "monoclonal antibody" or “mAb”, as used herein, refers to a member of a population of substantially homogeneous antibodies, i.e., the antibody molecules comprising the population are identical in amino acid sequence except for possible naturally occurring mutations that may be present in minor amounts. A "plurality" of such monoclonal antibodies and fragments in a composition refers to a concentration of identical (i.e., as discussed above, in amino acid sequence except for possible naturally occurring mutations that may be present in minor amounts) antibodies and fragments which is above that which would normally occur in nature, e.g., in the blood of a host organism such as a mouse or a human.

[00184] In an embodiment, an p75NTR binding protein, e.g., antibody or antigen-binding fragment (which optionally may be conjugated to a molecular cargo) comprises a heavy chain constant domain, e.g., of the type IgA (e.g., lgA1 or lgA2), IgD, IgE, IgG (e.g., lgG1, lgG2, lgG3 and lgG4) or IgM. In an embodiment, an antigen-binding protein, e.g., antibody or antigen-binding fragment, comprises a light chain constant domain, e.g., of the type kappa or lambda. In an embodiment, a VH as set forth herein is linked to a human heavy chain constant domain (e.g., IgG) and a VL as set forth herein is linked to a human light chain constant domain (e.g., kappa). The present disclosure includes antigen-binding proteins comprising the variable domains set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153;  REGN14154; REGN14155; REGN14156; REGN14157;  REGN14158; REGN14159;  REGN14160; REGN14161; REGN14162; REGN14163;  REGN14164; REGN14165;  REGN14175; REGN14176; REGN14177; REGN14178;  REGN14179; REGN14180;  REGN14181; REGN14182; REGN14183; REGN14184;  REGN14185; REGN14186;  REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517), which are linked to a heavy and / or light chain constant domain, e.g., as set forth herein.

[00185] The present disclosure includes human p75NTR binding proteins which optionally may be conjugated to a molecular cargo. The term "human” antigen-binding protein, such as an antibody or antigen-binding fragment, as used herein, includes antibodies and fragments having human amino acid sequence; for example, variable and constant regions derived from human germline immunoglobulin sequences whether in a human cell or grafted into a non-human cell, e.g., a mouse cell. See e.g., U.S. Patent Nos. 8,502,018; 6,596,541 or 5,789,215. The anti-p75NTR human mAbs described herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody", as used 75 herein, is not intended to include mAbs in which CDR sequences derived from the germline of another mammalian species (e.g., mouse) have been grafted onto human FR sequences. The term includes antibodies recombinantly produced in a non-human mammal or in cells of a non-human mammal. The term is not intended to include natural antibodies directly isolated from a human subject. The present disclosure includes human antigen-binding proteins (e.g., antibodies or antigen-binding fragments thereof such as REGN14148; REGN14149; REGN14150;  REGN14151; REGN14152;  REGN14153; REGN14154; REGN14155; REGN14156;  REGN14157; REGN14158;  REGN14159; REGN14160; REGN14161; REGN14162;  REGN14163; REGN14164;  REGN14165; REGN14175; REGN14176; REGN14177;  REGN14178; REGN14179;  REGN14180; REGN14181; REGN14182; REGN14183;  REGN14184; REGN14185;  REGN14186; REGN14187; REGN14188; REGN14189;  REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517).

[00186] The present disclosure includes anti-p75NTR chimeric antigen-binding proteins, e.g., antibodies and antigen-binding fragments thereof (which optionally may be conjugated to a molecular cargo), and methods of use thereof. As used herein, a "chimeric antibody" is an antibody having the variable domain from a first antibody and the constant domain from a second antibody, where the first and second antibodies are from different species, (see e.g., US4816567; and Morrison et al., (1984) Proc. Natl. Acad. Sci. USA 81: 6851-6855). The present disclosure includes chimeric antibodies comprising the variable domains which are set forth herein (e.g., from REGN14148; REGN14149; REGN14150; REGN14151; REGN14152;  REGN14153; REGN14154;  REGN14155; REGN14156; REGN14157; REGN14158;  REGN14159; REGN14160;  REGN14161; REGN14162; REGN14163; REGN14164;  REGN14165; REGN14175;  REGN14176; REGN14177; REGN14178; REGN14179;  REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185;  REGN14186; REGN14187;  REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) and a non-human constant domain.

[00187] The term “recombinant” p75NTR binding proteins, such as antibodies or antigenbinding fragments thereof (which optionally may be conjugated to a molecular cargo), refers to such molecules created, expressed, isolated or obtained by technologies or methods known in the art as recombinant DNA technology which include, e.g., DNA splicing and transgenic expression. The term includes antibodies expressed in a non-human mammal (including transgenic non-human mammals, e.g., transgenic mice), or a cell (e.g., CHO cells) such as a cellular expression system or isolated from a recombinant combinatorial human antibody library. The present disclosure includes recombinant antigen-binding proteins, such as antibodies and antigen-binding fragments as set forth herein (e.g., REGN14148; REGN14149;  REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155;  REGN14156; REGN14157;  REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163;  REGN14164; REGN14165; REGN14175; REGN14176;  REGN14177; REGN14178;  REGN14179; REGN14180; REGN14181; REGN14182;  REGN14183; REGN14184;  REGN14185; REGN14186; REGN14187; REGN14188;  REGN14189; REGN14190;  REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517).

[00188] An antigen-binding fragment of an antibody will, in an embodiment, comprise less than a full antibody but still binds specifically to antigen, e.g., p75NTR, e.g., including at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one (e.g., 3) CDR(s), which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VH domain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH - VH, Vh - VL or VL - VL dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH and / or VL domain which are bound non-covalently.

[00189] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Nonlimiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody described herein include: (i) VH -CH1; (ii) VH -CH2; (iii) VH -CH3; (iv) Vh-CH1-CH2; (v) Vh -CH1-CH2-CH3; (vi) VH -CH2-CH3; (vii) VH -CL; (viii) VL -CH1; (ix) VL -CH2; (x) VL -CH3; (xi) VL -CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL -CH2-CH3; and (xiv) VL -CL. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids, which result in a flexible or semi-flexible linkage between adjacent variable and / or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody described herein may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and / or with one or more monomeric VH or VL domain (e.g., by disulfide bond(s)). The present disclosure includes an antigen-binding fragment of an antigen-binding protein such as an antibody set forth herein, for example, REGN14148; REGN14149;  REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155;  REGN14156; REGN14157;  REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163;  REGN14164; REGN14165; REGN14175; REGN14176;  REGN14177; REGN14178;  REGN14179; REGN14180; REGN14181; REGN14182;  REGN14183; REGN14184;  REGN14185; REGN14186; REGN14187; REGN14188;  REGN14189; REGN14190;  REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517.

[00190] Antigen-binding proteins (e.g., antibodies and antigen-binding fragments) may be monospecific or multi-specific (e.g., bispecific). Multispecific antigen-binding proteins are discussed further herein. The present disclosure includes monospecific as well as multispecific (e.g., bispecific) antigen-binding fragments comprising one or more variable domains from an antigen-binding protein that is specifically set forth herein (e.g., REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517).

[00191] A "variant" of a polypeptide, such as an immunoglobulin ( :hain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152; REGN14153; REGN14154; REGN14155; REGN14156; REGN14157; REGN14158; REGN14159; REGN14160; REGN14161; REGN14162; REGN14163; REGN14164; REGN14165; REGN14175; REGN14176; REGN14177; REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185; REGN14186; REGN14187; REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517 VH, VL, HC or LC or CDR thereof comprising the amino acid sequence specifically set forth herein), refers to a polypeptide comprising an amino acid sequence that is at least about 70-99.9% (e.g., at least 70, 72, 74, 78 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5 or 99.9%) identical or similar to a referenced amino acid sequence that is set forth herein (e.g., any of SEQ ID NOs: 2, 10, 18, 20, 22, 30, 38, 40, 42, 50, 54, 56, 58, 66, 74, 76, 78, 86, 94, 96, 98, 106, 112, 114, 116, 124, 132, 134, 136, 144, 151, 153, 155, 162, 169, 171, 173, 179, 185, 187, 189, 197, 203, 205, 207, 215, 223, 225, 227, 235, 241, 243, 245, 251, 257, 259, 261, 269, 275, 277, 279, 287, 293, 295, 297, 304, 311, 313, 315, 323, 327, 329, 331, 339, 345, 347, 349, 357, 365, 367, 369, 377, 383, 385, 387, 391, 397, 399, 401, 409, 413, 415, 417, 425, 427, 435, 437, 443, 445, 453, 455, 463, 465, 473, 475, 482, 484, 491, 493, 501, 503, 511, 513, 517, 519, 527, 529, 545, 547, 549, 565, 567, 569, 585, 587, 589, 605, 607, 609 or 617); when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences (e.g., expect threshold: 10; word size: 3; max matches in a query range: 0; BLOSUM 62 matrix; gap costs: existence 11, extension 1; conditional compositional score matrix adjustment) and / or comprising the amino acid sequence but having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations (e.g., point mutation, insertion, truncation, and / or deletion).

[00192] Moreover, a variant of a polypeptide may include a polypeptide such as an immunoglobulin chain (e.g., an REGN14148; REGN14149; REGN14150; REGN14151; REGN14152;  REGN14153; REGN14154;  REGN14155; REGN14156; REGN14157; REGN14158;  REGN14159; REGN14160;  REGN14161; REGN14162; REGN14163; REGN14164;  REGN14165; REGN14175;  REGN14176; REGN14177; REGN14178; REGN14179;  REGN14180; REGN14181; REGN14182; REGN14183; REGN14184; REGN14185;  REGN14186; REGN14187;  REGN14188; REGN14189; REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; orREGN19517 VH, VL, HC or LC or CDR thereof) which may include the amino acid sequence of the reference polypeptide whose amino acid sequence is specifically set forth herein but for one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations, e.g., one or more missense mutations (e.g., conservative substitutions), non-sense mutations, deletions, or insertions. See Table 1-1. For example, the present disclosure includes p75NTR binding proteins which include an immunoglobulin light chain (or Vl) variant comprising the amino acid sequence set forth in SEQ ID NO: 10 but having one or more of such mutations and / or an immunoglobulin heavy chain (or VH) variant comprising the amino acid sequence set forth in SEQ ID NO: 2 but having one or more of such mutations. In an embodiment, an p75NTR binding protein includes an immunoglobulin light chain variant comprising LCDR1, LCDR2 and LCDR3 wherein one or more (e.g., 1 or 2 or 3) of such CDRs has one or more of such mutations (e.g., conservative substitutions) and / or an immunoglobulin heavy chain variant comprising HCDR1, HCDR2 and HCDR3 wherein one or more (e.g., 1 or 2 or 3) of such CDRs has one or more of such mutations (e.g., conservative substitutions).

[00193] The following references relate to BLAST algorithms often used for sequence analysis: BLAST ALGORITHMS: Altschul et al. (2005) FEBS J. 272(20): 5101-5109; Altschul, S. F., et al., (1990) J. Mol. Biol. 215:403-410; Gish, W„ et al., (1993) Nature Genet. 3:266272; Madden, T. L„ et al., (1996) Meth. Enzymol. 266:131-141; Altschul, S. F„ et al., (1997) Nucleic Acids Res. 25:3389-3402; Zhang, J., etal., (1997) Genome Res. 7:649-656; Wootton, J. C., et al., (1993) Comput. Chern. 17:149-163; Hancock, J. M. et al., (1994) Comput. Appl. Biosci. 10:67-70; ALIGNMENT SCORING SYSTEMS: Dayhoff, M. 0., et al., "A model of evolutionary change in proteins." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3. M. O. Dayhoff (ed.), pp. 345-352, Natl. Biomed. Res. Found., Washington, D.C.; Schwartz, R. M., et al., "Matrices for detecting distant relationships." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3." M. O. Dayhoff (ed.), pp. 353-358, Natl. Biomed. Res. Found., Washington, D.C.; Altschul, S. F., (1991) J. Mol. Biol. 219:555-565; States, D. J., et al., (1991) Methods 3:66-70; Henikoff, S., et al., (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919; Altschul, S. F., et al., (1993) J. Mol. Evol. 36:290-300; ALIGNMENT STATISTICS: Karlin, S., etal., (1990) Proc. Natl. Acad. Sci. USA87:2264-2268; Karlin, S., et al., (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877; Dembo, A., et al., (1994) Ann. Prob. 22:2022-2039; and Altschul, S. F. "Evaluating the statistical significance of multiple distinct local alignments." in Theoretical and Computational Methods in Genome Research (S. Suhai, ed.), (1997) pp. 1-14, Plenum, N.Y.

[00194] A "conservatively modified variant" or a "conservative substitution", e.g., of an immunoglobulin chain set forth herein, refers to a variant wherein there is one or more substitutions of amino acids in a polypeptide with other amino acids having similar characteristics (e.g., charge, side-chain size, hydrophobicity / hydrophilicity, backbone conformation and rigidity, etc.). Such changes can frequently be made without significantly disrupting the biological activity of the antibody or fragment. Those of skill in this art recognize that, in general, single amino acid substitutions in non-essential regions of a polypeptide do not substantially alter biological activity (see, e.g., Watson et al. (1987) Molecular Biology of the Gene, The Benjamin / Cummings Pub. Co., p. 224 (4th Ed.)). In addition, substitutions of 80 structurally or functionally similar amino acids are less likely to significantly disrupt biological activity. The present disclosure includes p75NTR binding proteins comprising such conservatively modified variant immunoglobulin chains.

[00195] Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic-hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartate and glutamate, and 7) sulfur-containing side chains: cysteine and methionine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet etal. (1992) Science 256: 1443-45.

