Anti-c2 antibodies and uses thereof

Abstract

The present disclosure relates to complement C2-binding proteins that specifically bind to an epitope within a serine protease domain of C2 and uses thereof.

Description

[0001] ANTI-C2 ANTIBODIES AND USES THEREOF

[0002] RELATED APPLICATION DATA

[0003] The present application claims priority from Australian Provisional Patent Application No. 2024901842 filed 17 June 2024 entitled “Anti-C2 antibodies and uses thereof’. The entire contents of this application are hereby incorporated by reference.

[0004] SEQUENCE LISTING

[0005] The present application is filed together with a Sequence Listing in electronic form. The entire contents of the Sequence Listing is hereby incorporated by reference.

[0006] FIELD

[0007] The present disclosure relates to complement C2-binding proteins that specifically bind to an epitope within a serine protease domain of C2 and uses thereof.

[0008] BACKGROUND

[0009] The complement system is a vital component of the humoral response against invading pathogens and includes pattern recognition molecules (PRMs), proenzymes, proteases, anaphylatoxins, opsonins, receptors, regulators and multi-molecular complexes that are critical to maintain normal tissue homeostasis. However, overactivation of complement is associated with pathology, e.g. in antibody-mediated transplant rejection, fibrosis and chronic autoimmune conditions. Complement C2, also known as complement component 2 is an early activator of the complement system. C2 (732 amino acids, -100 kDa) is produced in the liver as an inactive zymogen consisting of five domains: three N-terminal complement-control -proteins (CCP, amino acids 13- 223), a von Willebrand factor A-type (VW A) domain, and a C-terminal trypsin-like serine proteinase (SP) domain. C2 becomes rapidly activated by complement component C4b, which in itself is activated following antibody deposition (classical pathway) or carbohydrate recognition (lectin pathway) at the pathogen or cellular surface. The C4bC2 complex is cleaved by Cis or MASP2 into two fragments, C2a and C2b.

[0010] In order to clarify and standardize complement nomenclature, in 2019 the International Complement Society (ICS) and European Complement Network (ECN) proposed updates to the nomenclature of several names including cleavage products of C2. Based on the updated complement nomenclature, C2b is now used to refer to the larger, enzymatically active fragment, which is incorporated into the C3 convertase. The smaller fragment, now referred to as C2a is released into the fluid phase. Targeting C2 offers an opportunity to regulate the classical and lectin complement pathways without significantly impacting the alternative complement pathway. Thus, there is a need for agents that can inhibit C2 and / or reduce the amount of C2 in circulation in order to, for example, treat or prevent a complement-mediated disorder.

[0011] SUMMARY

[0012] The present inventors have produced a class of proteins comprising antigen binding sites (e.g., Fabs and antibodies) that binds to a serine protease domain of human complement C2. Accordingly, the present disclosure provides a C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain specifically binds to an epitope within a serine protease domain of C2. Variants of said C2-binding protein are derived from a common precursor and, while each variant is unique, they may retain a fundamental functional and structural relationship to each other and the original blueprint.

[0013] In one example, the C2-binding protein further binds to C2b. For example, the C2-binding protein binds to C2 and C2b, in particular is an anti-C2 antibody capable of binding to C2b.

[0014] In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 at neutral pH, and optionally acidic pH. For example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 at neutral and acidic pH.

[0015] In one example, the C2-binding protein binds C2 and inhibits C2 activity. For example, the C2-binding protein binds C2 and inhibits C2b catalytic activity. In one example, the C2-binding protein binds C2 and neutralizes C2b catalytic activity. For example, the C2-binding protein binds to C2 and C2b and inhibits C2b catalytic activity. In one example, the C2-binding protein binds to C2 and C2b and neutralizes C2b catalytic activity. In one example, the antigen binding domain binds to a region of C2 comprising amino acids 224-732 of SEQ ID NO: 1.

[0016] In one example, the C2-binding protein binds C2 at neutral pH, and optionally acidic pH, and inhibits C2 activity. For example, the C2-binding protein binds C2 at neutral and acidic pH and inhibits C2 activity. In one example, the C2-binding protein binds C2 at neutral and acidic pH and neutralizes C2b catalytic activity. In one example, the C2-binding protein binds C2 at neutral and acidic pH and neutralizes C2b catalytic activity at neutral and acidic pH.

[0017] In one example, the binding affinity of the target binding domain to the soluble molecule at acidic pH is substantially the same as binding at neutral pH or less than binding at neutral pH. In one example, the binding affinity of the target binding domain to the soluble molecule at acidic pH is about 10-, or about 9-, or about 8-, or about 7-, or about 6-, or about 5-, or about 4-, or about 3-, or about 2-fold less, or between 1-2 fold less than binding at neutral pH. In one example, the binding affinity of the target binding domain to the soluble molecule at acidic pH is substantially the same as binding at neutral pH.

[0018] In one example, the target binding domain does not necessarily have a faster dissociation rate from its soluble molecule at acidic pH compared to neutral pH.

[0019] In one example, the target binding domain optionally has a faster dissociation rate from its soluble molecule at acidic pH compared to neutral pH.

[0020] In one example, the C2 polypeptide comprises a sequence set forth in SEQ ID NO: 1. In one example, the C2 polypeptide consists of a sequence set forth in SEQ ID NO: 1.

[0021] In one example, the C2b polypeptide comprises a sequence set forth in SEQ ID NO: 481. In one example, the C2b polypeptide consists of a sequence set forth in SEQ ID NO: 481.

[0022] In one example, the C2-binding protein has a KD(PH6.0) / KD(PH7.4) value of less than 10, wherein the KD(PH6.0) / KD(PH7.4) value is defined as the ratio of the KD of the C2-binding protein for a C2 polypeptide at pH6.0 and the KD of the C2-binding protein for the C2 polypeptide at pH7.4, wherein the C2 polypeptide comprises a sequence set forth in SEQ ID NO: 1, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 7. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 5. For example, the Ko(pH6.0) / KD(pH7.4) for the C2 polypeptide is less than 3. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 2. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 1.9. For example, the KD(pH6.0) / Ko(pH7.4) for the C2 polypeptide is less than 1.8. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 1.6. For example, the KD(PH6.0) / KD(PH7.4) for the C2 polypeptide is less than 1.5.

[0023] In one example, the C2-binding protein has a Ko(C2) / KD(C2b) value of less than 20, wherein the Ko(C2) / KD(C2b) value is defined as the ratio of the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 and the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the Ko(C2) / KD(C2b) is less than 15. For example, the Ko(C2) / KD(C2b) is less than 10. For example, the Ko(C2) / KD(C2b) is less than 7. For example, the Ko(C2) / KD(C2b) is less than 5. For example, the Ko(C2) / KD(C2b) is less than 4.

[0024] C2-binding proteins of the present disclosure may be characterized based on binding properties and the dissociation constant KD. Accordingly, methods for determining the KD are described herein, wherein the C2-binding protein is immobilized on a solid biosensor surface (e.g. Sensor Chip CM5), contacted with the antigen and the KD is determined by a surface plasmon resonance assay at 37°C. In some examples, the KD is defined as being measurable via surface plasmon resonance assays at 37°C with a 10 mM HBS-EP+ buffer supplemented and 0.1% BSA.

[0025] In one example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity at or greater than a protein comprising an antigen binding domain comprising a heavy chain variable region (VH) of SEQ ID NO: 316 and a light chain variable region (VL) of SEQ ID NO: 222. For example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. In one example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity which is at least 1.2- fold greater, or at least 1.5-fold greater, or at least 2-fold greater or at least 10-fold greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. For example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity which is at least at least 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7- fold greater, at least 8-fold greater, at least 9-fold greater, at least 10-fold greater, at least 11-fold greater, or at least 12-fold greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. In one example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity which is at least 2-fold greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. In another example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity which is at least 5-fold greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. In another example, the C2-binding protein binds to C2 and C2b at pH7.4 with an affinity which is at least 10-fold greater than a protein comprising an antigen binding domain comprising a VH of SEQ ID NO: 316 and a VL of SEQ ID NO: 222. The respective dissociation constant KD is a measure of affinity with inverse relationship: a lower KD value indicates a higher affinity.

[0026] In one example, the C2-binding protein inhibits the classical complement pathway and / or the lectin complement pathway with an IC50 of 50 nM or less, or 25 nM or less, or 15 nM or less, or 10 nM or less, or 5 nM or less, or 1 nM or less, wherein the IC50 is determined by a complement assay and / or by a hemolytic assay. For example, the C2- binding protein inhibits the classical complement pathway with an IC50 of 50 nM or less, or 25 nM or less, or 15 nM or less, or 10 nM or less, or 5 nM or less, or 1 nM or less, wherein the IC50 is determined by a complement assay and / or by a hemolytic assay. In some examples, the IC50 is determined by a hemolytic assay. In some examples, the IC50 is determined by a complement assay. In one example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 50 nM or less. In another example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 25 nM or less. In a further example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 15 nM or less. In one example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 10 nM or less. In another example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 5 nM or less. In a further example, the C2-binding protein inhibits the classical complement pathway with an IC50 of 1 nM or less. In one example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 50 nM or less, or 25 nM or less, or 15 nM or less, or 10 nM or less, or 5 nM or less, or 1 nM or less, wherein the IC is determined by a complement assay and / or by a hemolytic assay. In one example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 50 nM or less. In another example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 25 nM or less. In a further example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 15 nM or less. In one example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 10 nM or less. In another example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 5 nM or less. In a further example, the C2-binding protein inhibits the lectin complement pathway with an IC50 of 1 nM or less.

[0027] Methods for determining the inhibitory activity of the C2-binding protein will be apparent to the skilled person and / or described herein. In one example, complement inhibitory activity is determined using an in vitro assay. For example, complement activity is measured using an enzyme immunoassay (e.g., an immunoassay that measures complement activation, such as a Wieslab® complement assay kit). For example, complement inhibitory activity is determined using labelled antibodies specific for an antigen or an epitope produced during complement activation (e.g., C5b-9 or an epitope present in C5b-C9). In one example, the wells of a microtitre plate are coated with specific activators of the classical, lectin or alternative pathway. In one example, the C2- binding protein of the disclosure is incubated with normal human serum and appropriate assay diluent (i.e., a diluent comprising appropriate blocking components to ensure specific activation of the classical, lectin or alternative pathway) and added to microtitre plate wells coated with specific activators of the classical, lectin or alternative pathway and the amount of C5b-9 complex formed is detected using a specific alkaline phosphatase labelled antibody to the C5b-9. In one example, the amount of complement activation product (i.e., C5b-9) produced is proportional to the functional activity of the complement pathway. In one example, the half-maximal inhibitor concentration (i.e., IC50) is determined. In another example, complement inhibitory activity is determined using a hemolysis assay (e.g., classical pathway (i.e., CH50) and alternative pathway (ApH50) inhibition assays).

[0028] In one example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 is less than 50 nM at pH 7.4, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 25 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 15 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 5 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 4 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2- binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 3 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 2 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 1.5 nM or less at pH 7.4. For example, the C2-binding protein has a KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 1 nM or less at pH 7.4.

[0029] In one example, (i) the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is about 10 nM or less, and (ii) the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is about 20 nM or less, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is about 10 nM or less, or about 9 nM or less, or about 8 nM or less, or about 7 nM or less, or about 6 nM or less, or about 5 nM or less, or about 4 nM or less, or about 3 nM or less, or about 2 nM or less, or about 1 nM or less, wherein KD is measurable using surface plasmon resonance assays at 37°C. In one example, the KD of the C2- binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is between about 2.5 nM and about 0.1 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is between about 1 nM and about 0.01 nM. For example, the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is about 1 nM, or about 0.9 nM, or about 0.8 nM, or about 0.7 nM, or about 0.6 nM, or about 0.5 nM, or about 0.4 nM, or about 0.3 nM, or about 0.2 nM, or about 0.1 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is about 0.1 nM, or about 0.09 nM, or about 0.08 nM, or about 0.07 nM, or about 0.06 nM, or about 0.05 nM, or about 0.04 nM, or about 0.03 nM, or about 0.02 nM, or about 0.01 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C. In one example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is about 20 nM or less, wherein KD is measurable using surface plasmon resonance assays at 37°C. In another example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is about 15 nM or less, or about 10 nM or less, or about 9 nM or less, or about 8 nM or less, or about 7 nM or less, or about 6 nM or less, or about 5 nM or less, or about 4 nM or less, or about 3 nM or less, or about 2 nM or less, or about 1 nM or less, wherein KD is measurable using surface plasmon resonance assays at 37°C. In one example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is between about 6.5 nM and about 0.1 nM, KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is between about 4 nM and about 0.1 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is between about 2 nM and about 0.1 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C. For example, the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is between about 1 nM and about 0.1 nM, wherein KD is measurable using surface plasmon resonance assays at 37°C.

[0030] In one example, the C2-binding protein has a KD for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 30 nM or less at pH 7.4, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C, for example C2-binding proteins having CDRs of antibodies from Table 5 with such an affinity to C2b. For example, in some embodiments the antigen binding domain comprises a combination of a VH and a VL or the antigen binding domain comprises the CDRs of said VH and VL, wherein the VH / VL combination has sequences with SEQ ID NOs selected from a group consisting of 316 / 222, 377 / 312, 364 / 222, 391 / 312, 361 / 312, 369 / 312, 376 / 312, 363 / 312, 376 / 284, 376 / 309, 376 / 315, 369 / 284, 369 / 309, 369 / 315,

[0031] 377 / 284, 377 / 309, 377 / 315, 361 / 284, 361 / 309, 361 / 315, 378 / 284, 378 / 309, 378 / 315,

[0032] 379 / 284, 379 / 309, 378 / 312, 379 / 315, 363 / 284, 363 / 309, 379 / 312, 363 / 315, 390 / 312,

[0033] 320 / 222, 329 / 222, 346 / 222, 347 / 222, 320 / 232, 347 / 232, 320 / 284, 320 / 309, 320 / 312,

[0034] 329 / 284, 329 / 309, 329 / 312, 329 / 232, 346 / 284, 346 / 309, 346 / 312, 346 / 232, 347 / 284,

[0035] 347 / 309, 347 / 312, 320 / 315, 347 / 315, 369 / 222, 373 / 222, 329 / 315, 346 / 315, 374 / 284,

[0036] 374 / 309, 359 / 312, 374 / 315, 375 / 284, 375 / 309, 375 / 315, 359 / 284, 359 / 309, 359 / 315,

[0037] 374 / 312, 375 / 312, 383 / 312, 386 / 312, 388 / 312, 316 / 284, 316 / 232, 316 / 309, 316 / 312,

[0038] 321 / 222, 323 / 222, 324 / 222, 328 / 222, 330 / 222, 331 / 222, 332 / 222, 333 / 222, 335 / 222,

[0039] 336 / 222, 337 / 222, 339 / 222, 341 / 222, 342 / 222, 343 / 222, 344 / 222, 345 / 222, 350 / 222,

[0040] 351 / 222, 352 / 222, 359 / 222, 360 / 222, 361 / 222, 362 / 222, 363 / 222, 316 / 235, 316 / 244,

[0041] 316 / 245, 316 / 246, 316 / 257, 316 / 260, 316 / 261, 316 / 267, 316 / 268, 316 / 277, 316 / 293,

[0042] 316 / 306, 316 / 307, 316 / 308, 316 / 310, 316 / 313, wherein the first number for each member of this group is the SEQ ID NO for VH and the second number is the SEQ ID NO for VL, in particular wherein the C2-binding protein is an anti-C2 antibody capable of binding to C2b.

[0043] In one example, the C2-binding protein has a KD at pH 7.4 for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 15 nM or less, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C, for example C2-binding proteins selected from Table 5 with such an affinity to C2b. For example, in some embodiments the antigen binding domain comprises a combination of a VH and a VL or the antigen binding domain comprises the CDRs of said VH and VL, wherein the VH / VL combination has sequences with SEQ ID NOs selected from a group consisting of 377 / 312, 391 / 312, 361 / 312, 369 / 312, 376 / 312, 363 / 312, 376 / 284, 376 / 309, 376 / 315, 369 / 284, 369 / 309, 369 / 315, 377 / 284, 377 / 309, 377 / 315, 361 / 284, 361 / 309, 361 / 315, 378 / 284, 378 / 309, 378 / 315, 379 / 284, 379 / 309, 378 / 312, 379 / 315, 363 / 284, 363 / 309, 379 / 312, 363 / 315, 320 / 222, 329 / 222, 346 / 222, 347 / 222, 320 / 232, 347 / 232, 320 / 284,

[0044] 320 / 309, 320 / 312, 329 / 284, 329 / 309, 329 / 312, 329 / 232, 346 / 284, 346 / 309, 346 / 312,

[0045] 346 / 232, 347 / 284, 347 / 309, 347 / 312, 320 / 315, 347 / 315, 369 / 222, 329 / 315, 346 / 315,

[0046] 374 / 284, 374 / 309, 359 / 312, 374 / 315, 375 / 284, 375 / 309, 375 / 315, 359 / 284, 359 / 309,

[0047] 359 / 315, 374 / 312, 375 / 312, 386 / 312, 388 / 312, 316 / 284, 316 / 309, 316 / 312, 321 / 222,

[0048] 328 / 222, 330 / 222, 332 / 222, 333 / 222, 335 / 222, 337 / 222, 339 / 222, 341 / 222, 342 / 222,

[0049] 343 / 222, 345 / 222, 350 / 222, 351 / 222, 352 / 222, 359 / 222, 360 / 222, 361 / 222, 362 / 222,

[0050] 363 / 222, 316 / 307, wherein the first number for each member of this group is the SEQ ID NO for VH and the second number is the SEQ ID NO for VL, in particular wherein the C2-binding protein is an anti-C2 antibody capable of binding to C2b.

[0051] In one example, the C2-binding protein has a KD at pH 7.4 for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 of about 6 nM or less, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C, for example C2-binding proteins selected from Table 5 with such an affinity to C2b. For example, in some embodiments the antigen binding domain comprises a combination of a VH and a VL or the antigen binding domain comprises the CDRs of said VH and VL, wherein the VH / VL combination has sequences with SEQ ID NOs selected from a group consisting of 377 / 312, 391 / 312, 361 / 312, 369 / 312, 376 / 312, 363 / 312, 376 / 284, 376 / 309, 376 / 315, 369 / 284, 369 / 309, 369 / 315, 377 / 284, 377 / 309, 377 / 315, 361 / 284, 361 / 309, 361 / 315,

[0052] 378 / 284, 378 / 309, 378 / 315, 379 / 284, 379 / 309, 378 / 312, 379 / 315, 363 / 284, 363 / 309,

[0053] 379 / 312, 363 / 315, 320 / 222, 329 / 222, 346 / 222, 347 / 222, 320 / 232, 347 / 232, 320 / 284,

[0054] 320 / 309, 320 / 312, 329 / 284, 329 / 309, 329 / 312, 329 / 232, 346 / 284, 346 / 309, 346 / 312,

[0055] 346 / 232, 347 / 284, 347 / 309, 347 / 312, 320 / 315, 347 / 315, 369 / 222, 329 / 315, 346 / 315,

[0056] 374 / 284, 374 / 309, 359 / 312, 374 / 315, 375 / 284, 375 / 309, 375 / 315, 359 / 284, 359 / 309,

[0057] 359 / 315, 374 / 312, 375 / 312, 316 / 309, 316 / 312, 321 / 222, 330 / 222, 339 / 222, 342 / 222,

[0058] 345 / 222, 350 / 222, 351 / 222, 352 / 222, 359 / 222, 360 / 222, 361 / 222, 362 / 222, 363 / 222, wherein the first number for each member of this group is the SEQ ID NO for VH and the second number is the SEQ ID NO for VL, in particular wherein the C2-binding protein is an anti-C2 antibody capable of binding to C2b.