[00196] “REGN14148”; “REGN14149”; “REGN14150”; “REGN14151”; “REGN14152”; “REGN14153”; “REGN14154”; “REGN14155”; “REGN14156”; “REGN14157” “REGN14158”; “REGN14159”; “REGN14160”; “REGN14161”; “REGN14162” “REGN14163”; “REGN14164”; “REGN14165”; “REGN14175”; “REGN14176” “REGN14177”; “REGN14178”; “REGN14179”; “REGN14180”; “REGN14181” “REGN14182”; “REGN14183”; “REGN14184”; “REGN14185”; “REGN14186” “REGN14187”; “REGN14188”; “REGN14189”; “REGN14190”; “REGN14191” “REGN19513”; “REGN19514”; “REGN19515”; “REGN19516”; and “REGN19517” unless otherwise stated, refer to p75NTR binding proteins, e.g., antibodies and antigen-binding fragments thereof (including multispecific antigen-binding proteins), comprising an immunoglobulin heavy chain variable region (Vh) and an immunoglobulin light chain variable region (Vl) comprising the amino acid sequence pair specifically set forth in SEQ ID NOs: 2 &10; 22&30; 42 & 50; 58 & 66; 78 & 86; 98 & 106; 116 & 124; 136 & 144; 155 & 162; 173 & 179; 189 & 197; 207 & 215; 227 & 235; 245 & 251; 261 & 269; 279 & 287; 297 & 304; 315 & 323; 331 & 339; 349 & 357; 369 & 377; 387 & 391; 401 & 409; 417 & 409; 427 & 409; 437 & 409; 445 & 409; 455 & 409; 465 & 409; 475 & 409; 484 & 409; 493 & 409; 503 & 409; 513 & 409; 519 & 409; 529 & 537; 549 & 557; 569 & 577; 589 & 597; and 609 & 597 (or a variant of any of said sequences), respectively; or comprising an immunoglobulin heavy chain (HC) and an immunoglobulin light chain (LC) comprising the amino acid sequence pair specifically set forth in SEQ ID NOs: 18 & 20; 38 & 40; 54 & 56; 74 & 76; 94 & 96; 112 & 114; 132 & 134; 151 & 153; 169 & 171; 185 & 187; 203 & 205; 223 & 225; 241 & 243; 257 & 259; 275 & 277; 293 & 295; 311 & 313; 327 & 329; 345 & 347; 365 & 367; 383 & 385; 397 & 399; 413 & 415; 425 & 415; 435 & 415; 443 & 415; 453 & 415; 463 & 415; 473 & 415; 482 & 415; 491 & 415; 501 & 415; 511 & 415; 517 & 415; 527 & 415; 545 & 547; 565 & 567; 585 & 587; 605 & 607; and 617 & 607 (or a variant of any of said sequences), respectively; or that comprise a heavy chain or VH that comprises the CDRs thereof (HCDR1 (or a variant thereof), HCDR2 (or a variant thereof) and HCDR3 (or a variant thereof)) and / or a light chain or VL that comprises the CDRs thereof (LCDR1 (or a variant thereof), LCDR2 (or a variant thereof) and LCDR3 (or a variant thereof)). In an embodiment, the Vh is linked to an IgG constant heavy chain domain, for example, human IgG constant heavy chain domain (e.g., lgG1 or lgG4 (e.g., comprising the S228P and / or S108P mutation)) and / or the VL is linked to a light chain constant domain, for example a human light chain constant domain (e.g., lambda or kappa constant light chain domain). Polynucleotides encoding one or more of any such immunoglobulin chains (e.g., VH, Vl, HC and / or LC) forms part of the present disclosure.

[00197] Antibodies and antigen-binding fragments described herein (e.g., REGN14148;  REGN14149; REGN14150;  REGN14151; REGN14152; REGN14153; REGN14154;  REGN14155; REGN14156;  REGN14157; REGN14158; REGN14159; REGN14160;  REGN14161; REGN14162;  REGN14163; REGN14164; REGN14165; REGN14175;  REGN14176; REGN14177;  REGN14178; REGN14179; REGN14180; REGN14181; REGN14182; REGN14183;  REGN14184; REGN14185; REGN14186; REGN14187;  REGN14188; REGN14189;  REGN14190; REGN14191; REGN19513; REGN19514; REGN19515; REGN19516; or REGN19517) comprise immunoglobulin chains including the amino acid sequences specifically set forth herein (and variants thereof) as well as cellular and in vitro post-translational modifications to the antibody or fragment. For example, the present disclosure includes antibodies and antigen-binding fragments thereof that specifically bind to p75NTR comprising heavy and / or light chain amino acid sequences set forth herein as well as antibodies and fragments wherein one or more asparagine, serine and / or threonine residues is glycosylated, one or more asparagine residues is deamidated, one or more residues (e.g., Met, Trp and / or His) is oxidized, the N-terminal glutamine is pyroglutamate (pyroE) and / or the C-terminal lysine or other amino acid is missing.

[00198] The amino acid sequences of domains and chains in p75NTR binding proteins or p75NTR binding protein-drug conjugates of the present disclosure are summarized below in Table 1-1. For example, anti-p75NTR antibodies and antigen-binding fragments thereof (e.g., scFvs and Fabs) comprising the HCVR and LCVR of the molecules in Table 1-1; or comprising the CDRs thereof, or comprising the HC and LC of the molecules in Table 1-1, optionally conjugated to a molecular cargo, form part of the present disclosure. Table 1-1. SEQ ID NOs of Amino Acid Sequences of Domains in Antibodies or Antigen-binding Fragments (e.g., Fabs or scFv Molecules) or Protein-Drug Conjugates of the Present Disclosure. # anti-p75NTR Molecule HCVR HCDR1 HCDR2 HCDR3 LCVR LCDR1 LCDR2 LCDR3 HC LC 1 REGN14148 2 4 6 8 10 12 14 16 18 20 2 REGN14149 22 24 26 28 30 32 34 36 38 40 3 REGN14150 42 44 46 48 50 12 14 52 54 56 4 REGN14151 58 60 62 64 66 68 70 72 74 76 5 REGN14152 78 80 82 84 86 88 90 92 94 96 6 REGN14153 98 100 102 104 106 108 34 110 112 114 7 REGN14154 116 118 120 122 124 126 128 130 132 134 8 REGN14155 136 138 140 142 144 146 90 149 151 153 9 REGN14156 155 100 158 160 162 164 90 167 169 171 10 REGN14157 173 100 175 177 179 181 70 183 185 187 11 REGN14158 189 191 193 195 197 199 14 201 203 205 12 REGN14159 207 209 211 213 215 217 219 221 223 225 13 REGN14160 227 229 231 233 235 237 14 239 241 243 14 REGN14161 245 100 247 249 251 253 70 255 257 259 15 REGN14162 261 263 265 267 269 271 90 273 275 277 16 REGN14163 279 281 283 285 287 289 14 291 293 295 17 REGN14164 297 299 193 302 304 237 307 309 311 313 18 REGN14165 315 317 319 321 323 12 14 325 327 329 19 REGN14175 331 333 335 337 339 237 341 343 345 347 20 REGN14176 349 351 353 355 357 359 361 363 365 367 21 REGN14177 369 371 373 375 377 379 90 381 383 385 22 REGN14178 387 138 319 389 391 393 361 395 397 399 23 REGN14179 401 403 405 407 409 237 14 411 413 415 24 REGN14180 417 419 421 423 409 237 14 411 425 415 25 REGN14181 427 429 431 433 409 237 14 411 435 415 26 REGN14182 437 191 335 441 409 237 14 411 443 415 27 REGN14183 445 447 449 451 409 237 14 411 453 415 28 REGN14184 455 457 459 461 409 237 14 411 463 415 29 REGN14185 465 467 469 471 409 237 14 411 473 415 30 REGN14186 475 477 158 480 409 237 14 411 482 415 31 REGN14187 484 486 283 489 409 237 14 411 491 415 32 REGN14188 493 495 497 499 409 237 14 411 501 415 33 REGN14189 503 505 507 509 409 237 14 411 511 415 34 REGN14190 513 138 319 515 409 237 14 411 517 415 35 REGN14191 519 521 523 525 409 237 14 411 527 415 36 REGN19513 529 531 533 535 537 539 541 543 545 547 37 REGN19514 549 551 553 555 557 559 561 563 565 567 38 REGN19515 569 571 573 575 577 579 581 583 585 587 39 REGN19516 589 591 593 595 597 599 601 603 605 607 40 REGN19517 609 611 613 615 597 599 601 603 617 607