[0059] In one example, the C2-binding protein has a KD at pH 7.4 for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 of about 1 nM or less, in particular wherein KD is measurable using surface plasmon resonance assays at 37°C, for example C2-binding proteins selected from Table 5 with such an affinity to C2. For example, in some embodiments the antigen binding domain comprises a combination of a VH and a VL or the antigen binding domain comprises the CDRs of said VH and VL, wherein the VH / VL combination has sequences with SEQ ID NOs selected from a group consisting of 377 / 312, 376 / 312, 369 / 312, 361 / 312, 376 / 284, 376 / 309, 376 / 315, 369 / 284, 369 / 309, 369 / 315, 377 / 284, 377 / 309, 377 / 315, 361 / 284, 361 / 309, 361 / 315, 378 / 284, 378 / 309,

[0060] 378 / 312, 378 / 315, 379 / 284, 379 / 309, 379 / 312, 379 / 315, 363 / 284, 363 / 309, 363 / 312,

[0061] 363 / 315, 383 / 312, 386 / 312, 320 / 222, 329 / 222, 346 / 222, 347 / 222, 320 / 232, 347 / 232,

[0062] 320 / 284, 320 / 309, 320 / 312, 329 / 284, 329 / 309, 329 / 312, 329 / 232, 346 / 284, 346 / 309,

[0063] 346 / 312, 346 / 232, 347 / 284, 347 / 309, 347 / 312, 320 / 315, 347 / 315, 369 / 222, 329 / 315,

[0064] 346 / 315, 374 / 284, 374 / 309, 374 / 312, 374 / 315, 375 / 284, 375 / 309, 375 / 312, 375 / 315,

[0065] 359 / 284, 359 / 309, 359 / 312, 359 / 315, 330 / 222, 339 / 222, 342 / 222, 345 / 222, 350 / 222,

[0066] 351 / 222, 352 / 222, 359 / 222, 361 / 222, 362 / 222, 363 / 222, wherein the first number for each member of this group is the SEQ ID NO for VH and the second number is the SEQ ID NO for VL, in particular wherein the C2-binding protein is an anti-C2 antibody capable of binding to C2.

[0067] In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising one or more or all amino acids corresponding to residues 538, 541, 625, 628, 656, 681, 686, 695 of SEQ ID NO: 1. In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising one or more or all amino acids corresponding to residues 538, 625, 628, 656, 681, 686, 695 of SEQ ID NO: l.In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 538 of SEQ ID NO: 1. In another example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 541 of SEQ ID NO: 1. In a further example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 625 of SEQ ID NO: 1. In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 628 of SEQ ID NO: 1. In another example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 656 of SEQ ID NO: 1. In a further example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 681 of SEQ ID NO: 1. In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 686 of SEQ ID NO: 1. In another example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising residue 695 of SEQ ID NO: 1. In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising one or more or all amino acids corresponding to residues 538, 625, 628, 656, 681, 686, 695 of SEQ ID NO: 1. In another example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising all amino acids corresponding to residues 538, 625, 628, 656, 681, 686, 695 of SEQ ID NO: 1.

[0068] In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising at least one, or at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8 of the amino acids at residues 538, 541, 625, 628, 656, 681, 686, 695 of SEQ ID NO: 1. In one example, the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising at least one, or at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8 of the amino acids at residues 538, 625, 628, 656, 681, 686, 695of SEQ ID NO: 1.

[0069] In one example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for one of:

[0070] (i) lysine at position 656 of SEQ ID NO: 1;

[0071] (ii) lysine at position 695 of SEQ ID NO: 1;

[0072] (iii) leucine at position 681 of SEQ ID NO: 1;

[0073] (iv) leucine at position 686 of SEQ ID NO: 1;

[0074] (v) tyrosine at position 538 of SEQ ID NO: 1;

[0075] (vi) methionine at position 628 of SEQ ID NO: 1; or

[0076] (vii) glutamic acid at position 625 of SEQ ID NO: 1, is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1.

[0077] In one example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for lysine at position 656 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In another example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for lysine at position 695 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In a further example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for leucine at position 681 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In one example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for leucine at position 686 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In another example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for tyrosine at position 538 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In a further example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for methionine at position 628 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1. In one example, the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for glutamic acid at position 625 of SEQ ID NO: 1 is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1.

[0078] In one example, the affinity of the C2-binding protein to:

[0079] (i) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for lysine at position 656;

[0080] (ii) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for lysine at position 695;

[0081] (iii) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for leucine at position 681;

[0082] (iv) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for leucine at position 686;

[0083] (v) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for tyrosine at position 538;

[0084] (vi) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for methionine at position 628; or

[0085] (vii) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for glutamic acid at position 625, is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1.

[0086] In some examples, the affinity of the C2-binding protein for the polypeptide comprising the substitution is at least 5-fold, 10-fold, 15-fold, or 20-fold lower than the affinity of the C2-binding protein to the polypeptide of SEQ ID NO: 1. In some examples, the affinity of the C2-binding protein for the polypeptide comprising the substitution is at least 10-fold lower than the affinity of the C2-binding protein to the polypeptide of SEQ ID NO: 1. In some examples, the affinity of the C2-binding protein for the polypeptide comprising the substitution is at least 20-fold lower than the affinity of the C2-binding protein to the polypeptide of SEQ ID NO: 1.

[0087] In one example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 681 and / or 695 and / or 538 of SEQ ID NO: 1. For example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 681 of SEQ ID NO: 1. In another example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 695 of SEQ ID NO: 1. In one example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 538 of SEQ ID NO: 1. In a further example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 681 and 695 of SEQ ID NO: 1. In another example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 538 and 681 of SEQ ID NO: 1. In another example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 538 and 695 of SEQ ID NO: 1. In one example, the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 538, 681 and 695 of SEQ ID NO: 1.

[0088] In one example, the C2-binding protein does not detectably bind:

[0089] (i) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for a lysine at position 695; and / or

[0090] (ii) a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for a leucine at position 681; and / or

[0091] (iii)a polypeptide of SEQ ID NO: 1 in which an alanine is substituted for a tyrosine at position 538.

[0092] Additional forms of a polypeptide comprising the amino acids of SEQ ID NO: 1 with or without other substitutions bound or not significantly bound or not detectably bound by a C2-binding protein of the present disclosure are described herein and are to be taken to apply mutatis mutandis to the present examples of the disclosure.

[0093] In one example, the antigen binding domain comprises a VH comprising complementarity determining regions (CDRs) 1, 2 and 3 of a VH sequence set forth in SEQ ID NO: 393 or 395; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in SEQ ID NO: 392 or 394; or the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NO: 222 to 315.

[0094] In one example, the antigen binding domain comprises:

[0095] (i) a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 214; a CDR2 comprising a sequence set forth in SEQ ID NO: 215; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 217; a CDR2 comprising a sequence set forth in SEQ ID NO: 218; and a CDR3 comprising a sequence set forth in SEQ ID NO: 219, or

[0096] (ii) a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 214; a CDR2 comprising a sequence set forth in SEQ ID NO: 215; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 217; and a CDR2 comprising a sequence set forth in SEQ ID NO: 220; and a CDR3 comprising a sequence set forth in SEQ ID NO: 221, wherein the CDRs are defined according to the numbering system of KABAT.

[0097] In one example of any disclosure herein, the CDRs are defined according to the numbering system of KABAT wherein the VH comprises a CDR1 comprising amino acid residues 31 to 35 of any VH sequence described herein; a CDR2 comprising amino acid residues 50 to 66 of any VH sequence described herein; and a CDR3 comprising amino acid residues 99 to 114 of any VH sequence described herein; and the VL comprises a CDR1 comprising amino acid residues 24 to 35 of any VL sequence described herein; a CDR2 comprising amino acid residues 51 to 57 of any VL sequence described herein; and a CDR3 comprising amino acid residues 90 to 100 of any VL sequence described herein.

[0098] In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 393 or 395; and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 392 or 394.

[0099] In one example, the antigen binding domain comprises a VH comprising CDRs 1,

[0100] 2 and 3 of a sequence set forth in SEQ ID NO: 393; and a VL comprising CDRs 1, 2 and

[0101] 3 of a sequence set forth in SEQ ID NO: 392.

[0102] In one example, the antigen binding domain comprises a VH comprising a sequence set forth in SEQ ID NO: 393, wherein the amino acid sequence comprises Alanine (A) or Serine (S) at position 9 and / or Aspartic Acid (D) or Glutamic Acid (E) or Histidine (H) or Isoleucine (I) or Glutamine (Q) or Serine (S) or Tyrosine (Y) at position 28 and / or Aspartic Acid (D) or Leucine (L) or Asparagine (N) or Threonine (T) or Tyrosine (Y) at position 30 and / or Alanine (A) or Histidine (H) or Leucine (L) or Serine (S) or Tyrosine (Y) at position 31 and / or Tryptophan (W) or Tyrosine (Y) at position 33 and / or Glycine (G) or Leucine (L) at position 44 and / or Leucine (L) or Tyrosine (Y) at position 52 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) at position 54 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 55 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 57 and / or Lysine (K) or Leucine (L) or Glutamine (Q) or Arginine (R) or Tyrosine (Y) at position 59 and / or Lysine (K) or Glutamine (Q) at position 67 and / or Alanine (A) or Threonine (T) at position 72 and / or Alanine (A) or Threonine (T) at position 79 and / or Leucine (L) or Tryptophan (W) at position 83 and / or Lysine (K) or Arginine (R) at position 98 and / or Lysine (K) or Arginine (R) or Serine (S) at position 99 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) or Serine (S) at position 100 and / or Glycine (G) or Leucine (L) or Serine (S) at position 101 and / or Glycine (G) or Leucine (L) or Serine (S) or Tyrosine (Y) at position 102 and / or Phenylalanine (F) or Leucine (L) or Tryptophan (W) at position 105 and / or Alanine (A) or Glycine (G) or Serine (S) at position 106 and / or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 109.

[0103] In one example, the antigen binding domain comprises a VL comprising a sequence set forth in SEQ ID NO: 392, wherein the amino acid sequence comprises Arginine (R) or Serine (S) at position 11 and / or Glutamic Acid (E) or Lysine (K) or Glutamine (Q) or Arginine (R) or Serine (S) or Tyrosine (Y) at position 26 and / or Alanine (A) or Aspartic Acid (D) or Glycine (G) or Glutamine (Q) or Tyrosine (Y) at position 30 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Lysine (K) or Leucine (L) or Asparagine (N) or Serine (S) or Valine (V) or Tyrosine (Y) at position 31 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Asparagine (N) or Serine (S) or Tyrosine (Y) at position 32 and / or Aspartic Acid (D) or Glutamic Acid (E) or Asparagine (N) or Glutamine (Q) or Tyrosine (Y) at position 33 and / or Aspartic Acid (D) or Glutamic Acid (E) or Serine (S) at position 51 and / or Alanine (A) or Aspartic Acid (D) or Glutamic Acid (E) or Histidine (H) or Lysine (K) or Asparagine (N) or Serine (S) at position 53 and / or Lysine (K) or Asparagine (N) or Arginine (R) or Serine (S) or Threonine (T) at position 54 and / or Proline (P) or Glutamine (Q) at position 60 and / or Isoleucine (I) or Serine (S) at position 71 and / or Alanine (A) or Serine (S) at position 75 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 92 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Lysine (K) or Leucine (L) or Asparagine (N) or Proline (P) or Serine (S) or Tyrosine (Y) at position 94 and / or Alanine (A) or Lysine (K) or Arginine (R) at position 97 and / or Lysine (K) or Leucine (L) or Arginine (R) at position 99.

[0104] In one example, the antigen binding domain comprises a VH comprising CDRs 1,

[0105] 2 and 3 of a sequence set forth in SEQ ID NO: 395; and a VL comprising CDRs 1, 2 and

[0106] 3 of a sequence set forth in SEQ ID NO: 394.

[0107] In one example, the antigen binding domain comprises a VH comprising a sequence set forth in SEQ ID NO: 395, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) or Histidine (H) or Isoleucine (I) or Serine (S) or Tyrosine (Y) at position 28 and / or Aspartic Acid (D) or Leucine (L) or Asparagine (N) or Threonine (T) or Tyrosine (Y) at position 30 and / or Alanine (A) or Leucine (L) or Serine (S) at position 31 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) at position 54 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 57 and / or Lysine (K) or Leucine (L) or Glutamine (Q) or Arginine (R) or Tyrosine (Y) at position 59 and / or Lysine (K) or Arginine (R) at position 98 and / or Lysine (K) or Arginine (R) at position 99 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) or Serine (S) at position 100 and / or Leucine (L) or Tyrosine (Y) at position 102 and / or Phenylalanine (F) or Tryptophan (W) at position 105 and / or Alanine (A) or Glycine (G) or Serine (S) at position 106 and / or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 109.

[0108] In one example, the antigen binding domain comprises a VL comprising a sequence set forth in SEQ ID NO: 394, wherein the amino acid sequence comprises Lysine (K) or Glutamine (Q) or Arginine (R) or Serine (S) at position 26 and / or Alanine (A) or Aspartic Acid (D) or Glycine (G) or Glutamine (Q) or Tyrosine (Y) at position 30 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Lysine (K) or Leucine (L) or Asparagine (N) or Serine (S) or Valine (V) or Tyrosine (Y) at position 31 and / or Aspartic Acid (D) or Histidine (H) or Asparagine (N) or Serine (S) at position 32 and / or Aspartic Acid (D) or Glutamic Acid (E) or Tyrosine (Y) at position 33 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 51 and / or Aspartic Acid (D) or Histidine (H) or Asparagine (N) or Serine (S) at position 53 and / or Lysine (K) or Arginine (R) at position 54 and / or Tryptophan (W) or Tyrosine (Y) at position 92 and / or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Serine (S) or Tyrosine (Y) at position 94 and / or Alanine (A) or Lysine (K) or Arginine (R) at position 97, and / or Lysine (K) or Leucine (L) or Arginine (R) at position 99.

[0109] In one example, the antigen binding domain comprises a VH comprising CDRs 1,

[0110] 2 and 3 of a sequence set forth in SEQ ID NO: 533; and a VL comprising CDRs 1, 2 and

[0111] 3 of a sequence set forth in SEQ ID NO: 531. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 534; and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 531. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 377; and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 531. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 533 and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 532. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 534; and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 532. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 377; and a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 532.

[0112] In one example, the antigen binding domain comprises a VH comprising a sequence set forth in SEQ ID NO: 533, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 54 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 55 and / or Serine (S) or Leucine (L) at position 56 and / or Leucine (L) or Threonine (T) at position 57 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 58 and / or Arginine (R) or Lysine (K) at position 98 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 110 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 113.

[0113] In one example, the antigen binding domain comprises a VH comprising a sequence set forth in SEQ ID NO: 534, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 54 and / or Serine (S) or Leucine (L) at position 56 and / or Leucine (L) or Threonine (T) at position 57 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 58.

[0114] In one example, the antigen binding domain comprises a VL comprising a sequence set forth in SEQ ID NO: 531, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 31 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 52 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 53 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 93.

[0115] In one example, the antigen binding domain comprises a VL comprising a sequence set forth in SEQ ID NO: 532, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 31 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 53 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 93.

[0116] In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NO: 222 to 315, wherein the CDRs are defined according to the numbering system of KABAT. For example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 222 to 315, wherein the CDRs are defined according to the numbering system of KABAT. It will be apparent to the skilled person from the foregoing that the three CDRs are from the same VH sequence and / or the three CDRs are from the same VL sequence. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NOs: 377, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NOs: 312, 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT. For example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 377, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 312, 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT. It will be apparent to the skilled person from the foregoing that the three CDRs are from the same VH sequence and / or the three CDRs are from the same VL sequence.

[0117] In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NOs: 316 to 391, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NO : 222 to 315 or 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT. For example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 316 to 391, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of one sequence of any one of SEQ ID NO: 222 to 315 or 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT. It will be apparent to the skilled person from the foregoing that the three CDRs are from the same VH sequence and / or the three CDRs are from the same VL sequence.

[0118] In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 316. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 317. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 318. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 319. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 320. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 321. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 322. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 323. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 324. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 325. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 326. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 328. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 329. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 330. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 331. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 332. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 333. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 334. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 335. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 336. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 337. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 338. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 339. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 340. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 341. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 342. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 343. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 344. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 345. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 346. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 347. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 349. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 350. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 351. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 352. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 353. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 354. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 355. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 356. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 357. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 358. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 359. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 360. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 361. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 362. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 363. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 364. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 368. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 369. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 370. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 372. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 373. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 374. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 375. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 376. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 377. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 378. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 379. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 380. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 382. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 383. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 384. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 385. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 386. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 387. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 388. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 389. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 390. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 391. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 520. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 521. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 522. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 523. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 524. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 525. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 526. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 527. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 528. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 529. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 530. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 546. In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 547. The above CDRs are defined according to the numbering system of KABAT.

[0119] In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 222. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 223. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 224. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 225. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 226. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 227. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 228. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 229. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 230. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 231. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 232. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 233. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 234. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 235. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 236. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 237. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 238. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 239. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 240. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 241. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 242. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 243. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 244. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 245. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 246. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 247. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 248. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 249. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 250. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 251. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 252. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 253. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 254. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 255. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 256. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 257. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 258. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 259. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 260. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 261. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 262. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 263. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 264. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 265. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 266. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 267. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 268. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 269. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 270. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 271. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 272. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 273. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 274. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 275. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 276. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 277. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 278. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 279. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 280. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 281. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 282. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 283. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 284. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 285. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 286. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 287. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 288. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 289. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 290. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 291. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 292. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 293. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 294. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 295. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 296. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 297. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 298. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 299. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 300. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 301. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 302. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 303. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 304. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 305. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 306. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 307. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 308. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 309. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 310. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 311. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 312. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 313. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 314. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 315. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 515. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 516. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 517. In one example, the antigen binding domain comprises a VL comprising CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 518. In one example, the antigen binding domain comprises a VL comprising CDRs

[0120] I, 2 and 3 of a sequence set forth in SEQ ID NO: 519. The above CDRs are defined according to the numbering system of KABAT.