[00199] Amino acid and nucleotide sequences of domains or chains in anti-p75NTR antibodies or antigen-binding fragments (e.g., Fabs or scFv molecules) or protein-drug conjugates described herein are set forth below. The nucleotide sequences encoding the amino acid sequences of domains or chains in p75NTR binding proteins or protein-drug conjugates of the present disclosure are also summarized within Table 1-2. The present disclosure includes any antibody or antigen-binding fragment thereof that includes an HCVR and LCVR having a sequence as set forth below or an HCVR and LCVR having the HCDRs and LCDRs thereof, respectively. REG N14148 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCGGCCTCTGGATTCACCTTTAATAACTATTGGATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCCAGATGGAAGTGA GAAATCATATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AAATCACTGTTTCTGCAAATGACCAGCCTGAGAGCCGAGGACACGGCTGTTTATTACT GTGCGACGAACTGGGGGTTTGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQIDNO: 1) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYWMSWIRQAPGKGLEWVANIKPDGSEKS YVDSVKGRFTISRDNAKKSLFLQMTSLRAEDTAVYYCATNWGFDWGQGTLVTVSS (SEQ ID NO: 2) CDR1 DNA Sequence GGA TTC ACC TTT AAT AAC TAT TGG (SEQ ID NO: 3) CDR1 Amino Acid Sequence GFTFNNYW (SEQ ID NO: 4) CDR2 DNA Sequence ATA AAG CCA GAT GGA AGT GAG AAA (SEQ ID NO: 5) CDR2 Amino Acid Sequence I K P D G S E K (SEQ ID NO: 6) CDR3 DNA Sequence GCG ACG AAC TGG GGG TTT GAC (SEQ ID NO: 7) CDR3 Amino Acid Sequence A T N W G F D (SEQ ID NO: 8) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAGAGTCA CCGTCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGACTTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGTATAATAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTVTCRASQDIRNDLGWFQQKPGKAPKRLIYAASSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCLQYNSYPWTFGQGTKVEIK (SEQ ID NO: 10) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) CDR1 Amino Acid Sequence Q D I R N D (SEQ ID NO: 12) CDR2 DNA Sequence GOT GCA TOC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG TAT AAT AGT TAC CCG TGG ACG (SEQ ID NO: 15) CDR3 Amino Acid Sequence LQYNSYPWT (SEQ ID NO: 16) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCGGCCTCTGGATTCACCTTTAATAACTATTGGATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCCAGATGGAAGTGA GAAATCATATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AAATCACTGTTTCTGCAAATGACCAGCCTGAGAGCCGAGGACACGGCTGTTTATTACT GTGCGACGAACTGGGGGTTTGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG CCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCG AGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTAC AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG GCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACA AGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCACCTGTGG CAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCG GACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCC AGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGG AGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGG ACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCT CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACA CCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGG TCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG AGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTA CAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTC CGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTG GGTAAATGA (SEQIDNO: 17) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYWMSWIRQAPGKGLEWVANIKPDGSEKS YVDSVKGRFTISRDNAKKSLFLQMTSLRAEDTAVYYCATNWGFDWGQGTLVTVSSASTKG PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKP KDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLT VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGK* (SEQIDNO: 18) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAGAGTCA CCGTCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGACTTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGTATAATAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQIDNO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTVTCRASQDIRNDLGWFQQKPGKAPKRLIYAASSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCLQYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REG N14149 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCACCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGCTACTGGTAGTGGC ACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGAGAATTCCAAGA ACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGTGAAAGGTCCGTATAGTAACAGCCGGAACGTGGGCTTCCAGCACTGGGGCCAGGG CACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 21) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTTYAMSWVRQAPGKGLEWVSAISATGSGTY YADSVKGRFTISRENSKNTLYLQMKSLRAEDTAVYYCVKGPYSNSRNVGFQHWGQGTLV TVSS (SEQ ID NO: 22) CDR1 DNA Sequence GGA TTC ACC TTT ACC ACC TAT GCC (SEQ ID NO: 23) CDR1 Amino Acid Sequence GFTFTTYA (SEQ ID NO: 24) CDR2 DNA Sequence ATT AGT GCT ACT GGT AGT GGC ACA (SEQ ID NO: 25) CDR2 Amino Acid Sequence I S A T G S G T (SEQ ID NO: 26) CDR3 DNA Sequence GTG AAA GGT CCG TAT AGT AAC AGC CGG AAC GTG GGC TTC CAG CAC (SEQ ID NO: 27) CDR3 Amino Acid Sequence VKGPYSNSRNVGFQH (SEQ ID NO: 28) LCVR DNA Sequence GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTACATAGTAATGGATACAACTATTTGGAT TGGTACCTGCAGAAGCCAGGGCAGTCTCCACAACTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTTCTGCATGCAACATCT ACAAACTCCCATGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 29) LCVR Amino Acid Sequence DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCMQHLQTPMYTFGQGTKLEIK (SEQ ID NO: 30) CDR1 DNA Sequence CAG AGO CTO CTA CAT AGT AAT GGA TAC AAC TAT (SEQ ID NO: 31) CDR1 Amino Acid Sequence QSLLHSNGYNY (SEQ ID NO: 32) CDR2 DNA Sequence TTG GGT TCT (SEQ ID NO: 33) CDR2 Amino Acid Sequence L G S (SEQ ID NO: 34) CDR3 DNA Sequence ATG CAA CAT CTA CAA ACT CCC ATG TAC ACT (SEQ ID NO: 35) CDR3 Amino Acid Sequence MQHLQTPMYT (SEQ ID NO: 36) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTACCACCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGCTACTGGTAGTGGC ACATACTATGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGAGAATTCCAAGA ACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGTGAAAGGTCCGTATAGTAACAGCCGGAACGTGGGCTTCCAGCACTGGGGCCAGGG CACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGC GCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGG ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCG TGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT GACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAA GCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC ACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTG AGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCAT AATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGC GTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC CCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACT CCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGG AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACA GAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 37) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFTTYAMSWVRQAPGKGLEWVSAISATGSGTY YADSVKGRFTISRENSKNTLYLQMKSLRAEDTAVYYCVKGPYSNSRNVGFQHWGQGTLV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 38) LC DNA Sequence GATATTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTACATAGTAATGGATACAACTATTTGGAT TGGTACCTGCAGAAGCCAGGGCAGTCTCCACAACTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTTCTGCATGCAACATCT ACAAACTCCCATGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 39) LC Amino Acid Sequence DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYFCMQHLQTPMYTFGQGTKLEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 40) REGN14150 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAA GTCTCCTGTAAGGCTTCTGGTTACACCTTTAGTAGCCATGGTATCACCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTATAATGGTGACA CAAACTATGCACAGAAAGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAG TACAGCCTACATGGAACTGAGGAGCCTGAGATCTGACGACACGGCCGTGTTTTACTGT GCGCGATATAGGGGAATAGTAGGTCGTAATTACAACTACTATGGTATGGACGTCTGGG GCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 41) HCVR Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFSSHGITWVRQAPGQGLEWMGWISAYNGDT NYAQKVQGRVTMTTDTSTSTAYMELRSLRSDDTAVFYCARYRGIVGRNYNYYGMDVWG QGTTVTVSS (SEQ ID NO: 42) CDR1 DNA Sequence GGT TAC ACC TTT AGT AGC CAT GGT (SEQ ID NO: 43) CDR1 Amino Acid Sequence GYTFSSHG (SEQ ID NO: 44) CDR2 DNA Sequence ATC AGC GCT TAT AAT GGT GAC ACA (SEQ ID NO: 45) CDR2 Amino Acid Sequence I S A Y N G D T (SEQ ID NO: 46) CDR3 DNA Sequence GCG CGA TAT AGG GGA ATA GTA GGT CGT AAT TAC AAC TAC TAT GGT ATG GAC GTC (SEQ ID NO: 47) CDR3 Amino Acid Sequence ARYRGIVGRNYNYYGMDV (SEQ ID NO: 48) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAGAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATGTATGCTGCATCCAGTTTGCAAAGTGGGGT CCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCACC CTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAATAGTTACCCCCTCAC TTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 49) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGERVTITCRASQDIRNDLGWYQQKPGKAPKRLMYAASSLQSGVPS RFSGSGSGTEFTLTISTLQPEDFATYYCLQHNSYPLTFGGGTKVEIK (SEQ ID NO: 50) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) CDR1 Amino Acid Sequence Q D I R N D (SEQ ID NO: 12) CDR2 DNA Sequence GCT GCA TCC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG CAT AAT AGT TAC CCC CTC ACT (SEQ ID NO: 51) CDR3 Amino Acid Sequence LQHNSYPLT (SEQ ID NO: 52) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAA GTCTCCTGTAAGGCTTCTGGTTACACCTTTAGTAGCCATGGTATCACCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTATAATGGTGACA CAAACTATGCACAGAAAGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAG TACAGCCTACATGGAACTGAGGAGCCTGAGATCTGACGACACGGCCGTGTTTTACTGT GCGCGATATAGGGGAATAGTAGGTCGTAATTACAACTACTATGGTATGGACGTCTGGG GCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCC CCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTG GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACC AGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC ATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCC AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 53) HC Amino Acid Sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFSSHGITWVRQAPGQGLEWMGWISAYNGDT NYAQKVQGRVTMTTDTSTSTAYMELRSLRSDDTAVFYCARYRGIVGRNYNYYGMDVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 54) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAGAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTGATGTATGCTGCATCCAGTTTGCAAAGTGGGGT CCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCACC CTGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAATAGTTACCCCCTCAC TTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG (SEQ ID NO: 55) LC Amino Acid Sequence DIQMTQSPSSLSASVGERVTITCRASQDIRNDLGWYQQKPGKAPKRLMYAASSLQSGVPS RFSGSGSGTEFTLTISTLQPEDFATYYCLQHNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 56) REGN14151 HCVR DNA Sequence CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCA CTCACCTGTGCCTTCTCCGGGGACAGTGTCTCTAGGAACAGTGCTGCTTGGAACTGGA TCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCA AGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACA GCCAAGAACCAGTTCTCCCTGCAGCTGAAATCTGTGACTCCCGAGGACACGGCTGTGT ATTACTGTGCAAGAGAGGGGCCCTATTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCA (SEQ ID NO: 57) HCVR Amino Acid Sequence QVQLQQSGPGLVKPSQTLSLTCAFSGDSVSRNSAAWNWIRQSPSRGLEWLGRTYYRSK WYNDYAVSVKSRITINPDTAKNQFSLQLKSVTPEDTAVYYCAREGPYFDYWGQGTLVTVS S (SEQ ID NO: 58) CDR1 DNA Sequence GGG GAC AGT GTC TOT AGG AAC AGT GOT GOT (SEQ ID NO: 59) CDR1 Amino Acid Sequence GDSVSRNSAA (SEQ ID NO: 60) CDR2 DNA Sequence ACA TAC TAC AGG TGC AAG TGG TAT AAT (SEQ ID NO: 61) CDR2 Amino Acid Sequence TYYRSKWYN (SEQ ID NO: 62) CDR3 DNA Sequence GCA AGA GAG GGG CCC TAT TTT GAC TAC (SEQ ID NO: 63) CDR3 Amino Acid Sequence AREGPYFDY (SEQ ID NO: 64) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTACACAGCTCCAACAATATGAACTACTT AGCTTGGTACCAGCAGAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCT ACCCGGAAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTTCAGGCTGCTGATGTGGCAGTTTATTACTGTCTGCAATA TTATAATACTCCTCGAACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 65) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLHSSNNMNYLAWYQQKPGQPPKLLIYWASTR KSGVPDRFSGSGSGTDFTLTISSLQAADVAVYYCLQYYNTPRTFGQGTKVEIK (SEQ ID NO: 66) CDR1 DNA Sequence CAG AGT GTT TTA CAC AGC TCC AAC AAT ATG AAC TAC (SEQ ID NO: 67) CDR1 Amino Acid Sequence QSVLHSSNNMNY (SEQ ID NO: 68) CDR2 DNA Sequence TGG GCA TOT (SEQ ID NO: 69) CDR2 Amino Acid Sequence WAS (SEQ ID NO: 70) CDR3 DNA Sequence CTG CAA TAT TAT AAT ACT CCT CGA ACG (SEQ ID NO: 71) CDR3 Amino Acid Sequence LQYYNTPRT (SEQ ID NO: 72) HC DNA Sequence CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCA CTCACCTGTGCCTTCTCCGGGGACAGTGTCTCTAGGAACAGTGCTGCTTGGAACTGGA TCAGGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCA AGTGGTATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACA GCCAAGAACCAGTTCTCCCTGCAGCTGAAATCTGTGACTCCCGAGGACACGGCTGTGT ATTACTGTGCAAGAGAGGGGCCCTATTTTGACTACTGGGGCCAGGGAACCCTGGTCA CCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCA GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCG AACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAG CACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCT CATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGA CCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGT CCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCC ACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCT GACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC CTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGT CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTC TCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 73) HC Amino Acid Sequence QVQLQQSGPGLVKPSQTLSLTCAFSGDSVSRNSAAWNWIRQSPSRGLEWLGRTYYRSK WYNDYAVSVKSRITINPDTAKNQFSLQLKSVTPEDTAVYYCAREGPYFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY RWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 74) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTACACAGCTCCAACAATATGAACTACTT AGCTTGGTACCAGCAGAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCT ACCCGGAAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTTCAGGCTGCTGATGTGGCAGTTTATTACTGTCTGCAATA TTATAATACTCCTCGAACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 75) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLHSSNNMNYLAWYQQKPGQPPKLLIYWASTR KSGVPDRFSGSGSGTDFTLTISSLQAADVAVYYCLQYYNTPRTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 76) REG N14152 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGAGGGAGGCTGGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGAATCACCTTTAGCATCTATGCCATGGCCTGGGTCCGC CAGGCTCCAGGGAAGGGACTTGAGTGGGTCTCAACTATTAGTGGTAGTGGTGATTCCA CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGTGGACACGGCCATATATTACTGT GCGAAAAGAGGATTTGCAGCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTC TCCTCA (SEQ ID NO: 77) HCVR Amino Acid Sequence EVQLVESEGGWVQPGGSLRLSCAASGITFSIYAMAWVRQAPGKGLEWVSTISGSGDSTY YADSVKGRFTISRDNSKNTLFLQMNSLRAVDTAIYYCAKRGFAAFDYWGQGTLVTVSS (SEQ ID NO: 78) CDR1 DNA Sequence GGA ATC ACC TTT AGC ATC TAT GCC (SEQ ID NO: 79) CDR1 Amino Acid Sequence G I T F S I Y A (SEQ ID NO: 80) CDR2 DNA Sequence ATT AGT GGT AGT GGT GAT TCC ACA (SEQ ID NO: 81) CDR2 Amino Acid Sequence I S G S G D S T (SEQ ID NO: 82) CDR3 DNA Sequence GCG AAA AGA GGA TTT GCA GCT TTT GAC TAC (SEQ ID NO: 83) CDR3 Amino Acid Sequence AKRGFAAFDY (SEQ ID NO: 84) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGTAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGTCTCCCAGGCTCCTCATCTATGGTGCATCAAACAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGTC TGCTCAGTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 85) LCVR Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQSPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRLLSFGGGTKVEIK (SEQ ID NO: 86) CDR1 DNA Sequence CAG AGT GTT AGC AGC ACC TAC (SEQ ID NO: 87) CDR1 Amino Acid Sequence Q S V S S T Y (SEQ ID NO: 88) CDR2 DNA Sequence GGT GCA TCA (SEQ ID NO: 89) CDR2 Amino Acid Sequence GAS (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGC TCA CGT CTG CTC AGT (SEQ ID NO: 91) CDR3 Amino Acid Sequence QQYGSSRLLS (SEQ ID NO: 92) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGAGGGAGGCTGGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGAATCACCTTTAGCATCTATGCCATGGCCTGGGTCCGC CAGGCTCCAGGGAAGGGACTTGAGTGGGTCTCAACTATTAGTGGTAGTGGTGATTCCA CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAA CACGCTGTTTCTGCAAATGAACAGCCTGAGAGCCGTGGACACGGCCATATATTACTGT GCGAAAAGAGGATTTGCAGCTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTC TCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGC ACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCG GTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC AGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAG GTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCA CCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGA TCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCC GAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAG CCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG CACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTC CCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAG GTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC TGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTC TCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCC TGTCTCTGGGTAAATGA (SEQ ID NO: 93) HC Amino Acid Sequence EVQLVESEGGWVQPGGSLRLSCAASGITFSIYAMAWVRQAPGKGLEWVSTISGSGDSTY YADSVKGRFTISRDNSKNTLFLQMNSLRAVDTAIYYCAKRGFAAFDYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFP PKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 94) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGTAGGGCCAGTCAGAGTGTTAGCAGCACCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGTCTCCCAGGCTCCTCATCTATGGTGCATCAAACAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGTC TGCTCAGTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCAT CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTG TGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCA CCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAG TCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA ACAGGGGAGAGTGTTAG (SEQ ID NO: 95) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLAWYQQKPGQSPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRLLSFGGGTKVEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 96) REGN14153 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATGCCATGAACTGGGTCCGC CAGGCTCCAGGGGAGGGCCTGGAGTGGGTCTCAACTTTGACTGGTAGTGGTGGTAGT ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAAGGTGGAGTGGGATCTACTAAGGTTGTCTACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 97) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMNVWRQAPGEGLEWVSTLTGSGGST YYADSVKGRFTISRDNSKNTLFLHMSSLRAEDTAVYYCAKGGVGSTKVVYYGLDVWGQG TTVTVSS (SEQ ID NO: 98) CDR1 DNA Sequence GGA TTC ACC TTT AGT AGT TAT GCC (SEQ ID NO: 99) CDR1 Amino Acid Sequence GFTFSSYA (SEQ ID NO: 100) CDR2 DNA Sequence TTG ACT GGT AGT GGT GGT AGT ACA (SEQ ID NO: 101) CDR2 Amino Acid Sequence LTGSGGST (SEQ ID NO: 102) CDR3 DNA Sequence GCG AAA GGT GGA GTG GGA TCT ACT AAG GTT GTC TAC TAC GGT TTG GAC GTC (SEQ ID NO: 103) CDR3 Amino Acid Sequence AKGGVGSTKVVYYGLDV (SEQ ID NO: 104) LCVR DNA Sequence GATATTGTGATGACTCAGTCTCCACTTTCCCTGCCCGTCATCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATCGTAATGGATACAACTTTTTGGAT TGGTACCTGCGGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCT ACAAACTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 105) LCVR Amino Acid Sequence DIVMTQSPLSLPVIPGEPASISCRSSQSLLHRNGYNFLDWYLRKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 106) CDR1 DNA Sequence CAG AGO CTO CTG CAT CGT AAT GGA TAC AAC TTT (SEQ ID NO: 107) CDR1 Amino Acid Sequence QSLLHRNGYNF (SEQ ID NO: 108) CDR2 DNA Sequence TTG GGT TOT (SEQ ID NO: 33) CDR2 Amino Acid Sequence L G S (SEQ ID NO: 34) CDR3 DNA Sequence ATG CAA GOT CTA CAA ACT CCG CTC ACT (SEQ ID NO: 109) CDR3 Amino Acid Sequence MQALQTPLT (SEQIDNO: 110) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATGCCATGAACTGGGTCCGC CAGGCTCCAGGGGAGGGCCTGGAGTGGGTCTCAACTTTGACTGGTAGTGGTGGTAGT ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGAAAGGTGGAGTGGGATCTACTAAGGTTGTCTACTACGGTTTGGACGTCTGGGG CCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCC CCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGG TCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC ATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCC AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQIDNO: 111) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGEGLEWVSTLTGSGGST YYADSVKGRFTISRDNSKNTLFLHMSSLRAEDTAVYYCAKGGVGSTKWYYGLDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQIDNO: 112) LC DNA Sequence GATATTGTGATGACTCAGTCTCCACTTTCCCTGCCCGTCATCCCTGGAGAGCCGGCCT CCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATCGTAATGGATACAACTTTTTGGAT TGGTACCTGCGGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATC GGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACAC TGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCT ACAAACTCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGT GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA ACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGTTAG (SEQIDNO: 113) LC Amino Acid Sequence DIVMTQSPLSLPVIPGEPASISCRSSQSLLHRNGYNFLDWYLRKPGQSPQLLIYLGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIKRTVAAPSVFI FPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQIDNO: 114) REG N14154 HCVR DNA Sequence CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACTTGCACTGTCTCGGGTGGCTCCAGCAGCAGAAGTAGTTACTACTGGGGCTG GATCCGCCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGAGTATCTATTATAGTGG GAACACCTACTACAACCCGTCCCTCCAGAGTCGAGTCACCATATCCGTAGACACGTCC AAGAACCAGTTCTCCCTGAAACTGAACTCTGTGACCGCCGCAGACACGGCTGTATTTT ATTGTGCGAGACACAAACCTACTACGTGGGCTTTTGATATCTGGGGCCAAGGGACAAT GGTCACCGTCTCTTCA (SEQIDNO: 115) HCVR Amino Acid Sequence QLQLQESGPGLVKPSETLSLTCTVSGGSSSRSSYYWGWIRQPPGKGLEWIGSIYYSGNTY YNPSLQSRVTISVDTSKNQFSLKLNSVTAADTAVFYCARHKPTTWAFDIWGQGTMVTVSS (SEQ ID NO: 116) CDR1 DNA Sequence GGT GGC TOO AGO AGO AGA AGT AGT TAC TAC (SEQ ID NO: 117) CDR1 Amino Acid Sequence GGSSSRSSYY (SEQ ID NO: 118) CDR2 DNA Sequence ATC TAT TAT AGT GGG AAC ACC (SEQ ID NO: 119) CDR2 Amino Acid Sequence I Y Y S G N T (SEQIDNO: 120) CDR3 DNA Sequence GCG AGA CAC AAA CCT ACT ACG TGG GCT TTT GAT ATC (SEQ ID NO: 121) CDR3 Amino Acid Sequence ARHKPTTWAFDI (SEQ ID NO: 122) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCCAGTCAGAGTATCAGTAGTTGGTTGGCCTGGTATCAGCAGAA ACCAGGGAAAGTCCCAAAGTTGCTGATCTATAAGGCGTCTAATTTAGAAAGTGGGGTC CCCTCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCGACC TGCAGCCTGATGATTTTGCAAGTTATTACTGCCAACAGTATAGTACTTATTCTCGGACG TTCGGCCGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 123) LCVR Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKVPKLLIYKASNLESGVPSR FSGSGSGTEFTLTISDLQPDDFASYYCQQYSTYSRTFGRGTKVEIK (SEQ ID NO: 124) CDR1 DNA Sequence CAG AGT ATO AGT AGT TGG (SEQ ID NO: 125) CDR1 Amino Acid Sequence Q S I S S W (SEQ ID NO: 126) CDR2 DNA Sequence AAG GOG TOT (SEQ ID NO: 127) CDR2 Amino Acid Sequence KAS (SEQ ID NO: 128) CDR3 DNA Sequence CAA CAG TAT AGT ACT TAT TCT CGG ACG (SEQIDNO: 129) CDR3 Amino Acid Sequence QQYSTYSRT (SEQIDNO: 130) HC DNA Sequence CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACTTGCACTGTCTCGGGTGGCTCCAGCAGCAGAAGTAGTTACTACTGGGGCTG GATCCGCCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGGAGTATCTATTATAGTGG GAACACCTACTACAACCCGTCCCTCCAGAGTCGAGTCACCATATCCGTAGACACGTCC AAGAACCAGTTCTCCCTGAAACTGAACTCTGTGACCGCCGCAGACACGGCTGTATTTT ATTGTGCGAGACACAAACCTACTACGTGGGCTTTTGATATCTGGGGCCAAGGGACAAT GGTCACCGTCTCTTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTG CTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAG CAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTG CCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAG GAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAAC AAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA GAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGG AATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGT CCCTCTCCCTGTCTCTGGGTAAATGA (SEQIDNO: 131) HC Amino Acid Sequence QLQLQESGPGLVKPSETLSLTCTVSGGSSSRSSYYWGWIRQPPGKGLEWIGSIYYSGNTY YNPSLQSRVTISVDTSKNQFSLKLNSVTAADTAVFYCARHKPTTWAFDIWGQGTMVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 132) LC DNA Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCCAGTCAGAGTATCAGTAGTTGGTTGGCCTGGTATCAGCAGAA ACCAGGGAAAGTCCCAAAGTTGCTGATCTATAAGGCGTCTAATTTAGAAAGTGGGGTC CCCTCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCGACC TGCAGCCTGATGATTTTGCAAGTTATTACTGCCAACAGTATAGTACTTATTCTCGGACG TTCGGCCGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQIDNO: 133) LC Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKVPKLLIYKASNLESGVPSR FSGSGSGTEFTLTISDLQPDDFASYYCQQYSTYSRTFGRGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQIDNO: 134) REG N14155 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGACTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGTCTACAGTGGTAAAA AAAACTACGCACGGAAGGTCCAGGACAGAGTCACCATGACCACAGACACATCCACGA GCACAGCCTACATGGAGGTGAGGAGCCTGCGATCTGACGACACGGCCATATATTATTG TACAAGAAGGGGAGTGTCTTCGATGGTCGGTGCTTTTGAAATCTGGGGCCAAGGGAC AATGGTCACCGTCTCTTCA (SEQ ID NO: 135) HCVR Amino Acid Sequence QVQLVQSGGEVKKPGDSVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISVYSGKK NYARKVQDRVTMTTDTSTSTAYMEVRSLRSDDTAIYYCTRRGVSSMVGAFEIWGQGTMV TVSS (SEQIDNO: 136) CDR1 DNA Sequence GGT TAC ACC TTT ACC AGC TAT GGT (SEQIDNO: 137) CDR1 Amino Acid Sequence GYTFTSYG (SEQ ID NO: 138) CDR2 DNA Sequence ATC AGC GTC TAC AGT GGT AAA AAA (SEQ ID NO: 139) CDR2 Amino Acid Sequence I S V Y S G K K (SEQIDNO: 140) CDR3 DNA Sequence ACA AGA AGG GGA GTG TCT TCG ATG GTC GGT GCT TTT GAA ATC (SEQ ID NO: 141) CDR3 Amino Acid Sequence TRRGVSSMVGAFEI (SEQ ID NO: 142) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCATTCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAAGGCCAGTCAGAGTGTTAGCAACAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATCTAGTAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTGTCACCATCAG CAGACTGGAGCCTGAAGATTTTGCAGTCTATTACTGTCAGCAGTATGGTAGCTCACCG CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQIDNO: 143) LCVR Amino Acid Sequence EIVLTQSPGILSLSPGERATLSCKASQSVSNSYLAWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTVTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK (SEQ ID NO: 144) CDR1 DNA Sequence CAG AGT GTT AGO AAC AGO TAC (SEQIDNO: 145) CDR1 Amino Acid Sequence Q S V S N S Y (SEQ ID NO: 146) CDR2 DNA Sequence GGA GCA TCT (SEQ ID NO: 147) CDR2 Amino Acid Sequence GAS (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGO TCA COG CTC ACT (SEQ ID NO: 148) CDR3 Amino Acid Sequence QQYGSSPLT (SEQ ID NO: 149) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGACTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGTCTACAGTGGTAAAA AAAACTACGCACGGAAGGTCCAGGACAGAGTCACCATGACCACAGACACATCCACGA GCACAGCCTACATGGAGGTGAGGAGCCTGCGATCTGACGACACGGCCATATATTATTG TACAAGAAGGGGAGTGTCTTCGATGGTCGGTGCTTTTGAAATCTGGGGCCAAGGGAC AATGGTCACCGTCTCTTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCC CTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTA CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGC ACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCC CAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACC GTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAG GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCC AACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC CGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAG GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAG GGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGA AGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 150) HC Amino Acid Sequence QVQLVQSGGEVKKPGDSVKVSCKASGYTFTSYGISVWRQAPGQGLEWMGWISVYSGKK NYARKVQDRVTMTTDTSTSTAYMEVRSLRSDDTAIYYCTRRGVSSMVGAFEIWGQGTMV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 151) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCATTCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAAGGCCAGTCAGAGTGTTAGCAACAGCTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGAGCATCTAGTAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTGTCACCATCAG CAGACTGGAGCCTGAAGATTTTGCAGTCTATTACTGTCAGCAGTATGGTAGCTCACCG CTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCT GTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTG CCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCT ACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACA GGGGAGAGTGTTAG (SEQIDNO: 152) LC Amino Acid Sequence EIVLTQSPGILSLSPGERATLSCKASQSVSNSYLAWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTVTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 153) REG N14156 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGAGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAGTGGTGGTAAC ACATACTACGCAGTCTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACACTTCCAAGA ACACGCTGTATCTGCAAATGAACGGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGACCCTCACCAGTGGCTGGTACCTTTTTGAGTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA (SEQ ID NO: 154) HCVR Amino Acid Sequence E VQLVESGGG LVQ PG ES LRLSCAASG FT FSSYAMTWVRQAPG KG LE WVSTISGSGG NTY YAVSVKGRFTISRDTSKNTLYLQMNGLRAEDTAVYYCATLTSGWYLFEYWGQGTLVTVSS (SEQ ID NO: 155) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC (SEQIDNO: 156) CDR1 Amino Acid Sequence GFTFSSYA (SEQ ID NO: 100) CDR2 DNA Sequence ATT AGT GGT AGT GGT GGT AAC ACA (SEQIDNO: 157) CDR2 Amino Acid Sequence I S G S G G N T (SEQIDNO: 158) CDR3 DNA Sequence GCG ACC CTC ACC AGT GGC TGG TAC CTT TTT GAG TAC (SEQ ID NO: 159) CDR3 Amino Acid Sequence ATLTSGWYLFEY (SEQ ID NO: 160) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGGCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTTCTTTGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGAAGCTCACCTC CGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 161) LCVR Amino Acid Sequence EIVLTQSPGTLSLAPGERATLSCRASQSVSSSFFAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIK (SEQIDNO: 162) CDR1 DNA Sequence CAG AGT GTT AGC AGC AGC TTC (SEQIDNO: 163) CDR1 Amino Acid Sequence Q S V S S S F (SEQ ID NO: 164) CDR2 DNA Sequence GGT GCA TCC (SEQ ID NO: 165) CDR2 Amino Acid Sequence GAS (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGA AGO TCA OCT COG TGG ACG (SEQ ID NO: 166) CDR3 Amino Acid Sequence QQYGSSPPWT (SEQ ID NO: 167) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGAGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAGTGGTGGTAAC ACATACTACGCAGTCTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACACTTCCAAGA ACACGCTGTATCTGCAAATGAACGGCCTGAGAGCCGAGGACACGGCCGTATATTACTG TGCGACCCTCACCAGTGGCTGGTACCTTTTTGAGTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTC CAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC CGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA CACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCC AGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAG CCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAAT GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCC TCTCCCTGTCTCTGGGTAAATGA (SEQIDNO: 168) HC Amino Acid Sequence E VQLVESGGG LVQ PG ES LRLSCAASG FT FSSYAMTWVRQAPG KG LE WVSTISGSGG NTY YAVSVKGRFTISRDTSKNTLYLQMNGLRAEDTAVYYCATLTSGWYLFEYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQIDNO: 169) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGGCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTTCTTTGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGAAGCTCACCTC CGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCAT CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTG TGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCA CCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAG TCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA ACAGGGGAGAGTGTTAG (SEQIDNO: 170) LC Amino Acid Sequence EIVLTQSPGTLSLAPGERATLSCRASQSVSSSFFAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQIDNO: 171) REGN14157 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGTCGAGGATACGGCCGTATATTATTG TGCGAAAGAGAAGAGCAGTGGCTGGTACGAATACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCA (SEQIDNO: 172) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCAKEKSSGWYEYWGQGTLVTVSS (SEQ ID NO: 173) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC (SEQIDNO: 156) CDR1 Amino Acid Sequence GFTFSSYA (SEQ ID NO: 100) CDR2 DNA Sequence ATT AGT GGT AGT GGT GAT AAC ACA (SEQ ID NO: 174) CDR2 Amino Acid Sequence I S G S G D N T (SEQ ID NO: 175) CDR3 DNA Sequence GCG AAA GAG AAG AGO AGT GGC TGG TAC GAA TAC (SEQ ID NO: 176) CDR3 Amino Acid Sequence AKEKSSGWYEY (SEQIDNO: 177) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATACAGTTCCAACAATAAGAATTACTT AGCTTGGTACCAGCAGAAACCAGGACAGACTCCTAAACTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAT ATTATTTTATTCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 178) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQTPKLLIYWASTRE SGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYFIPYTFGQGTKLEIK (SEQIDNO: 179) CDR1 DNA Sequence CAG AGT GTT TTA TAC AGT TCC AAC AAT AAG AAT TAC (SEQIDNO: 180) CDR1 Amino Acid Sequence QSVLYSSNNKNY (SEQ ID NO: 181) CDR2 DNA Sequence TGG GCA TOT (SEQ ID NO: 69) CDR2 Amino Acid Sequence WAS (SEQ ID NO: 70) CDR3 DNA Sequence CAG CAA TAT TAT TTT ATT CCG TAC ACT (SEQIDNO: 182) CDR3 Amino Acid Sequence QQYYFIPYT (SEQ ID NO: 183) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGATAAC ACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGTCGAGGATACGGCCGTATATTATTG TGCGAAAGAGAAGAGCAGTGGCTGGTACGAATACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAG GAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGA ACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACAC CAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGC ACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCA CAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTG ACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAAT GGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC TTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCT CCCTGTCTCTGGGTAAATGA (SEQ ID NO: 184) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGDNTY YADSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCAKEKSSGWYEYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 185) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATACAGTTCCAACAATAAGAATTACTT AGCTTGGTACCAGCAGAAACCAGGACAGACTCCTAAACTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGCAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAAT ATTATTTTATTCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA GAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC AAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 186) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQTPKLLIYWASTRE SGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYFIPYTFGQGTKLEIKRTVAAPSVFI FPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 187) REG N14158 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCAGTTATATCATATGATGGAAGTAAC AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAGGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAACTGAGGACACGGCTGTGTTTTATTG TGCGAAAGAGTCGAGTATAACAGCCCGTCCGAGAGACTACAACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 188) HCVR Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSHYGMHVWRQAPGKGLEWMAVISYDGSNK YYADSVKGRFTISRDNSRNTLYLQMNSLRTEDTAVFYCAKESSITARPRDYNYGMDVWGQ GTTVTVSS (SEQ ID NO: 189) CDR1 DNA Sequence GGA TTC ACC TTC AGT CAC TAT GGC (SEQ ID NO: 190) CDR1 Amino Acid Sequence GFTFSHYG (SEQ ID NO: 191) CDR2 DNA Sequence ATA TCA TAT GAT GGA AGT AAC AAA (SEQ ID NO: 192) CDR2 Amino Acid Sequence I S Y D G S N K (SEQ ID NO: 193) CDR3 DNA Sequence GCG AAA GAG TCG AGT ATA ACA GCC CGT CCG AGA GAC TAC AAC TAG GGT ATG GAC GTC (SEQ ID NO: 194) CDR3 Amino Acid Sequence AKESSITARPRDYNYGMDV (SEQ ID NO: 195) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCGGCTATTTAAATTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAACTCCTAATCTATGCTGCATCCACTTTGCAAACTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCATCATCAGCAGTC TGCAGCCTGACGATTTTGCAACTTACCACTGTCAACAGAGTTACACTTCCCCTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 196) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWFQQKPGKAPKLLIYAASTLQTGVPSR