[0121] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 214; and a CDR2 comprising a sequence set forth in SEQ ID NO: 215; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 217; and a CDR2 comprising a sequence set forth in SEQ ID NO: 218; and a CDR3 comprising a sequence set forth in SEQ ID NO: 219, wherein the CDRs are defined according to the numbering system of KABAT.

[0122] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 214, wherein the amino acid sequence comprises Glutamic Acid (E) or Lysine (K) or Glutamine (Q) or Arginine (R) or Serine (S) or Tyrosine (Y) at position 4 and / or Alanine (A) or Aspartic Acid (D) or Glycine (G) or Glutamine (Q) or Tyrosine (Y) at position 8 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Lysine (K) or Leucine (L) or Asparagine (N) or Serine (S) or Valine (V) or Tyrosine (Y) at position 9 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Asparagine (N) or Serine (S) or Tyrosine (Y) at position 10 and / or Aspartic Acid (D) or Glutamic Acid (E) or Asparagine (N) or Glutamine (Q) or Tyrosine (Y) at position

[0123] I I.

[0124] In one example, the antigen binding domain comprises a VL comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 215, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) or Serine (S) at position 1 and / or Alanine (A) or Aspartic Acid (D) or Glutamic Acid (E) or Histidine (H) or Lysine (K) or Asparagine (N) or Serine (S) ) at position 3 and / or Lysine (K) or Asparagine (N) or Arginine (R) or Serine (S) or Threonine (T) at position 4.

[0125] In one example, the antigen binding domain comprises a VL comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 216, wherein the amino acid sequence comprises Alanine (A) or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 3 and / or Alanine (A) or Aspartic Acid (D) or Histidine (H) or Lysine (K) or Leucine (L) or Asparagine (N) or Proline (P) or Serine (S) or Tyrosine (Y) at position 5 and / or Alanine (A) or Lysine (K) or Arginine (R) at position 8 and / or Lysine (K) or Leucine (L) or Arginine (R) at position 10.

[0126] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 217, wherein the amino acid sequence comprises Alanine (A), or Histidine (H) or Leucine (L) or Serine (S) or Tyrosine (Y) at position 1.

[0127] In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 218, wherein the amino acid sequence comprises Leucine (L) or Tyrosine (Y) at position 3 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) at position 5 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 6 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 8 and / or Lysine (K) or Leucine (L) or Glutamine (Q) or Arginine (R) or Tyrosine (Y) at position 10.

[0128] In one example, the antigen binding domain comprises a VH comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 219, wherein the amino acid sequence comprises Lysine (K) or Arginine (R) or Serine (S) at position 1 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) or Serine (S) at position 2 and / or Glycine (G) or Leucine (L) or Serine (S) at position 3 and / or Glycine (G) or Leucine (L) or Serine (S) or Tyrosine (Y) at position 4 and / or Phenylalanine (F) or Leucine (L) or Tryptophan (W) at position 7 and / or Alanine (A) or Glycine (G) or Serine (S) at position 8 and / or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 11.

[0129] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 214; and a CDR2 comprising a sequence set forth in SEQ ID NO: 215; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 217; and a CDR2 comprising a sequence set forth in SEQ ID NO: 220; and a CDR3 comprising a sequence set forth in SEQ ID NO: 221, wherein the CDRs are defined according to the numbering system of KABAT.

[0130] In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 220, wherein the amino acid sequence comprises Lysine (K) or Arginine (R) at position 10. In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 220, wherein the amino acid sequence comprises Lysine (K) at position 10. In another example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 220, wherein the amino acid sequence comprises Arginine (R) at position 10.

[0131] In one example, the antigen binding domain comprises a VH comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 221, wherein the amino acid sequence comprises Glycine (G) or Serine (S) at position 2 and / or Phenylalanine (F) or Tryptophan (W) at position 7 and / or Alanine (A) or Glycine (G) at position 8 and / or Glutamine (Q) or Tyrosine (Y) at position 11.

[0132] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 535; and a CDR2 comprising a sequence set forth in SEQ ID NO: 536; and a CDR3 comprising a sequence set forth in SEQ ID NO: 538; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; and a CDR2 comprising a sequence set forth in SEQ ID NO: 539; and a CDR3 comprising a sequence set forth in SEQ ID NO: 541, wherein the CDRs are defined according to the numbering system of KABAT.

[0133] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 535, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 9.

[0134] In one example, the antigen binding domain comprises a VL comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 536, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 2 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 3.

[0135] In one example, the antigen binding domain comprises a VL comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 538, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 4.

[0136] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161.

[0137] In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 539, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 5 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 6 and / or Leucine (L) or Serine (S) at position 7 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 8 and / or Threonine (T) or Leucine (L) at position 9.

[0138] In one example, the antigen binding domain comprises a VH comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 541, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 12 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 15. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 535; and a CDR2 comprising a sequence set forth in SEQ ID NO: 537; and a CDR3 comprising a sequence set forth in SEQ ID NO: 538; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; and a CDR2 comprising a sequence set forth in SEQ ID NO: 540; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198, wherein the CDRs are defined according to the numbering system of KABAT.

[0139] In one example, the antigen binding domain comprises a VL comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 537, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 3.

[0140] In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 540, wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 5 and / or Leucine (L) or Serine (S) at position 7 and / or Aspartic Acid (D) or Glutamic Acid (E) at position 8 and / or Threonine (T) or Leucine (L) at position 9.

[0141] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 535; and a CDR2 comprising a sequence set forth in SEQ ID NO: 537; and a CDR3 comprising a sequence set forth in SEQ ID NO: 538; and a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; and a CDR2 comprising a sequence set forth in SEQ ID NO: 171; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198, wherein the CDRs are defined according to the numbering system of KABAT.

[0142] Whilst the above CDRs have been defined according to KABAT, the skilled person would be able to readily identify the corresponding CDRs according to IMGT.

[0143] In one example, the antigen binding domain comprises:

[0144] (i) a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159 to 164; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2 to 82; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83 to 106; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107 to 158, or

[0145] (ii) a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159, 161, or 164; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 168, 170 to 174, or 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 179, 181, 184 to 186, 188 to 191, 193, 198, 202 to 204, or 210 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2, 8, 11, 20 to 22, 33, 36, 37, 41, 42, 50, 57, or 76 to 82; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83, 84, 86, 87, 92, 94 or 102; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107, 108, 111, 113, 115, 117 to 119, 126, 128, 132, 133, 136, 140, 147, 156, or 158, wherein the CDRs are defined according to the numbering system of KABAT.

[0146] In one example, the antigen binding domain comprises:

[0147] (i) a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159 to 164; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2 to 82; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83 to 106; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107 to 158, or

[0148] (ii) a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159, 161, or 164; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 168, 170 to 174, or 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 179, 181, 184 to 186, 188 to 191, 193, 198, 202 to 204, or 210 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2, 8, 11, 20 to 22, 33, 36, 37, 41, 42, 50, 57, or 76 to 82; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83, 84, 86, 87, 92, 94 or 102; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107, 108, 111, 113, 115, 117 to 119, 126, 128, 132, 133, 136, 140, 147, 156, or 158, or

[0149] (iii) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 171, 502 to 512; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 198, 513 or 514; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84, 499 or 500; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501,

[0150] (iv) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 171, 502 to 506; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84 or 499; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501,

[0151] (v) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in SEQ ID NO: 171; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84 or 499; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501, wherein the CDRs are defined according to the numbering system of KABAT.

[0152] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159 to 164; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2 to 82; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83 to 106; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107 to 158.

[0153] In one example, the VH comprises a CDR1, CDR2 and CDR3 from one sequence of any one of the sequences of the disclosure, wherein the CDRs are defined according to the numbering system of KABAT. In another example, the VL comprises a CDR1, CDR2 and CDR3 from one sequence of any one of the sequences of the disclosure, wherein the CDRs are defined according to the numbering system of KABAT.

[0154] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 159, 161, or 164; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 165 to 168, 170 to 174, or 176; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 177 to 179, 181, 184 to 186, 188 to 191, 193, 198, 202 to 204, or 210 to 213; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 2, 8, 11, 20 to 22, 33, 36, 37, 41, 42, 50, 57, or 76 to 82; and a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 83, 84, 86, 87, 92, 94 or 102; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107, 108, 111, 113, 115, 117 to 119, 126, 128, 132, 133, 136, 140, 147, 156, or 158, wherein the CDRs are defined according to the numbering system of KABAT.

[0155] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 171, 502 to 512; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 198, 513 or 514; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84, 499 or 500; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501, wherein the CDRs are defined according to the numbering system of KABAT.

[0156] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 171, 502 to 506; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84 or 499; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501, wherein the CDRs are defined according to the numbering system of KABAT.

[0157] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; a CDR2 comprising a sequence set forth in SEQ ID NO: 171; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NOs: 81 or 498; a CDR comprising a sequence set forth in any one of SEQ ID NOs: 84 or 499; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158 or 501, wherein the CDRs are defined according to the numbering system of KABAT.

[0158] In one example, the antigen binding domain comprises a VH comprising:

[0159] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; or

[0160] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; or

[0161] (iii) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; or

[0162] (iv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0163] (v) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; or (vi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198.

[0164] In one example, the antigen binding domain comprises a VH comprising:

[0165] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; or

[0166] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; or

[0167] (iii) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; or

[0168] (iv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0169] (v) a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; or

[0170] (vi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0171] (vii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 502 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0172] (viii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 503 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0173] (ix) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 504 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0174] (x) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 505 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or (xi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 506 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0175] (xii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 507 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0176] (xiii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 508 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0177] (xiv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 509 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0178] (xv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 510 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0179] (xvi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 511 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0180] (xvii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 512 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198;

[0181] (xviii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 513; or

[0182] (xix) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 514.