FSGSGSGTDFTLIISSLQPDDFATYHCQQSYTSPFTFGPGTKVDIK (SEQ ID NO: 197) CDR1 DNA Sequence CAG AGO ATT AGO GGC TAT (SEQ ID NO: 198) CDR1 Amino Acid Sequence Q S I S G Y (SEQ ID NO: 199) CDR2 DNA Sequence GOT GCA TOC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG AGT TAC ACT TCC CCT TTC ACT (SEQ ID NO: 200) CDR3 Amino Acid Sequence QQSYTSPFT (SEQ ID NO: 201) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTCACTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGATGGCAGTTATATCATATGATGGAAGTAAC AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAGGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAACTGAGGACACGGCTGTGTTTTATTG TGCGAAAGAGTCGAGTATAACAGCCCGTCCGAGAGACTACAACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTC TTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTG CCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT CCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTC CCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAG CCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAG ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAG AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC AACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 202) HC Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSHYGMHWVRQAPGKGLEWMAVISYDGSNK YYADSVKGRFTISRDNSRNTLYLQMNSLRTEDTAVFYCAKESSITARPRDYNYGMDVWGQ GTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK S RWQ EG N VFSCSVM H EALH N H YTQ KS LS LSLG K* (SEQ ID NO: 203) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCGGCTATTTAAATTGGTTTCAGCAGAA ACCAGGGAAAGCCCCTAAACTCCTAATCTATGCTGCATCCACTTTGCAAACTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCATCATCAGCAGTC TGCAGCCTGACGATTTTGCAACTTACCACTGTCAACAGAGTTACACTTCCCCTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 204) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWFQQKPGKAPKLLIYAASTLQTGVPSR FSGSGSGTDFTLIISSLQPDDFATYHCQQSYTSPFTFGPGTKVDIKRTVAAPSVFIFPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 205) REG N14159 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCACAGCGGGGGGGGTCCCTGA GACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGACTATGCCGTGAGCTGGGTCCG CCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGCCGTGGTGGTGATTA CACGTACTACGCAGACTCCGTGAAGGGCCGGTTCATCATCTCCAGAGACAATTCCAAG AATATGTTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTATT GTGCGAAAAACTGGGGATCACTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT CCTCA (SEQ ID NO: 206) HCVR Amino Acid Sequence EVQLVESGGGLAQRGGSLRLSCAASGFTFSDYAVSWVRQAPGKGLEWVSGISRGGDYTY YADSVKGRFIISRDNSKNMLYLQMNSLRAEDTAVYYCAKNWGSLDYWGQGTLVTVSS (SEQ ID NO: 207) CDR1 DNA Sequence GGA TTC ACC TTT AGC GAC TAT GCC (SEQ ID NO: 208) CDR1 Amino Acid Sequence GFTFSDYA (SEQ ID NO: 209) CDR2 DNA Sequence ATT AGC CGT GGT GGT GAT TAC ACG (SEQ ID NO: 210) CDR2 Amino Acid Sequence I S R G G D Y T (SEQ ID NO: 211) CDR3 DNA Sequence GCG AAA AAC TGG GGA TCA CTT GAC TAC (SEQ ID NO: 212) CDR3 Amino Acid Sequence AKNWGSLDY (SEQ ID NO: 213) LCVR DNA Sequence GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAA ACCTGGCCAGGCTCCCAGACTCCTCATCTATGATGCATCCAACAGGGTCACTGGCATC CCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTCGAA CTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 214) LCVR Amino Acid Sequence EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRVTGIPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKLEIK (SEQ ID NO: 215) CDR1 DNA Sequence CAG AGT GTT AGO AGO TAC (SEQ ID NO: 216) CDR1 Amino Acid Sequence Q S V S S Y (SEQ ID NO: 217) CDR2 DNA Sequence GAT GCA TCC (SEQ ID NO: 218) CDR2 Amino Acid Sequence DAS (SEQ ID NO: 219) CDR3 DNA Sequence CAG CAG CGT AGC AAC TGG CCT CGA ACT (SEQ ID NO: 220) CDR3 Amino Acid Sequence QQRSNWPRT (SEQ ID NO: 221) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCACAGCGGGGGGGGTCCCTGA GACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCGACTATGCCGTGAGCTGGGTCCG CCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGCCGTGGTGGTGATTA CACGTACTACGCAGACTCCGTGAAGGGCCGGTTCATCATCTCCAGAGACAATTCCAAG AATATGTTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTATT GTGCGAAAAACTGGGGATCACTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT CCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCA CCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGG TGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCA GCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGG TGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCAC CTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGAT CTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCG AGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGC CGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGC ACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGG TGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT GCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT TCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCT GTCTCTGGGTAAATGA (SEQ ID NO: 222) HC Amino Acid Sequence EVQLVESGGGLAQRGGSLRLSCAASGFTFSDYAVSWVRQAPGKGLEWVSGISRGGDYTY YADSVKGRFIISRDNSKNMLYLQMNSLRAEDTAVYYCAKNWGSLDYWGQGTLVTVSSAST KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFP PKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 223) LC DNA Sequence GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAA ACCTGGCCAGGCTCCCAGACTCCTCATCTATGATGCATCCAACAGGGTCACTGGCATC CCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGC CTAGAGCCTGAAGATTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTCGAA CTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG (SEQ ID NO: 224) LC Amino Acid Sequence EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRVTGIPAR FSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKLEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 225) REG N14160 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTTACTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAATGGGTGACAGTTATATCATATGATGGAACTAAGA AACACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA CACCTTGTATCTGCAAATGAACAGCCTGAGAGCTGACGACACGGCTGTGTATTACTGT GCGAAAACGCATAGTACGTCATCCAGGGCCGACTACTTCTACGGTATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 226) HCVR Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSYYVMHWVRQAPGKGLEWVTVISYDGTKKH YADSVKGRFTISRDNSKNTLYLQMNSLRADDTAVYYCAKTHSTSSRADYFYGMDVWGQG TTVTVSS (SEQ ID NO: 227) CDR1 DNA Sequence GGA TTC ACC TTC AGT TAC TAT GTC (SEQ ID NO: 228) CDR1 Amino Acid Sequence GFTFSYYV (SEQ ID NO: 229) CDR2 DNA Sequence ATA TCA TAT GAT GGA ACT AAG AAA (SEQ ID NO: 230) CDR2 Amino Acid Sequence I S Y D G T K K (SEQ ID NO: 231) CDR3 DNA Sequence GCG AAA ACG CAT AGT ACG TCA TCC AGG GCC GAC TAG TTC TAG GGT ATG GAC GTC (SEQ ID NO: 232) CDR3 Amino Acid Sequence AKTHSTSSRADYFYGMDV (SEQ ID NO: 233) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTCAGTTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCTCCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 234) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPQFLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLLTFGGGTKVEIK (SEQ ID NO: 235) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TCC (SEQIDNO: 13) CDR2 Amino Acid Sequence A A S (SEQIDNO: 14) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CTC CTC ACT (SEQ ID NO: 238) CDR3 Amino Acid Sequence QQSYSTLLT (SEQ ID NO: 239) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTTACTATGTCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAATGGGTGACAGTTATATCATATGATGGAACTAAGA AACACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAA CACCTTGTATCTGCAAATGAACAGCCTGAGAGCTGACGACACGGCTGTGTATTACTGT GCGAAAACGCATAGTACGTCATCCAGGGCCGACTACTTCTACGGTATGGACGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTC CCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCT GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAG CAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGT AGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC CCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCC CCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGT GTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAG TGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAG CAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA CCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 240) HC Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSYYVMHWVRQAPGKGLEWVTVISYDGTKKH YADSVKGRFTISRDNSKNTLYLQMNSLRADDTAVYYCAKTHSTSSRADYFYGMDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 241) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAA ACCAGGGAAAGCCCCTCAGTTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTC CCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCTCCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 242) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPQFLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLLTFGGGTKVEIKRTVAAPSVFIFPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 243) REGN14161 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAATACTAATGGTGGTAGC ACATTCTTCGCAGACTCCGTGAAGGGCCGTTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTACTG TGCGAAAGAAAAACGGGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCG TCTCCTCA (SEQ ID NO: 244) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTINTNGGSTF FADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCAKEKRGGMDVWGQGTTVTVSS (SEQ ID NO: 245) CDR1 DNA Sequence GGA TTC ACC TTT AGC AGC TAT GCC (SEQ ID NO: 156) CDR1 Amino Acid Sequence GFTFSSYA (SEQ ID NO: 100) CDR2 DNA Sequence ATT AAT ACT AAT GGT GGT AGC ACA (SEQ ID NO: 246) CDR2 Amino Acid Sequence I N T N G G S T (SEQ ID NO: 247) CDR3 DNA Sequence GCG AAA GAA AAA CGG GGC GGT ATG GAC GTC (SEQ ID NO: 248) CDR3 Amino Acid Sequence AKEKRGGMDV (SEQ ID NO: 249) LCVR DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATATGGCTCCAACAAAAAGAACTACTT AGCTTGGTACCAACAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGTAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATA TTATAGTACTCTCACGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 250) LCVR Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYGSNKKNYLAWYQQKPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTLTWTFGQGTKVEIK (SEQ ID NO: 251) CDR1 DNA Sequence CAG AGT GTT TTA TAT GGC TGC AAC AAA AAG AAC TAC (SEQ ID NO: 252) CDR1 Amino Acid Sequence QSVLYGSNKKNY (SEQ ID NO: 253) CDR2 DNA Sequence TGG GCA TOT (SEQ ID NO: 69) CDR2 Amino Acid Sequence WAS (SEQ ID NO: 70) CDR3 DNA Sequence CAG CAA TAT TAT AGT ACT CTC ACG TGG ACG (SEQ ID NO: 254) CDR3 Amino Acid Sequence QQYYSTLTWT (SEQ ID NO: 255) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGACCTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAATACTAATGGTGGTAGC ACATTCTTCGCAGACTCCGTGAAGGGCCGTTTCACCATCTCCAGAGACAATTCCAAGA ACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCATATATTACTG TGCGAAAGAAAAACGGGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCG TCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGA GCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAAC CGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCG GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCA GCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCA AGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCAC CACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCAT GATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACC CCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAA AGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC TGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCC TCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC AGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGA CCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATG GGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCT TCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCT TCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTC CCTGTCTCTGGGTAAATGA (SEQ ID NO: 256) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWVSTINTNGGSTF FADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCAKEKRGGMDVWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLF PPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF SCSVMHEALHN H YTQ KS LS LS LG K* (SEQ ID NO: 257) LC DNA Sequence GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCC ACCATCAACTGCAAGTCCAGCCAGAGTGTTTTATATGGCTCCAACAAAAAGAACTACTT AGCTTGGTACCAACAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTC ACTCTCACCATCAGTAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATA TTATAGTACTCTCACGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACT GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAA CTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTG GAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGA CAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTA CGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGT CACAAAGAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 258) LC Amino Acid Sequence DIVMTQSPDSLAVSLGERATINCKSSQSVLYGSNKKNYLAWYQQKPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTLTWTFGQGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 259) REG N14162 HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACCTGCACTGTTTCTGGTGACTCCATCAGTACTTACTACTGGAGCTGGATCCGG CAGCCCCCAGGAAAGGGACTGGAGTGGATTGGGTTTTTCCATTACAGTGGGAGCAGC AAATACAAGCCCTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAAGAATC AGTTCTCCCTGAACCTGCGGTCTGTGACCGCTGCGGACACGGCCGTGTATTATTGTGC GAGATTAGGCTGGGGATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC A (SEQ ID NO: 260) HCVR Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGDSISTYYWSWIRQPPGKGLEWIGFFHYSGSSKYK PSLKSRVTISLDTSKNQFSLNLRSVTAADTAVYYCARLGWGFDYWGQGTLVTVSS (SEQ ID NO: 261) CDR1 DNA Sequence GGT GAC TCC ATC AGT ACT TAC TAC (SEQ ID NO: 262) CDR1 Amino Acid Sequence G D S I S T Y Y (SEQ ID NO: 263) CDR2 DNA Sequence TTC CAT TAC AGT GGG AGC AGC (SEQ ID NO: 264) CDR2 Amino Acid Sequence F H Y S G S S (SEQ ID NO: 265) CDR3 DNA Sequence GCG AGA TTA GGC TGG GGA TTT GAC TAC (SEQ ID NO: 266) CDR3 Amino Acid Sequence ARLGWGFDY (SEQ ID NO: 267) LCVR DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAGCATT CACTTTCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 268) LCVR Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSAFTFGPGTKVDIK (SEQ ID NO: 269) CDR1 DNA Sequence CAG AGT GTT AGO AGC AAC TAC (SEQ ID NO: 270) CDR1 Amino Acid Sequence Q S V S S N Y (SEQ ID NO: 271) CDR2 DNA Sequence GGT GCA TOO (SEQ ID NO: 165) CDR2 Amino Acid Sequence GAS (SEQ ID NO: 90) CDR3 DNA Sequence CAG CAG TAT GGT AGC TCA GCA TTC ACT (SEQ ID NO: 272) CDR3 Amino Acid Sequence QQYGSSAFT (SEQ ID NO: 273) HC DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTC CCTCACCTGCACTGTTTCTGGTGACTCCATCAGTACTTACTACTGGAGCTGGATCCGG CAGCCCCCAGGAAAGGGACTGGAGTGGATTGGGTTTTTCCATTACAGTGGGAGCAGC AAATACAAGCCCTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAAGAATC AGTTCTCCCTGAACCTGCGGTCTGTGACCGCTGCGGACACGGCCGTGTATTATTGTGC GAGATTAGGCTGGGGATTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC AGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTC CGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTT GGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGA CAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGCACCACCTGT GGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCC CGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGT CCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCG GGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCA GGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTC CTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTA CACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCT GGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC TACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCTCCCTGTCTC TGGGTAAATGA (SEQ ID NO: 274) HC Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGDSISTYYWSWIRQPPGKGLEWIGFFHYSGSSKYK PSLKSRVTISLDTSKNQFSLNLRSVTAADTAVYYCARLGWGFDYWGQGTLVTVSSASTKG PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 275) LC DNA Sequence GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCA CCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTACTTAGCCTGGTACCAGCA GAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGG CATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGC AGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAGCATT CACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTC TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCT GCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTAC GCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGG GGAGAGTGTTAG (SEQ ID NO: 276) LC Amino Acid Sequence EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSAFTFGPGTKVDIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 277) REG N14163 HCVR DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAACTATTGGATGAACTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGA GAAGTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACT GTGCGAGACGTGGATACACCTATGGCAGCTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCA (SEQ ID NO: 278) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVANIKQDGSEK YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARRGYTYGSFDYWGQGTLVTV SS (SEQ ID NO: 279) CDR1 DNA Sequence GGA TTC ACC TTT AGT AAC TAT TGG (SEQ ID NO: 280) CDR1 Amino Acid Sequence GFTFSNYW (SEQ ID NO: 281) CDR2 DNA Sequence ATA AAG CAA GAT GGA AGT GAG AAG (SEQ ID NO: 282) CDR2 Amino Acid Sequence I K Q D G S E K (SEQ ID NO: 283) CDR3 DNA Sequence GCG AGA CGT GGA TAC ACC TAT GGC AGC TTT GAC TAG (SEQ ID NO: 284) CDR3 Amino Acid Sequence ARRGYTYGSFDY (SEQ ID NO: 285) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGTCGGGCGCGTCAGGGTTTTAGCATCTGGTTAGCCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATCCACTTTGCAGAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTACTTTTGTCAACAGGCTAACAGTTTCCCTCCCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAA (SEQ ID NO: 286) LCVR Amino Acid Sequence DIQMTQSPSSVSASVGDRVTITCRARQGFSIWLAWYQQKPGKAPKVLIYAASTLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPPTFGGGTKVEIK (SEQ ID NO: 287) CDR1 DNA Sequence CAG GGT TTT AGO ATO TGG (SEQ ID NO: 288) CDR1 Amino Acid Sequence Q G F S I W (SEQ ID NO: 289) CDR2 DNA Sequence GOT GCA TOC (SEQ ID NO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CAA CAG GCT AAC AGT TTC CCT CCC ACT (SEQ ID NO: 290) CDR3 Amino Acid Sequence QQANSFPPT (SEQ ID NO: 291) HC DNA Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAACTATTGGATGAACTGGGTCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGA GAAGTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAG AACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACT GTGCGAGACGTGGATACACCTATGGCAGCTTTGACTACTGGGGCCAGGGAACCCTGG TCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCT CCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCC CCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACC TTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGC CCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCC CAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACAC TCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGA AGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCAC CGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA AGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG CTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAA TGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCC CTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 292) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNVWRQAPGKGLEWVANIKQDGSEK YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARRGYTYGSFDYWGQGTLVTV SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPS VFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 293) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGTCGGGCGCGTCAGGGTTTTAGCATCTGGTTAGCCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATCCACTTTGCAGAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTACTTTTGTCAACAGGCTAACAGTTTCCCTCCCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTC ATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGG AGAGTGTTAG (SEQ ID NO: 294) LC Amino Acid Sequence DIQMTQSPSSVSASVGDRVTITCRARQGFSIWLAWYQQKPGKAPKVLIYAASTLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPPTFGGGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 295) REG N14164 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGTACTGGGTCCGC CAGGCTCCAGGCAAGGGTCTGGAGTGGGTGTCAATTATATCATATGATGGAAGTAATA AATACTATGCAGACTCCGTGAAGGGCCGATTCACCAGCTCCAGAGACAATTCCAAGAA CACGCTGTATCTTCAAATGAACAGCCTGAGAGGTGAGGACACGGCTGTGTATTACTGT GCGAAAGATAGAGGAGCTGGAACTACAGCCTTCCACTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 296) HCVR Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEWVSIISYDGSNKY YADSVKGRFTSSRDNSKNTLYLQMNSLRGEDTAVYYCAKDRGAGTTAFHYGMDVWGQG TTVTVSS (SEQ ID NO: 297) CDR1 DNA Sequence GGA TTC ACC TTC AGT AAC TAT GGC (SEQ ID NO: 298) CDR1 Amino Acid Sequence GFTFSNYG (SEQ ID NO: 299) CDR2 DNA Sequence ATA TCA TAT GAT GGA AGT AAT AAA (SEQ ID NO: 300) CDR2 Amino Acid Sequence I S Y D G S N K (SEQ ID NO: 193) CDR3 DNA Sequence GCG AAA GAT AGA GGA GCT GGA ACT ACA GCC TTC CAC TAC GGT ATG GAC GTC (SEQ ID NO: 301) CDR3 Amino Acid Sequence AKDRGAGTTAFHYGMDV (SEQ ID NO: 302) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGTTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATTCAGTTTGCAAAGTGGGGTCC CTTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTAACTATCAGTAGCCT GCAACCTGAGGATTTCGCAACTTACTATTGTCACCAGACTTATAGTGTTCCTCCGATCA CCTTCGGCCAAGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 303) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKVLIYAAFSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCHQTYSVPPITFGQGTKLEIK (SEQ ID NO: 304) CDR1 DNA Sequence CAG AGC ATT AGC AGT TAT (SEQ ID NO: 305) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GCT GCA TTC (SEQ ID NO: 306) CDR2 Amino Acid Sequence A A F (SEQ ID NO: 307) CDR3 DNA Sequence CAC CAG ACT TAT AGT GTT CCT CCG ATC ACC (SEQ ID NO: 308) CDR3 Amino Acid Sequence HQTYSVPPIT (SEQ ID NO: 309) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAACTATGGCATGTACTGGGTCCGC CAGGCTCCAGGCAAGGGTCTGGAGTGGGTGTCAATTATATCATATGATGGAAGTAATA AATACTATGCAGACTCCGTGAAGGGCCGATTCACCAGCTCCAGAGACAATTCCAAGAA CACGCTGTATCTTCAAATGAACAGCCTGAGAGGTGAGGACACGGCTGTGTATTACTGT GCGAAAGATAGAGGAGCTGGAACTACAGCCTTCCACTACGGTATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCC CTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGT CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGA TCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCA TGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCA AAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAG GGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAG GTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 310) HC Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEVWSIISYDGSNKY YADSVKGRFTSSRDNSKNTLYLQMNSLRGEDTAVYYCAKDRGAGTTAFHYGMDVWGQG TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 311) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGTTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGGTCCTGATCTATGCTGCATTCAGTTTGCAAAGTGGGGTCC CTTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTAACTATCAGTAGCCT GCAACCTGAGGATTTCGCAACTTACTATTGTCACCAGACTTATAGTGTTCCTCCGATCA CCTTCGGCCAAGGGACCAAGCTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG GAGAGTGTTAG (SEQ ID NO: 312) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKVLIYAAFSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCHQTYSVPPITFGQGTKLEIKRTVAAPSVFIFPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 313) REG N14165 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAACTATGGAATCAGCTGGATACGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACAC AAACTATGCACAGAAGGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTATATTTCTGT GCGAGAGATCGGGGACAACTGGATCGAGGAGGAAACTACTACTTCTACATTATGAGCG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 314) HCVR Amino Acid Sequence QVQLVQSGGEVKKPGASVKVSCKASGYTFTNYGISWIRQAPGQGLEWMGWISAYNGNTN YAQKVQGRVTMTTDTSTTTAYMELRSLRSDDTAVYFCARDRGQLDRGGNYYFYIMSVWG QGTTVTVSS (SEQ ID NO: 315) CDR1 DNA Sequence GGT TAC ACC TTT ACC AAC TAT GGA (SEQ ID NO: 316) CDR1 Amino Acid Sequence GYTFTNYG (SEQ ID NO: 317) CDR2 DNA Sequence ATC AGC GCT TAC AAT GGT AAC ACA (SEQ ID NO: 318) CDR2 Amino Acid Sequence I S A Y N G N T (SEQ ID NO: 319) CDR3 DNA Sequence GOG AGA GAT OGG GGA CAA CTG GAT OGA GGA GGA AAC TAO TAC TTC TAG ATT ATG AGO GTC (SEQ ID NO: 320) CDR3 Amino Acid Sequence ARDRGQLDRGGNYYFYIMSV (SEQ ID NO: 321) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTAATCTATGCTGCATCCAATTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAGTAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA (SEQ ID NO: 322) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPWTFGQGTKVEIK (SEQ ID NO: 323) CDR1 DNA Sequence CAG GAC ATT AGA AAT GAT (SEQ ID NO: 11) CDR1 Amino Acid Sequence Q D I R N D (SEQIDNO: 12) CDR2 DNA Sequence GCT GCA TGC (SEQIDNO: 13) CDR2 Amino Acid Sequence A A S (SEQ ID NO: 14) CDR3 DNA Sequence CTA CAG CAT AGT AGT TAC CCG TGG ACG (SEQ ID NO: 324) CDR3 Amino Acid Sequence LQHSSYPWT (SEQ ID NO: 325) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAGGTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAG GTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAACTATGGAATCAGCTGGATACGACA GGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACAC AAACTATGCACAGAAGGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAC CACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTATATTTCTGT GCGAGAGATCGGGGACAACTGGATCGAGGAGGAAACTACTACTTCTACATTATGAGCG TCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGG TCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCT GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT CCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTGTTC CCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAG CCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAG ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAAG AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC AACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 326) HC Amino Acid Sequence QVQLVQSGGEVKKPGASVKVSCKASGYTFTNYGISWIRQAPGQGLEWMGWISAYNGNTN YAQKVQGRVTMTTDTSTTTAYMELRSLRSDDTAVYFCARDRGQLDRGGNYYFYIMSVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVD KSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 327) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGGACATTAGAAATGATTTAGGCTGGTATCAGCAGAA ACCAGGGAAAGCCCCTAAGCGCCTAATCTATGCTGCATCCAATTTGCAAAGTGGGGTC CCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCC TGCAGCCTGAAGATTTTGCAACTTATTACTGTCTACAGCATAGTAGTTACCCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 328) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASNLQSGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPWTFGQGTKVEIKRTVAAPSVFIFPPSD EQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 329) REG N14175 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCAGATTCAGTAGTTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTCATTTCATATGATGGAAGTGAT AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGA ACACGCTTTATATGCAAATGAACAGACTGAAAAGTGAGGACACGGCTGTTTATTATTGT GCGAAAGAGAGAAGTACAGCAGCTCGTCGGGGGGACTACTACGACTACGGTATGGAC GTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 330) HCVR Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFRFSSYGMHWVRQAPGKGLEWVAVISYDGSDK YYADSVKGRFTISRDNSKNTLYMQMNRLKSEDTAVYYCAKERSTAARRGDYYDYGMDVW GQGTTVTVSS (SEQ ID NO: 331) CDR1 DNA Sequence GGA TTC AGA TTC AGT AGT TAT GGC (SEQ ID NO: 332) CDR1 Amino Acid Sequence GFRFSSYG (SEQ ID NO: 333) CDR2 DNA Sequence ATT TCA TAT GAT GGA AGT GAT AAA (SEQ ID NO: 334) CDR2 Amino Acid Sequence I S Y D G S D K (SEQ ID NO: 335) CDR3 DNA Sequence GCG AAA GAG AGA AGT ACA GCA GOT CGT CGG GGG GAC TAC TAC GAC TAC GGT ATG GAC GTC (SEQ ID NO: 336) CDR3 Amino Acid Sequence AKERSTAARRGDYYDYGMDV (SEQ ID NO: 337) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTTTGCATCTGTGGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCACCAGAAA CCAGGGAGAGCCCCTAAACTCCTGATCTTTGCTTCATTCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGT GGAACCTGAAGATTTTGCATCTTACTACTGTCAACAGAGTTACAGTACCCCATTCACTT TCGGCCCTGGGACCAAAGTGGATATCAAA (SEQ ID NO: 338) LCVR Amino Acid Sequence DIQMTQSPSSLFASVGDRVTITCRASQSISSYLNWYHQKPGRAPKLLIFASFSLQSGVPSRF SGSGSGTDFTLTISSVEPEDFASYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 339) CDR1 DNA Sequence CAG AGC ATT AGC AGC TAT (SEQ ID NO: 236) CDR1 Amino Acid Sequence Q S I S S Y (SEQ ID NO: 237) CDR2 DNA Sequence GOT TCA TTC (SEQ ID NO: 340) CDR2 Amino Acid Sequence ASF (SEQ ID NO: 341) CDR3 DNA Sequence CAA CAG AGT TAC AGT ACC CCA TTC ACT (SEQ ID NO: 342) CDR3 Amino Acid Sequence QQSYSTPFT (SEQ ID NO: 343) HC DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCAGATTCAGTAGTTATGGCATGCACTGGGTCCGC CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTCATTTCATATGATGGAAGTGAT AAATATTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGA ACACGCTTTATATGCAAATGAACAGACTGAAAAGTGAGGACACGGCTGTTTATTATTGT GCGAAAGAGAGAAGTACAGCAGCTCGTCGGGGGGACTACTACGACTACGGTATGGAC GTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCG GTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG CTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGC CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTC CCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTG CAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATAT GGTCCCCCATGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCATCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCG TGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATG GCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGT ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAA AGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGG AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCG ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTCACCGTGGACAA GAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCA CAACCACTACACACAGAAGTCCCTCTCCCTGTCTCTGGGTAAATGA (SEQ ID NO: 344) HC Amino Acid Sequence QVQLVESGGGWQPGRSLRLSCAASGFRFSSYGMHWVRQAPGKGLEWVAVISYDGSDK YYADSVKGRFTISRDNSKNTLYMQMNRLKSEDTAVYYCAKERSTAARRGDYYDYGMDVW GQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP APPVAGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKP REEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLP PSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTV DKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 345) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTTTGCATCTGTGGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCACCAGAAA CCAGGGAGAGCCCCTAAACTCCTGATCTTTGCTTCATTCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGT GGAACCTGAAGATTTTGCATCTTACTACTGTCAACAGAGTTACAGTACCCCATTCACTT TCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCATCTGTCTTCAT CTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAAT CGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCC TCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCT GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG AGTGTTAG (SEQ ID NO: 346) LC Amino Acid Sequence DIQMTQSPSSLFASVGDRVTITCRASQSISSYLNWYHQKPGRAPKLLIFASFSLQSGVPSRF SGSGSGTDFTLTISSVEPEDFASYYCQQSYSTPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 347) REGN14176 HCVR DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAACTGAGGTGAAGAAGCCTGGGGCCTCAGTGACG GTCTCCTGCAAGGCTTCTGGTTACACTTTTACCAGCTATAGTGTCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACGCTTACAATGGTGACA CAAACTATGCACAGAGGTTCCACGGCAGAGTCACCATGACCACAGACACATCCACGAG CACAGCCTATATGGACTTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATCGGATAAGTGGAACCTTAGACTACTGGGGCCAGGGAACCCTGGTCACC GTCTCCTCA (SEQ ID NO: 348) HCVR Amino Acid Sequence QVQLVQSGTEVKKPGASVTVSCKASGYTFTSYSVSWVRQAPGQGLEWMGWINAYNGDT NYAQRFHGRVTMTTDTSTSTAYMDLRSLRSDDTAVYYCARDRISGTLDYWGQGTLVTVSS (SEQ ID NO: 349) CDR1 DNA Sequence GGT TAC ACT TTT ACC AGC TAT AGT (SEQ ID NO: 350) CDR1 Amino Acid Sequence GYTFTSYS (SEQ ID NO: 351) CDR2 DNA Sequence ATC AAC GCT TAC AAT GGT GAC ACA (SEQ ID NO: 352) CDR2 Amino Acid Sequence I N A Y N G D T (SEQ ID NO: 353) CDR3 DNA Sequence GCG AGA GAT CGG ATA AGT GGA ACC TTA GAC TAC (SEQ ID NO: 354) CDR3 Amino Acid Sequence ARDRISGTLDY (SEQ ID NO: 355) LCVR DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGTCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTAATGGAAACACCTACTTGAAT TGGTTTCAGCAGAGGCCAGGCCAATCTCCACGGCGCCTATTTTATAAGGTTTCTAACC GGGACTCTGGGGTCCCAGACAGATTCAGCGGCATTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGATTTTATTACTGCATGCAAGGTAC ACACTGGCCTCGGACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 356) LCVR Amino Acid Sequence DWMTQSPLSLPVTLGQSASISCRSSQSLVYSNGNTYLNWFQQRPGQSPRRLFYKVSNR DSGVPDRFSGIGSGTDFTLKISRVEAEDVGFYYCMQGTHWPRTFGQGTKLEIK (SEQ ID NO: 357) CDR1 DNA Sequence CAA AGO CTC GTA TAG AGT AAT GGA AAC ACC TAC (SEQ ID NO: 358) CDR1 Amino Acid Sequence QSLVYSNGNTY (SEQ ID NO: 359) CDR2 DNA Sequence AAG GTT TCT (SEQ ID NO: 360) CDR2 Amino Acid Sequence K V S (SEQ ID NO: 361) CDR3 DNA Sequence ATG CAA GGT ACA CAC TGG CCT CGG ACT (SEQ ID NO: 362) CDR3 Amino Acid Sequence MQGTHWPRT (SEQ ID NO: 363) HC DNA Sequence CAGGTTCAGCTGGTGCAGTCTGGAACTGAGGTGAAGAAGCCTGGGGCCTCAGTGACG GTCTCCTGCAAGGCTTCTGGTTACACTTTTACCAGCTATAGTGTCAGCTGGGTGCGAC AGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACGCTTACAATGGTGACA CAAACTATGCACAGAGGTTCCACGGCAGAGTCACCATGACCACAGACACATCCACGAG CACAGCCTATATGGACTTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATCGGATAAGTGGAACCTTAGACTACTGGGGCCAGGGAACCCTGGTCACC GTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGG AGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACAC CAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCGTGCCCAGC ACCACCTGTGGCAGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCA CAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTG ACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAAT GGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC TTCTTCCTCTACAGCAGGCTCACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGTCCCTCT CCCTGTCTCTGGGTAAATGA (SEQ ID NO: 364) HC Amino Acid Sequence QVQLVQSGTEVKKPGASVTVSCKASGYTFTSYSVSWVRQAPGQGLEWMGWINAYNGDT NYAQRFHGRVTMTTDTSTSTAYMDLRSLRSDDTAVYYCARDRISGTLDYWGQGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLGK* (SEQ ID NO: 365) LC DNA Sequence GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGTCGGCCT CCATCTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTAATGGAAACACCTACTTGAAT TGGTTTCAGCAGAGGCCAGGCCAATCTCCACGGCGCCTATTTTATAAGGTTTCTAACC GGGACTCTGGGGTCCCAGACAGATTCAGCGGCATTGGGTCAGGCACTGATTTCACAC TGAAAATCAGCAGGGTGGAGGCTGAGGATGTTGGATTTTATTACTGCATGCAAGGTAC ACACTGGCCTCGGACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGC TGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGT GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA ACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA GAGCTTCAACAGGGGAGAGTGTTAG (SEQ ID NO: 366) LC Amino Acid Sequence DWMTQSPLSLPVTLGQSASISCRSSQSLVYSNGNTYLNWFQQRPGQSPRRLFYKVSNR DSGVPDRFSGIGSGTDFTLKISRVEAEDVGFYYCMQGTHWPRTFGQGTKLEIKRTVAAPS VFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 367) REG N14177 HCVR DNA Sequence CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAG ACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGCGACTATTACATGAGCTGGATCCGC CAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATCAGTAAAAGTGGTACTACC AAATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGA ACTCAGTGTATCTGCAAATGAACAGTTTGAGAGCCGAGGACACGGCCGTCTATTACTG TGAGAAAAGGGGCAGCTTGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 368) HCVR Amino Acid Sequence QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISKSGTTKYY ADSVKGRFTISRDNAKNSVYLQMNSLRAEDTAVYYCEKRGSLGQGTLVTVSS (SEQ ID NO: 369) CDR1 DNA Sequence GGA TTC ACC TTC AGC GAC TAT TAC (SEQ ID NO: 370) CDR1 Amino Acid Sequence GFTFSDYY (SEQ ID NO: 371) CDR2 DNA Sequence ATC AGT AAA AGT GGT ACT ACC AAA (SEQ ID NO: 372) CDR2 Amino Acid Sequence I S K S G T T K (SEQ ID NO: 373) CDR3 DNA Sequence GAG AAA AGG GGC AGC (SEQ ID NO: 374) CDR3 Amino Acid Sequence E K R G S (SEQ ID NO: 375) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCAGGCGAGTCAGGACATTAGCAAGTATTTAAATTGGTATCAGCAGAA GCCAGGGAAAGCCCCTAAGCTCCTGATCTACGGTGCATCCTATTTGGAAACAGGGGTC CCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTTACCATCAGCAGCCT GCAGCCTGAAGATATTGCAACATATTTCTGTCAACAATATGATATTGTCCGGTTCACTTT TGGCCAGGGGACCAAGCTGGAGATCAAA (SEQ ID NO: 376) LCV...