[0183] In one example, the antigen binding domain comprises a VH comprising:

[0184] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0185] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 502 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or (iii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 503 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0186] (iv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 504 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0187] (v) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 505 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0188] (vi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 506 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0189] (vii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 507 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0190] (viii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 508 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0191] (vix) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 509 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0192] (x) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 510 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0193] (xi) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 511 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; or

[0194] (xii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 512 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198;

[0195] (xiii) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 513; or

[0196] (xiv) a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 514. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0197] 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 160, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0198] 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0199] 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 167 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0200] 179. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0201] 180. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0202] 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0203] 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0204] 182. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 170 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0205] 185. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 172 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0206] 186. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 173 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0207] 187. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0208] 188. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 187. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 173 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0209] 190. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 180. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0210] 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 163, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0211] 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 174 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0212] 191. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 179. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 164, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0213] 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 170 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 191. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0214] 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0215] 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0216] 178. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0217] 197. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0218] 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0219] 199. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0220] 202. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0221] 203. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0222] 203. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0223] 204. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0224] 205. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 207. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0225] 208. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0226] 209. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0227] 210. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0228] 211. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0229] 212. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0230] 213. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 502 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 503 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 504 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 505 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 506 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 507 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 508 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 509 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 510 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 511 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 512 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0231] 513. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0232] 514.

[0233] In one example, the antigen binding domain comprises a VL comprising:

[0234] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107; or

[0235] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158.

[0236] In one example, the antigen binding domain comprises a VL comprising:

[0237] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107; or

[0238] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; and a heavy chain variable region (VH) comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391, wherein the CDRs are defined according to the numbering system of KABAT.

[0239] In one example, the antigen binding domain comprises a VL comprising:

[0240] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107; or

[0241] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0242] (iii) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0243] (iv) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0244] (v) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0245] (vi) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501; or

[0246] (vii) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 500 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158.

[0247] In one example, the antigen binding domain comprises a VL comprising:

[0248] (i) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0249] (ii) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0250] (iii) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or (iv) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; or

[0251] (v) a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501; or

[0252] (vi) a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 500 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158.

[0253] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 3, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 4, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 5, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 85 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 6, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 3, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 7, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0254] 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 9, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0255] 109. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 10, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0256] 110. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 11, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0257] 111. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 12, a CDR2 comprising a sequence set forth in SEQ ID NO: 88 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0258] 112. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 13, a CDR2 comprising a sequence set forth in SEQ ID NO: 89 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0259] 113. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 14, a CDR2 comprising a sequence set forth in SEQ ID NO: 90 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0260] 114. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 15, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0261] 115. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 16, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0262] 116. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 17, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 18, a CDR2 comprising a sequence set forth in SEQ ID NO: 91 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0263] 117. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 19, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 118. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 20, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0264] 119. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 21, a CDR2 comprising a sequence set forth in SEQ ID NO: 92 and a CDR3 comprising a sequence set forth in SEQ ID NO: 118. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 22, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 115. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 23, a CDR2 comprising a sequence set forth in SEQ ID NO: 93 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0265] 120. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 24, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0266] 121. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 25, a CDR2 comprising a sequence set forth in SEQ ID NO: 95 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0267] 122. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 26, a CDR2 comprising a sequence set forth in SEQ ID NO: 96 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0268] 123. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 27, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 28, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0269] 124. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 29, a CDR2 comprising a sequence set forth in SEQ ID NO: 97 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 30, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 99 and a CDR3 comprising a sequence set forth in SEQ ID NO: 114. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 32, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0270] 125. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 33, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0271] 126. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 34, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0272] 127. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 35, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0273] 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 36, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0274] 128. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 37, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0275] 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 16, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0276] 129. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0277] 130. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 38, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 125. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 39, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0278] 131. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 40, a CDR2 comprising a sequence set forth in SEQ ID NO: 100 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 41, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 132. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 42, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0279] 133. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 25, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0280] 134. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 43, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0281] 125. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 44, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 130. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 45, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 46, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 117. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 47, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 130. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 48, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0282] 126. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 49, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0283] 135. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 50, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0284] 136. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 51, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0285] 137. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 52, a CDR2 comprising a sequence set forth in SEQ ID NO: 101 and a CDR3 comprising a sequence set forth in SEQ ID NO: 138. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 53, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0286] 139. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 54, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0287] 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 55, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0288] 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 56, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0289] 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0290] 140. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 58, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0291] 141. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 59, a CDR2 comprising a sequence set forth in SEQ ID NO: 103 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0292] 142. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 60, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0293] 143. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 61, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0294] 144. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 62, a CDR2 comprising a sequence set forth in SEQ ID NO: 104 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0295] 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 63, a CDR2 comprising a sequence set forth in SEQ ID NO: 105 and a CDR3 comprising a sequence set forth in SEQ ID NO: 145. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 64, a CDR2 comprising a sequence set forth in SEQ ID NO: 91 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0296] 146. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 20, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0297] 147. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 65, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0298] 148. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 66, a CDR2 comprising a sequence set forth in SEQ ID NO: 106 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0299] 125. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 67, a CDR2 comprising a sequence set forth in SEQ ID NO: 90 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0300] 126. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 68, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0301] 149. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 69, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0302] 150. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 70, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0303] 151. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 71, a CDR2 comprising a sequence set forth in SEQ ID NO: 95 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 50, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0304] 152. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 72, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 73, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 153. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 74, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0305] 154. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 75, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0306] 155. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 76, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 117. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 77, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0307] 156. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 78, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 113. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 80, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 61, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0308] 157. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0309] 158. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 82, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 156. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 92 and a CDR3 comprising a sequence set forth in SEQ ID NO: 115. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 500 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158.

[0310] In one example the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 312 and the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391, wherein the CDRs are defined according to the numbering system of KABAT; and / or the VL comprises a sequence set forth in SEQ ID NO: 312 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391.

[0311] In one example, the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 222 and VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389, wherein the CDRs are defined according to the numbering system of KABAT; and / or the VL comprises a sequence set forth in SEQ ID NO: 222 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389.

[0312] The present disclosure provides a C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises:

[0313] (i) a VH comprising CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 222 to 315, wherein the CDRs are defined according to the numbering system of KABAT; and / or

[0314] (ii) a VH comprising a sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising a sequence set forth in any one of SEQ ID NO: 222 to 315.

[0315] The present disclosure provides a C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises:

[0316] (i) a VH comprising CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316 to 391, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 222 to 315 or 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT; and / or

[0317] (ii) a VH comprising a sequence set forth in any one of SEQ ID NO: 316 to 391, 520 to 530, 546 or 547; and a VL comprising a sequence set forth in any one of SEQ ID NO: 222 to 315 or 515 to 519.

[0318] The present disclosure provides a C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises:

[0319] (i) a VH comprising CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 377, 520 to 530, 546 or 547; and a VL comprising CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 312, 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT; and / or

[0320] (ii) a VH comprising a sequence set forth in any one of SEQ ID NO: 377, 520 to 530, 546 or 547; and a VL comprising a sequence set forth in any one of SEQ ID NO: 312, 515 to 519.

[0321] In one example, the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316 to 391; and the VL comprises CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 222 to 315, wherein the CDRs are defined according to the numbering system of KABAT.

[0322] In one example, the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316 to 391, 520 to 530, 546 or 547; and the VL comprises CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 222 to 315 or 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT.

[0323] In one example, the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 377, 520 to 530, 546 or 547; and the VL comprises CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 312, 515 to 519, wherein the CDRs are defined according to the numbering system of KABAT. In one example, the VH comprises VH comprises a sequence set forth in any one of SEQ ID NO: 316 to 391; and the VL comprises a sequence set forth in any one of SEQ ID NO: 222 to 315.

[0324] In one example, the VH comprises VH comprises a sequence set forth in any one of SEQ ID NO: 316 to 391, 520 to 530, 546 or 547; and the VL comprises a sequence set forth in any one of SEQ ID NO: 222 to 315 or 515 to 519.

[0325] In one example, the VH comprises VH comprises a sequence set forth in any one of SEQ ID NO:377, 520 to 530, 546 or 547; and the VL comprises a sequence set forth in any one of SEQ ID NO: 312, 515 to 519.

[0326] In one example, the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 312 and the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391, wherein the CDRs are defined according to the numbering system of KABAT.

[0327] In one example, the VL comprises a sequence set forth in SEQ ID NO: 312 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391.

[0328] In one example, the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 222 and the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389, wherein the CDRs are defined according to the numbering system of KABAT.

[0329] In one example, the VL comprises a sequence set forth in SEQ ID NO: 222 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389.

[0330] In one example, the VL comprises a sequence set forth in SEQ ID NO: 312 and the VH comprises a sequence set forth in any one of SEQ ID NOs: 546 or 547.

[0331] In one example, the VL comprises a sequence set forth in SEQ ID NO: 515 and the VH comprises a sequence set forth in SEQ ID Ns: 377.

[0332] In one example, the VL comprises a sequence set forth in SEQ ID NO: 516 and the VH comprises a sequence set forth in any one of SEQ ID NOs: 377, 546 or 547.

[0333] In one example, the VL comprises a sequence set forth in SEQ ID NO: 517 and the VH comprises a sequence set forth in any one of SEQ ID NOs: 377, 520 to 530.

[0334] In one example, the VL comprises a sequence set forth in SEQ ID NO: 518 and the VH comprises a sequence set forth in any one of SEQ ID NOs: 377, 522, 523 or 524. In one example, the VL comprises a sequence set forth in SEQ ID NO: 519 and the VH comprises a sequence set forth in SEQ ID NO: 377.