Claims

1. An antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR), wherein the antigen-binding protein exhibits less than 50% inhibition of an activity of the extracellular domain of human p75NTR, wherein the activity of the extracellular domain of p75NTR is the blocking of human nerve growth factor (NGF)-dependent activation of human tropomyosin receptor kinase A (TrkA) signaling, as measured in a cell-based assay.

2. The antigen-binding protein of claim 1, wherein the cell-based assay comprises the steps of:a) incubating a soluble extracellular domain of human p75NTR with mature human NGF in the presence of the antigen-binding protein, optionally the extracellular domain of human p75NTR is fused to an Fc domain of IgG,b) incubating the mixture of step (a) with a population of recombinant mammalian cells which stably expresses TrkA and a serum response element fused to a luciferase reporter.c) measuring luciferase activity in Relative Luminescence Units (RLU) from the mixture of step (b), andd) calculating % inhibition using the formula100 X RLUantigen—binding protein    RLUsoiub]e pygRLUnqf — RLUsoluble pygwherein, RLUsoiubie P75 is the RLU value from cells treated under the same conditions with an antigen-binding protein which does not bind to p75NTR, and RLUngf is the RLU value from cells treated with only the human mature NGF in the absence of the soluble extracellular domain of p75NTR.

3. The antigen-binding protein of claim 1 or claim 2, which comprises:(1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof;(2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVRcomprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof;(3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof;(4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or(5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

4. The antigen-binding protein of any one of claims 1-3, which comprises:(1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof;(2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof;(3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof;(4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof; and / or(5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof.

5. The antigen-binding protein of any one of claims 1-4, which comprises:(1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof;(2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof;(3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof;(4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or(5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

6. The antigen-binding protein of any one of claims 1-5, which comprises:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof;(2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof;(3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof;(4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and / or(5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof.

7. An antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR),comprising:(i) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 58, 78, 98, 116, 136, 155, 173, 189, 207, 227, 245, 261,279, 297, 315, 331, 349, 369, 387, 401, 417, 427, 437, 445, 455, 465, 475, 484, 493, 503, 513, 519, 529, 549, 569, 589 or 609, or a variant thereof; and / or(ii) a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, 30, 50, 66, 86, 106, 124, 144, 162, 179, 197, 215, 235, 251,269, 287, 304, 323, 339, 357, 377, 391, 409, 537, 557, 577, or 597, or a variant thereof.

8. The antigen-binding protein of claim 7 which comprises:(1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof;(2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof;(4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof;(5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof;(7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVRcomprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof;(8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof;(10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof;(11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof;(12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof;(13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof;(14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof;(15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and aLCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof;(17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof;(18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof;(19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof;(20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof;(21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof;(22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof;(23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and aLCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(29) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(30) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(31) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and aLCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(32) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(33) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(34) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(35) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(36) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof;(37) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof;(38) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof;(39) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and aLCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or(40) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

9. The antigen-binding protein of claim 7 or claim 8 which comprises:(1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof;(2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof;(4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof;(5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof;(7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof;(8) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(9) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof;(10) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof;(11) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof;(12) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof;(13) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof;(14) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof;(15) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof;(16) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof;(17) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof;(18) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(19) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(20) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(21) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(22) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(23) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(24) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(25) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(26) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(27) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or(28) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

10. The antigen-binding protein of claim 7 or claim 8 which comprises:(1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof;(2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVRcomprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof;(3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof;(5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof;(6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or(7) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

11. The antigen-binding protein of claim 7 or claim 8 which comprises:(1) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(2) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(3) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(4) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(5) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and / or(6) a HCVR comprising the HCDR1, HCDR2 and HCDR3 of a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR comprising the LCDR1, LCDR2 and LCDR3 of a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

12. The antigen-binding protein of claim 7 or claim 8 which comprises:(1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof;(2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof;(3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof;(4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof;(5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof;(6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof;(7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof;(8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140, or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof;(9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof;(10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof;(11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof;(12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof;(13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof;(14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof;(15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof;(16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; anda LCVR that comprises: an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof;(17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof;(18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof;(19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof;(20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof;(21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof;(22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof;(23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(29) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(30) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(31) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; anda LCVR that comprises: LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(32) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(33) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(34) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(35) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(36) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 531, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 533 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 535, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 539, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 541, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 543, or a variant thereof;(37) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 551, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 553 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 555, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 559, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 561, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 563, or a variant thereof;(38) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 571, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 573 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 575, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 579, or a variant thereof, a LCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 581, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 583, or a variant thereof;(39) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 591, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 593 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 595, or a variant thereof; anda LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof;(40) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 611, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 613 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 615, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 599, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 601, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 603, or a variant thereof.

13. The antigen-binding protein of any one of claims 7-9 which comprises:(1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16, or a variant thereof;(2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof;(3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 48, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 52, or a variant thereof;(4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 60, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 64, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 68, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, or a variant thereof;(5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof;(6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 102 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 104, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 108, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 110, or a variant thereof;(7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 122, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 126, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 128, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 130, or a variant thereof;(8) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof;(9) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 160, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 164, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 167, or a variant thereof;(10) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 175 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 177, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 181, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 183, or a variant thereof;(11) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 209, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 211 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 213, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 217, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 219, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 221, or a variant thereof;(12) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 100, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 247 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 249, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 253, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 70, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 255, or a variant thereof;(13) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 281, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 285, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 289, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 291, or a variant thereof;(14) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 299, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 302, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 307, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 309, or a variant thereof;(15) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 317, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 321, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, ora variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 325, or a variant thereof;(16) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 351, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 353 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 355, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 359, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 363, or a variant thereof;(17) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 389, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 393, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 361, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 395, or a variant thereof;(18) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 419, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 421 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 423, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(19) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 429, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 431 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 433, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(20) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 441, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(21) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 447, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 449 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 451, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(22) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 457, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 459 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 461, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(23) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 467, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 469 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 471, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(24) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 477, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 158 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 480, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(25) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 495, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 497 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 499, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(26) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 505, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 507 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 509, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof;(27) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 319 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 515, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and / or(28) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 521, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 523 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 525, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

14. The antigen-binding protein of any one of claims 7-8 and 10 which comprises(1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 191, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 193 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 195, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 199, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 201, or a variant thereof;(2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 229, or a variant thereof, a HCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 231 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 233, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 239, or a variant thereof;(3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof;(4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 333, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 335 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 337, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 341, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 343, or a variant thereof;(5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof;(6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 403, or a variant thereof, a HCDR2 comprising the amino acid sequence setforth in SEQ ID NO: 405 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 407, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof; and / or(7) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

15. The antigen-binding protein of any one of claims 7-8 and 11 which comprises:(1) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 28, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 32, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 34, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36, or a variant thereof;(2) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 84, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 88, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 92, or a variant thereof;(3) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 138, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 140 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 142, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 146, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 149, or a variant thereof;(4) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 263, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 265 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 267, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 271, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 273, or a variant thereof;(5) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 371, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 373 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 375, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 379, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 90, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 381, or a variant thereof; and / or(6) a HCVR that comprises: a HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 486, or a variant thereof, a HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 283 or a variant thereof, and a HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 489, or a variant thereof; and / ora LCVR that comprises: a LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 237, or a variant thereof, a LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 14, or a variant thereof, and a LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 411, or a variant thereof.

16. The antigen-binding protein of any one of claims 7-8 and 12 which comprises:(1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof;(2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof;(4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof;(5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof;(7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof;(8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof;(10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof;(11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof;(12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof;(13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof;(14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof;(15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof;(17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof;(18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof;(19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof;(20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof;(21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof;(22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof;(23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(29) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(30) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(31) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(32) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(33) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(34) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(35) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(36) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 529, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 537, or a variant thereof;(37) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 549, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 557, or a variant thereof;(38) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 569, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 577, or a variant thereof;(39) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 589, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof; and / or(40) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 609, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 597, or a variant thereof.

17. The antigen-binding protein of any one of claims 7-9, 12-13, and 16, which comprises:(1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 2, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof;(2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 42, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 50, or a variant thereof;(4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 58, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 66, or a variant thereof;(5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 98, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 106, or a variant thereof;(7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 116, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 124, or a variant thereof;(8) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(9) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 155, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 162, or a variant thereof;(10) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 173, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 179, or a variant thereof;(11) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 207, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 215, or a variant thereof;(12) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 245, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 251, or a variant thereof;(13) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 279, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 287, or a variant thereof;(14) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 297, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 304, or a variant thereof;(15) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 315, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 323, or a variant thereof;(16) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 349, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 357, or a variant thereof;(17) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 387, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 391, or a variant thereof;(18) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 417, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(19) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 427, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(20) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 437, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(21) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 445, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(22) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 455, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(23) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 465, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(24) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 475, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(25) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 493, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(26) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 503, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof;(27) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 513, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or28) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 519, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

18. The antigen-binding protein of any one of claims 7-8, 10, 12, 14, and 16, which comprises:(1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 189, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 197, or a variant thereof;(2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 227, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 235, or a variant thereof;(3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 331, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 339, or a variant thereof;(5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof;(6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 401, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof; and / or(7) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

19. The antigen-binding protein of any one of claims 7-8, 11, 12, 15, and 16, which comprises:(1) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 22, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 30, or a variant thereof;(2) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 78, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 86, or a variant thereof;(3) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 136, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 144, or a variant thereof;(4) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 261, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 269, or a variant thereof;(5) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 369, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 377, or a variant thereof; and / or(6) a HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 484, or a variant thereof; and a LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 409, or a variant thereof.

20. The antigen-binding protein of any one of claims 7-8, 12, and 16, which comprises:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof;(2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof;(3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof;(4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof;(5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof;(6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof;(7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof;(8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof;(9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof;(10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof;(11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof;(12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof;(13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof;(14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof;(15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof;(16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof;(17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof;(18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof;(19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof;(20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof;(21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof;(22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof;(23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(29) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(30) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(31) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(32) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(33) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(34) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(35) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(36) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 545, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 547, or a variant thereof;(37) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 565, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 567, or a variant thereof;(38) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 585, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 587, or a variant thereof;(39) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 605, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof; and / or(40) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 617, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 607, or a variant thereof.

21. The antigen-binding protein of any one of claims 7-9, 12-13, 16-17, and 20, which comprises:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 18, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 20, or a variant thereof;(2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof;(3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 54, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 56, or a variant thereof;(4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 74, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 76, or a variant thereof;(5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof;(6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 112, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 114, or a variant thereof;(7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 132, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 134, or a variant thereof;(8) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof;(9) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 169, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 171, or a variant thereof;(10) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 185, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 187, or a variant thereof;(11) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 223, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 225, or a variant thereof;(12) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 257, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 259, or a variant thereof;(13) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 293, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 295, or a variant thereof;(14) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 311, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 313, or a variant thereof;(15) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 327, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 329, or a variant thereof;(16) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 365, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 367, or a variant thereof;(17) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 397, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 399, or a variant thereof;(18) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 425, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(19) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 435, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(20) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 443, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(21) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 453, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(22) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 463, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(23) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 473, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(24) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 482, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(25) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 501, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(26) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof;(27) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 517, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and / or(28) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 527, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

22. The antigen-binding protein of any one of claims 7-8, 10, 12, 14, 16, 18, and 20, which comprises:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 203, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 205, or a variant thereof;(2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 241, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 243, or a variant thereof;(3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof;(4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 345, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 347, or a variant thereof;(5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof;(6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 413, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof; and / or(7) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

23. The antigen-binding protein of any one of claims 7-8, 11, 12, 15, 16, 19, and 20, which comprises:(1) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 38, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 40, or a variant thereof;(2) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 94, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 96, or a variant thereof;(3) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 151, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 153, or a variant thereof;(4) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 275, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 277, or a variant thereof;(5) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 383, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 385, or a variant thereof; and / or(6) a heavy chain that comprises the amino acid sequence set forth in SEQ ID NO: 491, or a variant thereof, and a light chain that comprises the amino acid sequence set forth in SEQ ID NO: 415, or a variant thereof.

24. The antigen binding protein of any one of claims 7-9, 12-13, 16-17, and 20-21, wherein the antigen-binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by at least about 50%.

25. The antigen binding protein of claims 7-8, 10, 12, 14, 16, 18, 20, and 22, wherein the antigen-binding protein blocks the binding of a human neurotrophin receptor mouse Fc dimer (human p75-mFc) to human neurotrophin 3 (hNT-3) by less than about 50%.

26. An antigen-binding protein that binds to the same epitope on p75NTR as an antibody comprising an HCVR / LCVR amino acid sequence pair as set forth in Table 1-1.

27. An antigen-binding protein that competes for binding to p75NTR with an antibody comprising an HCVR / LCVR amino acid sequence pair as set forth in Table 1-1.

28. The antigen-binding protein of any one of claims 1-27, wherein the antigen-binding protein comprises an antibody or antigen-binding fragment thereof.