[0335] In one example, the antigen binding domain comprises:

[0336] (i) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107, or

[0337] (ii) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107, or

[0338] (iii) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158, or

[0339] (iv) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158, or

[0340] (v) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158, or

[0341] (vi) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158.

[0342] In one example, the antigen binding domain comprises:

[0343] (i) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159; and a CDR2 comprising a sequence set forth in SEQ ID NO: 165; and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NO: 2; a CDR2 comprising a sequence set forth in any one of SEQ ID NO: 83; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107, and / or

[0344] (ii) a VH comprising a sequence set forth in SEQ ID NO: 316; and a VL comprising a sequence set forth in SEQ ID NO: 222.

[0345] In one example, the antigen binding domain comprises:

[0346] (i) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; and a CDR2 comprising a sequence set forth in SEQ ID NO: 171; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NO: 81; a CDR2 comprising a sequence set forth in any one of SEQ ID NO: 84; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158, and / or

[0347] (ii) a VH comprising a sequence set forth in in SEQ ID NO: 377; and a VL comprising a sequence set forth in SEQ ID NO: 312.

[0348] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 3, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 4, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 5, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 85 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 6, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 3, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 160, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 6, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 160, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 3, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 160, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 167 and a CDR3 comprising a sequence set forth in SEQ ID NO: 179; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 180; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 182; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 170 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 185; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 172 and a CDR3 comprising a sequence set forth in SEQ ID NO: 186; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 173 and a CDR3 comprising a sequence set forth in SEQ ID NO: 187; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 188; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 189; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 173 and a CDR3 comprising a sequence set forth in SEQ ID NO: 190; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 180; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 163, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 174 and a CDR3 comprising a sequence set forth in SEQ ID NO: 191; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 168 and a CDR3 comprising a sequence set forth in SEQ ID NO: 179; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 164, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 170 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 191; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 7, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 9, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 109. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 10, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 110. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 11, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 111. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 12, a CDR2 comprising a sequence set forth in SEQ ID NO: 88 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 13, a CDR2 comprising a sequence set forth in SEQ ID NO: 89 and a CDR3 comprising a sequence set forth in SEQ ID NO: 113. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 14, a CDR2 comprising a sequence set forth in SEQ ID NO: 90 and a CDR3 comprising a sequence set forth in SEQ ID NO: 114. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 15, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 115. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 16, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 116. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 17, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 18, a CDR2 comprising a sequence set forth in SEQ ID NO: 91 and a CDR3 comprising a sequence set forth in SEQ ID NO: 117. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 19, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 118. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 20, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 119. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 21, a CDR2 comprising a sequence set forth in SEQ ID NO: 92 and a CDR3 comprising a sequence set forth in SEQ ID NO: 118. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 22, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 115. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 23, a CDR2 comprising a sequence set forth in SEQ ID NO: 93 and a CDR3 comprising a sequence set forth in SEQ ID NO: 120. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 24, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 121. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 25, a CDR2 comprising a sequence set forth in SEQ ID NO: 95 and a CDR3 comprising a sequence set forth in SEQ ID NO: 122. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 26, a CDR2 comprising a sequence set forth in SEQ ID NO: 96 and a CDR3 comprising a sequence set forth in SEQ ID NO: 123. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 27, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 28, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 124. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 29, a CDR2 comprising a sequence set forth in SEQ ID NO: 97 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 30, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 91 and a CDR3 comprising a sequence set forth in SEQ ID NO: 114. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 32, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 125. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 33, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 126. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 34, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 127. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 35, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 36, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 128. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 37, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 16, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 129. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 130. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 38, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 125. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 39, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 131. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 40, a CDR2 comprising a sequence set forth in SEQ ID NO: 100 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 41, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 132. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 42, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 25, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 134. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 43, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 125. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 44, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 130. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 45, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 112. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 46, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 117. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 47, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 130. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 48, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 126. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 49, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 135. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 50, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 136. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 51, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 137. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 52, a CDR2 comprising a sequence set forth in SEQ ID NO: 101 and a CDR3 comprising a sequence set forth in SEQ ID NO: 138. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 53, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 139. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 54, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 55, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 56, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 58, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 141. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 59, a CDR2 comprising a sequence set forth in SEQ ID NO: 103 and a CDR3 comprising a sequence set forth in SEQ ID NO: 142. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 60, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 143. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 61, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 144. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 62, a CDR2 comprising a sequence set forth in SEQ ID NO: 104 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 63, a CDR2 comprising a sequence set forth in SEQ ID NO: 105 and a CDR3 comprising a sequence set forth in SEQ ID NO: 145. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 64, a CDR2 comprising a sequence set forth in SEQ ID NO: 91 and a CDR3 comprising a sequence set forth in SEQ ID NO: 146. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 20, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 147. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 65, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 148. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 66, a CDR2 comprising a sequence set forth in SEQ ID NO: 106 and a CDR3 comprising a sequence set forth in SEQ ID NO: 125. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 67, a CDR2 comprising a sequence set forth in SEQ ID NO: 90 and a CDR3 comprising a sequence set forth in SEQ ID NO: 126. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 68, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 149. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 69, a CDR2 comprising a sequence set forth in SEQ ID NO: 98 and a CDR3 comprising a sequence set forth in SEQ ID NO: 150. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 70, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 151. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 71, a CDR2 comprising a sequence set forth in SEQ ID NO: 95 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 50, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 152. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 72, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 73, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 153. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 74, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 154. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 75, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 155. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 76, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 117. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 77, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 156. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 78, a CDR2 comprising a sequence set forth in SEQ ID NO: 94 and a CDR3 comprising a sequence set forth in SEQ ID NO: 113. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 80, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 61, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 157. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 82, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 156. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 31, a CDR2 comprising a sequence set forth in SEQ ID NO: 92 and a CDR3 comprising a sequence set forth in SEQ ID NO: 115. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 108. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57, a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79, a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 176 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8, a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 197; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 199; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 202; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 184; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 203; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 178; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 204; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 181; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 166 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 193; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 57 a CDR2 comprising a sequence set forth in SEQ ID NO: 102 and a CDR3 comprising a sequence set forth in SEQ ID NO: 140. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 79 a CDR2 comprising a sequence set forth in SEQ ID NO: 87 and a CDR3 comprising a sequence set forth in SEQ ID NO: 133. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 8 a CDR2 comprising a sequence set forth in SEQ ID NO: 86 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 205; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2 a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 165 and a CDR3 comprising a sequence set forth in SEQ ID NO: 207; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 2 a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 208; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 209; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 210; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 211; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 212; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 213; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81 a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 500 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 513; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 514; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 513; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 514; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 502 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 507 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 508 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 503 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 509 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 510 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 504 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 511 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 505 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 512 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 506 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 171 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 504 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 505 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161, a CDR2 comprising a sequence set forth in SEQ ID NO: 506 and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 498, a CDR2 comprising a sequence set forth in SEQ ID NO: 499 and a CDR3 comprising a sequence set forth in SEQ ID NO: 501.

[0349] In one example, the antigen binding domain comprises:

[0350] (i) a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NO: 222 to 315, or

[0351] (ii) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 478; and a CDR2 comprising a sequence set forth in SEQ ID NO: 479; and a CDR3 comprising a sequence set forth in SEQ ID NO: 480; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 396 to 415; a CDR2 comprising an amino acid sequence ED or DD; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216, wherein the CDRs are defined according to the numbering system of IMGT.

[0352] In one example of any disclosure herein, the CDRs are defined according to the numbering system of IMGT wherein the VH comprises a CDR1 comprising amino acid residues 26 to 33 of any VH sequence described herein; a CDR2 comprising amino acid residues 51 to 58 of any VH sequence described herein; a CDR3 comprising amino acid residues 97 to 114 of any VH sequence described herein; and the VL comprises a CDR1 comprising amino acid residues 26 to 33 of any VL sequence described herein; a CDR2 comprising amino acid residues 51 to 52 of any VL sequence described herein; and a CDR3 comprising amino acid residues 90 to 100 of any VL sequence described herein.

[0353] In one example, the VH comprises a CDR1, CDR2 and CDR3 from one sequence of any one of the sequences of the disclosure, wherein the CDRs are defined according to the numbering system of IMGT. In another example, the VL comprises a CDR1, CDR2 and CDR3 from one sequence of any one of the sequences of the disclosure, wherein the CDRs are defined according to the numbering system of IMGT.

[0354] In one example, the antigen binding domain comprises a VH comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of a VL sequence set forth in any one of SEQ ID NO: 222 to 315 wherein the CDRs are defined according to the numbering system of IMGT.

[0355] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 478; and a CDR2 comprising a sequence set forth in SEQ ID NO: 479; and a CDR3 comprising a sequence set forth in SEQ ID NO: 480; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 396 to 415; and a CDR2 comprising an amino acid sequence ED or DD; and a CDR3 comprising a sequence set forth in SEQ ID NO: 216, wherein the CDRs are defined according to the numbering system of IMGT.

[0356] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 478, wherein the amino acid sequence comprises wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) or Histidine (H) or Isoleucine (I) or Serine (S) or Tyrosine (Y) at position 3 and / or Aspartic Acid (D) or Leucine (L) or Asparagine (N) or Threonine (T) or Tyrosine (Y) at position 5 and / or Alanine (A) or Leucine (L) or Serine (S) at position 6.

[0357] In one example, the antigen binding domain comprises a VH comprising a CDR2 comprising a sequence set forth in SEQ ID NO: 479, wherein the amino acid sequence comprises wherein the amino acid sequence comprises Aspartic Acid (D) or Glutamic Acid (E) at position 4 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) at position 7.