29. The antigen-binding protein of any one of claims 1-27, wherein the antigen-binding protein is selected from a humanized antibody or antigen binding fragment thereof, human antibody or antigen binding fragment thereof, murine antibody or antigen binding fragment thereof, chimeric antibody or antigen binding fragment thereof, monovalent Fab', divalent Fab2, F(ab)'3 fragments, single-chain fragment variable (scFv), bis-scFv, (scFv)2, diabody, minibody, nanobody, triabody, tetrabody, disulfide stabilized Fv protein (dsFv), single-domain antibody (sdAb), Ig NAR, single heavy chain antibody, bispecific antibody or biding fragment thereof, bi-specific T-cell engager (BiTE), trispecific antibody, or chemically modified derivatives thereof.

30. The antigen-binding protein of claim 29, wherein the antigen-binding protein comprises a fragment antigen-binding region (Fab).

31. The antigen-binding protein of claim 29, wherein the antigen-binding protein comprises a single chain fragment variable (scFv).

32. The antigen-binding protein of claim 31, wherein the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: HCVR-LCVR.

33. The antigen-binding protein of claim 31, wherein the scFv comprises variable regions arranged in the following orientation from N-terminus to C-terminus: LCVR-HCVR.

34. The antigen-binding protein of any one of claims 31-33, wherein the variable regions in the scFv are connected by a linker.

35. The antigen-binding protein of claim 34, wherein the linker is a peptide linker.

36. The antigen-binding protein of claim 35, wherein the peptide linker is -(GGGGS)n-(SEQ ID NO: 668), wherein n is any integral selected from 1-10.

37. The antigen-binding protein of any one of claims 1-36, wherein the antigen-binding protein binds to human p75NTR.

38. The antigen-binding protein of claim 37, wherein the antigen-binding protein binds to human p75NTR with a KD of about 1X10-9 M or a stronger affinity.

39. An isolated polynucleotide encoding the antigen-binding protein of any one of claims 1-38.

40. A vector comprising the isolated polynucleotide of claims 39.

41. A host cell comprising the antigen-binding protein of any one of claims 1 -38, the isolated polynucleotide of claim 39 or the vector of claim 40.

42. The host cell of claim 41 which is a Chinese hamster ovary (CHO) cell.

43. A protein-drug conjugate comprising an antigen-binding protein that binds to p75 neurotrophin receptor (p75NTR) and is conjugated to a molecular cargo.

44. The protein-drug conjugate of claim 43, wherein the antigen-binding protein comprises the antigen-binding protein of any one of claims 1-38.

45. The protein-drug conjugate of claim 43 or claim 44, wherein the antigen-binding protein and the molecular cargo are conjugated via a linker.

46. The protein-drug conjugate of any one of claims 43-45, wherein the molecular cargo comprises a polynucleotide molecule, a polypeptide molecule, a carrier, or a small molecule.

47. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a polynucleotide molecule.

48. The protein-drug conjugate of claim 47, wherein the polynucleotide molecule is an interfering nucleic acid molecule, a guide RNA, a ribozyme, an aptamer, a mixmer, a multimer, or an mRNA.

49. The protein-drug conjugate of claim 48, wherein the interfering nucleic acid molecule is an siRNA, an shRNA, a miRNA, an antisense oligonucleotide, ora gapmer.

50. The protein-drug conjugate of claim 49, wherein the interfering nucleic acid molecule is an siRNA.

51. The protein-drug conjugate of claim 50, wherein the siRNA comprises a sense strand of 21 nucleotides in length.

52. The protein-drug conjugate of claim 50 or claim 51, wherein the siRNA comprises an antisense strand of 23 nucleotides in length.

53. The protein-drug conjugate of any one of claims 50-52, wherein the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 5’ end of the sense strand.

54. The protein-drug conjugate of any one of claims 50-53, wherein the siRNA comprises two phosphorothioate linkages at the first and second internucleoside linkages at the 3’ and / or 5’ ends of the antisense strand.

55. The protein-drug conjugate of claim 49, wherein the interfering nucleic acid molecule is an antisense oligonucleotide.

56. The protein-drug conjugate of claim 48, wherein the polynucleotide molecule is a guide RNA.

57. The protein-drug conjugate of any one of claims 46-56, wherein the polynucleotide molecule targets a gene or gene product associated with pain, itch, or a neurological disease or disorder.

58. The protein-drug conjugate of claim 57, wherein the gene or gene product associated with pain, itch, or a neurological disease or disorder is voltage-gated sodium channel Nav1.7, voltage-gated sodium channel Nav1.8, voltage-gated sodium channel Nav1.9, voltage-gated sodium channel Navi.6, tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase C (TRKC), acid-sensing ion channel subunit 1 (ASIC1), acid-sensing ion channel subunit 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1), transient receptor potential vanilloid 4 (TRPV4), transient receptor potential cation channel, subfamily A, member 1 (TRPA1), transient receptor potential cation channel subfamily M, member 8 (TRPM8), fatty acid amide hydrolase (FAAH), piezo type mechanosensitive ion channel component 1 (PIEZ01), piezo type mechanosensitive ion channel component 2 (PIEZ02), enkephalin, RET proto-oncogene (RET), interleukin 4 receptor (IL4R), interleukin 13 receptor (IL13R), interleukin 31 receptor (IL31R), interleukin 6 receptor alpha (IL6Ra), glycoprotein 130(gp130), FXYD domain containing ion transport regulator 2 (FXYD2), P2X purinoceptor 3 (P2X3), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), or interleukin 6 (IL6).

59. The protein-drug conjugate of any one of claims 46-58, wherein the polynucleotide molecule comprises one or more modified nucleotides.

60. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a polypeptide molecule.

61. The protein-drug conjugate of claim 60, wherein the polypeptide molecule is an enzyme, a neuroprotective molecule, or an antigen-binding protein that binds to a target other than p75NTR.

62. The protein-drug conjugate of claim 60 or claim 61, wherein the polypeptide molecule is associated with pain, itch, or a neurological disease or disorder.

63. The protein-drug conjugate of claim 62, wherein the polypeptide molecule is a neurotrophic factor, an antibody or antibody fragment, an antibody receptor fusion protein, or a suppressor of cytokine signaling.

64. The protein-drug conjugate of any one of claims 43-63 for use in treating or preventing pain, itch, or a neurological disease or disorder.

65. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic postoperative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporomandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS).

66. The protein-drug conjugate of claim 65, wherein the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia.

67. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the itch is chronic itch.

68. The protein-drug conjugate of any one of claims 57-58 and 62-64, wherein the neurological disease or disorder is a neurodegenerative disease or disorder, a neurodevelopmental disease or disorder, a physical injury, a neuropsychiatric disease or disorder, or a neurological cancer.

69. The protein-drug conjugate of claim 68, wherein the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

70. The protein-drug conjugate of claim 68, wherein the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema.

71. The protein-drug conjugate of claim 68, wherein the neurological cancer is a brain cancer or a peripheral nerve cancer.

72. The protein-drug conjugate of any one of claims 57-71, wherein the pain, itch, or neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell or a trigeminal ganglion cell, or a population thereof.

73. The protein-drug conjugate of claim 46, wherein the molecular cargo comprises a carrier.

74. The protein-drug conjugate of claim 73, wherein the carrier is a lipid-based carrier.

75. The protein-drug conjugate of claim 74, wherein the lipid-based carrier is a lipidnanoparticle (LNP), a liposome, a lipidoid, ora lipoplex.

76. The protein-drug conjugate of claim 75, wherein the lipid-based carrier is a LNP.

77. The protein-drug conjugate of claim 76, wherein the LNP further comprises apolynucleotide molecule and / or a polypeptide molecule.

78. The protein-drug conjugate of claim 76 or claim 77, wherein the LNP comprises one or more components of a gene editing system.

79. The protein-drug conjugate of claim 78, wherein the LNP comprises(a) a Cas nuclease, or a nucleic acid encoding the Cas nuclease, and / or(b) a guide RNA, or one or more DNAs encoding the guide RNA.

80. The protein-drug conjugate of claim 79, wherein the Cas nuclease is a Cas9 protein.

81. The protein-drug conjugate of claim 80, wherein the Cas9 protein is derived from a Streptococcus pyogenes Cas9 protein, a Staphylococcus aureus Cas9 protein, a Campylobacter jejuni Cas9 protein, a Streptococcus thermophilus Cas9 protein, ora Neisseria meningitidis Cas9 protein.

82. The protein-drug conjugate of any one of claims 79-81, wherein the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a mammalian cell.

83. The protein-drug conjugate of claim 82, wherein the nucleic acid encoding the Cas nuclease is codon-optimized for expression in a human cell.

84. The protein-drug conjugate of any one of claims 79-83, wherein the nucleic acid encoding the Cas nuclease is an mRNA.

85. The protein-drug conjugate of any one of claims 48, 56-59, and 79-84, wherein the guide RNA is a single guide RNA (sgRNA).

86. The protein-drug conjugate of claim 78, wherein the LNP comprises a zinc finger nuclease (ZFN), or a transcription activator-like effector nuclease (TALEN).

87. The protein-drug conjugate of any one of claims 76-86, wherein the LNP comprises a cationic lipid, a neutral lipid, a helper lipid, a stealth lipid, or any combination thereof.

88. The protein-drug conjugate of claim 87, wherein the neutral lipid is distearoylphosphatidylcholine (DSPC).

89. The protein-drug conjugate of claim 87, wherein the helper lipid is cholesterol.

90. The protein-drug conjugate of claim 87, wherein the stealth lipid is PEG2k-DMG.

91. A pharmaceutical composition comprising the antigen-binding protein of any one of claims 1 -38, the isolated polynucleotide of claim 39, the vector of claim 40, or theprotein-drug conjugate of any one of claims 43-90 and a pharmaceutically acceptable carrier.

92. A composition or kit comprising the antigen-binding protein of any one of claims 138, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 or pharmaceutical composition of claim 91 and a further therapeutic agent.

93. A complex comprising the antigen-binding protein of any one of claims 1 -38 or the protein-drug conjugate of any one of claims 43-90 bound to a human p75 neurotrophin receptor (p75NTR) polypeptide.

94. A method for making the antigen-binding protein of any one of claims 1-38, comprising culturing a host cell comprising a polynucleotide that encodes the antigen-binding protein in a culture medium under conditions favorable to expression of the antigen-binding protein.

95. The method of claim 94 comprising the steps:(a) introducing said polynucleotide into a host cell;(b) culturing the host cell under conditions favorable to expression of the antigenbinding protein;(c) optionally, isolating the antigen-binding protein from the culture medium and / or host cell; and(d) optionally, conjugating the antigen-binding protein to a molecular cargo.

96. An antigen-binding protein which is produced by or obtainable by the method of claim 94 or claim 95.

97. A method for making a protein-drug conjugate of any one of claims 43-90 comprising (a) contacting the antigen-binding protein, with the molecular cargo under the conditions favorable for conjugation of the antigen-binding protein to the molecular cargo; and(b) optionally, isolating the protein-drug conjugate produced in step (a).

98. A method for making a protein-drug conjugate of any one of claims 43-90, wherein the molecular cargo comprises a polypeptide molecule, comprising(a) culturing a host cell comprising a polynucleotide encoding the protein-drug conjugate under conditions that allow expression of the protein-drug conjugate; and (b) optionally, isolating the protein-drug conjugate produced in step (a).

99. A protein-drug conjugate which is produced by or obtainable by the method of claim 97 or claim 98.

100. A vessel or injection device comprising the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99.

101. A method for administering the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99 to a subject comprising introducing the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate into the body of the subject.

102. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration.

103. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

104. The method of claim 101, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

105. A method for delivering a molecular cargo to a tissue or cell type expressing p75NTR in the body of a subject comprising administering to the subject the protein-drug conjugate of any one of claims 43-90 and 99, or the pharmaceutical composition of claim 91.

106. The method of claim 105, wherein the tissue is brain, spinal cord, peripheral nervous system, autonomic nervous system, enteric nervous system, or eye.

107. The method of claim 106, wherein the tissue is brain or spinal cord.

108. The method of claim 105, wherein the cell type is a sensory neuron.

109. The method of claim 105, wherein the cell type is a dorsal root ganglion cell or atrigeminal ganglion cell.

110. The method of any one of claims 105-109, wherein the protein-drug conjugate is introduced into the body of the subject via subcutaneous, intramuscular, or intravenous administration.

111. The method of any one of claims 105-109, wherein the protein-drug conjugate is administered into the body of the subject via subcutaneous, intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

112. The method of any one of claims 105-109, wherein the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

113. The method of claim 107 or claim 110, wherein the protein-drug conjugate is administered into the body of the subject via subcutaneous administration.

114. The method of claim 107 or 111, wherein the protein-drug conjugate is administered into the body of the subject via intracerebroventricular administration.

115. A method for treating or preventing pain, itch, or a neurological disease or disorder in a subject in need thereof comprising administering to the subject an effective amount of the antigen-binding protein of any one of claims 1-38 and 96, the isolated polynucleotide of claim 39, the vector of claim 40, or the protein-drug conjugate of any one of claims 43-90 and 99, or the pharmaceutical composition of claim 91.

116. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered via subcutaneous, intramuscular, or intravenous administration.

117. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intrathecal, intracisternal, intracerebroventricular, or intraparenchymal administration.

118. The method of claim 115, wherein the antigen-binding protein, the polynucleotide, the vector, or the protein-drug conjugate is administered into the body of the subject via intravitreal administration into the eye.

119. The method of any one of claims 115-118, wherein the pain is peripheral chronic pain, a chronic neuropathic pain, somatic pain, chronic post-operative pain, small fiber peripheral neuropathy, chemotherapy-induced neuropathy, painful diabetic-induced neuropathy, post-herpetic neuralgia, osteoarthritis, back pain, joint pain, trigeminal neuralgia, trigeminal pain, temporo-mandibular pain, migraine, dysautonomia, or myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS).

120. The method of claim 119, wherein the chronic neuropathic pain is trigeminal pain or trigeminal neuralgia.

121. The method of any one of claims 115-118, wherein the itch is chronic itch.

122. The method of any one of claims 115-118, wherein the neurological disease ordisorder is a neurodegenerative disease, a neurodevelopmental disease, a chronicneuropathic pain, a physical injury, a neuropsychiatric disease, or a neurological cancer.

123. The method of claim 122, wherein the neurodegenerative disease or disorder is Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

124. The method of claim 122, wherein the physical injury is traumatic brain injury, spinal cord injury, stroke, or brain edema.

125. The method of claim 122, wherein the neurological cancer is a brain cancer or a peripheral nerve cancer.

126. The method of any one of claims 115-125, wherein the pain, itch, ora neurological disease or disorder is associated with a sensory neuron, a dorsal root ganglion cell, a trigeminal ganglion cell, or a population thereof.

127. The method of any one of claims 101-126, further comprising administering an additional treatment to the subject.

128. The method of claim 127, wherein the additional treatment comprises administering comprises administering a nonsteroidal anti-inflammatory drug (NSAID), acetaminophen, a local anesthetic, capsaicin, a Cox-2 inhibitor, an antidepressant, an anti-seizure medication, an anti-epileptic medication, an opioid, a steroid, an anticonvulsant, a muscle relaxant, a triptan, dihydroergotamine, Lasmiditan, a calcitonin gene-related peptides antagonist, an anti-nausea drug, a beta blocker, a calcium channel blocker, a serotonin and norepinephrine reuptake inhibitor (SNRI), onabotulinumtoxinA, or a benzodiazepine, or a combination thereof.

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