[0358] In one example, the antigen binding domain comprises a VH comprising a CDR3 comprising a sequence set forth in SEQ ID NO: 480, wherein the amino acid sequence comprises wherein the amino acid sequence comprises Lysine (K) or Arginine (R) at position 2 and / or Lysine (K) or Arginine (R) at position 3 and / or Aspartic Acid (D) or Glutamic Acid (E) or Glycine (G) or Serine (S) at position 4 and / or Leucine (L) or Tyrosine (Y) at position 6 and / or Phenylalanine (F) or Tryptophan (W) at position 9 and / or Alanine (A) or Glycine (G) or Serine (S) at position 10 and / or Aspartic Acid (D) or Histidine (H) or Leucine (L) or Glutamine (Q) or Tryptophan (W) or Tyrosine (Y) at position 13.

[0359] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 433 to 450; a CDR2 comprising a sequence set forth in any one of SEQ ID NOs: 451 to 454; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 455 to 477; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NOs: 396 to 415; and a CDR2 comprising an amino acid sequence ED orDD; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 416 to 432, wherein the CDRs are defined according to the numbering system of IMGT.

[0360] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0361] 455. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0362] 456. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0363] 457. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0364] 458. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0365] 459. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0366] 460. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0367] 461. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0368] 462. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0369] 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0370] 464. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0371] 465. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0372] 466. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 438, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0373] 467. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 439, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0374] 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 440, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 441, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 442, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0375] 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 442, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0376] 464. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 438, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0377] 468. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 453 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0378] 469. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 442, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 443, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0379] 470. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 439, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0380] 471. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 444, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0381] 472. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 445, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 446, a CDR2 comprising a sequence set forth in SEQ ID NO: 453 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0382] 473. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 447, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 467. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 448, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 442, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 473. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 449, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 450, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 454 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 454 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0383] 474. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0384] 475. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0385] 476. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO:

[0386] 477.

[0387] In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD; and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 420. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 401, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 421. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 402, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 422. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 403, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 423. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 404, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 424. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 405, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 425. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 405, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 425. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 406, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 426. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 407, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 420. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 408, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 427. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 409, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 410, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 428. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 402, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 429. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 411, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 430. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 412, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 431. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 413, a CDR2 comprising an amino acid sequence DD; and a CDR3 comprising a sequence set forth in SEQ ID NO: 432. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 414, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 415, a CDR2 comprising an amino acid sequence ED; and a CDR3 comprising a sequence set forth in SEQ ID NO: 431.

[0388] In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 433, a CDR2 comprising a sequence set forth in SEQ ID NO: 451 and a CDR3 comprising a sequence set forth in SEQ ID NO: 458 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 459 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 460 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 460 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 460 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 460 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 462 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 457 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 456 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 465 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 396, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 466 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 437, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 463 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 420. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 435, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 464 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 397, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 417. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 420. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 436, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 455 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 416. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 400, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 420. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 398, a CDR2 comprising an amino acid sequence DD and a CDR3 comprising a sequence set forth in SEQ ID NO: 418. In one example, the antigen binding domain comprises a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 434, a CDR2 comprising a sequence set forth in SEQ ID NO: 452 and a CDR3 comprising a sequence set forth in SEQ ID NO: 461 and a VL comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 399, a CDR2 comprising an amino acid sequence ED and a CDR3 comprising a sequence set forth in SEQ ID NO: 419. In one example, the antigen binding domain comprises a VH comp...

Claims

CLAIMS1. A complement C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises:(i) a light chain variable region (VL) comprising: a. a complementarity determining region (CDR)1 comprising a sequence set forth in SEQ ID NO: 2, a CDR2 comprising a sequence set forth in SEQ ID NO: 83 and a CDR3 comprising a sequence set forth in SEQ ID NO: 107, or b. a CDR1 comprising a sequence set forth in SEQ ID NO: 81, a CDR2 comprising a sequence set forth in SEQ ID NO: 84 and a CDR3 comprising a sequence set forth in SEQ ID NO: 158; and(ii) a heavy chain variable region (VH) comprising CDRs 1, 2 and 3 of a VH sequence set forth in any one of SEQ ID NO: 316 to 391, wherein the CDRs are defined according to the numbering system of KABAT.

2. The C2-binding protein of claim 1, wherein:(i) the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 312 and the VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391, wherein the CDRs are defined according to the numbering system of KABAT; and / or(ii)the VL comprises a sequence set forth in SEQ ID NO: 312 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 329, 346, 347, 359, 361, 363, 369, 374 to 379, 383, 385 to 388, 390, and 391.

3. The C2-binding protein of claim 1, wherein:(i) the VL comprises CDRs 1, 2 and 3 of a sequence set forth in SEQ ID NO: 222 and VH comprises CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389, wherein the CDRs are defined according to the numbering system of KABAT; and / or(ii)the VL comprises a sequence set forth in SEQ ID NO: 222 and the VH comprises a sequence set forth in any one of SEQ ID NO: 316, 320, 321, 323 to 326, 328 to 333, 335 to 337, 339, 341 to 347, 350 to 352, 359 to 364, 369, 373, 380, and 389.

4. A C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises:(i) a VH comprising CDRs 1, 2 and 3 of one VH sequence selected from any one of SEQ ID NO: 316 to 391; and a VL comprising CDRs 1, 2 and 3 of one VL sequence selected from any one of SEQ ID NO: 222 to 315, wherein the CDRs are defined according to the numbering system of KABAT; and / or(ii) a VH comprising a sequence set forth in any one of SEQ ID NO: 316 to 391; and a VL comprising a sequence set forth in any one of SEQ ID NO: 222 to 315.

5. The C2-binding protein of any one of claims 1 to 4, wherein the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 at acidic and neutral pH and neutralizes C2b catalytic activity.

6. The C2-binding protein of any one of claims 1 to 5, wherein the C2-binding protein binds to C2 and C2b at pH 7.4 with an affinity which is at least 2-fold greater or at least 10-fold greater than a protein comprising an antigen binding domain comprising a heavy chain variable region (VH) of SEQ ID NO: 316 and a light chain variable region (VL) of SEQ ID NO: 222.

7. The C2-binding protein of any one of claims 1 to 6, wherein the C2-binding protein inhibits the classical complement pathway and / or the lectin complement pathway with an IC50 of 50 nM or less, or 25 nM or less, or 15 nM or less, or 10 nM or less, or 5 nM or less, or 1 nM or less, wherein the IC50 is determined by a complement assay and / or by a hemolytic assay.

8. The C2-binding protein of any one of claims 1 to 7, wherein:(i) the KD of the C2-binding protein for a C2 polypeptide comprising a sequence set forth in SEQ ID NO: 1 at pH 7.4 is about 10 nM or less, and(ii)the KD of the C2-binding protein for a C2b polypeptide comprising a sequence set forth in SEQ ID NO: 481 at pH 7.4 is about 20 nM or less.

9. The C2-binding protein of any one of claims 1 to 8, wherein the antigen binding domain specifically binds to an epitope within a serine protease domain of C2 comprising one or more or all amino acids corresponding to residues 538, 541, 625, 628, 656, 681, 686, 695 of SEQ ID NO: 1.

10. The C2-binding protein of any one of claims 1 to 9, wherein the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1 in which an alanine is substituted for one of:(i) lysine at position 656 of SEQ ID NO: 1;(ii) lysine at position 695 of SEQ ID NO: 1;(iii) leucine at position 681 of SEQ ID NO: 1;(iv) leucine at position 686 of SEQ ID NO: 1;(v) tyrosine at position 538 of SEQ ID NO: 1;(vi) methionine at position 628 of SEQ ID NO: 1;(vii) glutamic acid at position 625 of SEQ ID NO: 1, is lower than the affinity of the C2-binding protein to a C2 polypeptide of SEQ ID NO: 1.

11. The C2-binding protein of any one of claims 1 to 10, wherein the C2-binding protein does not detectably bind to a C2 polypeptide comprising an alanine substitution at position 681 and / or 695 and / or 538 of SEQ ID NO: 1.

12. The C2-binding protein of claim 3, wherein the antigen binding domain comprises:(i) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 159; and a CDR2 comprising a sequence set forth in SEQ ID NO: 165; and a CDR3 comprising a sequence set forth in SEQ ID NO: 177; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NO: 2; a CDR2 comprising a sequence set forth in any one of SEQ ID NO: 83; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 107, and / or(ii) a VH comprising a sequence set forth in SEQ ID NO: 316; and a VL comprising a sequence set forth in SEQ ID NO: 222.

13. A complement C2-binding protein comprising an antigen binding domain of an antibody, wherein the antigen binding domain comprises a light chain variable region (VL) having a sequence set forth in SEQ ID NO:531, wherein positions 31, 52, 53 and 93 each comprise a residue independently selected from Aspartic Acid (D) and Glutamic Acid (E); and further comprising a heavy chain variable region (VH) having a sequence set forth in SEQ ID NO:533, wherein the amino acid sequence comprises Serine (S) or Leucine (L) at position 56, Leucine (L) or Threonine (T) at position 58, Arginine (R) or Lysine(K), and wherein positions 54, 55, 57, 110, 113 each comprise a residue independently selected from Aspartic Acid (D) and Glutamic Acid (E).

14. The C2-binding protein of claim 2, wherein the antigen binding domain comprises:(i) a VH comprising a CDR1 comprising a sequence set forth in SEQ ID NO: 161; and a CDR2 comprising a sequence set forth in SEQ ID NO: 171; and a CDR3 comprising a sequence set forth in SEQ ID NO: 198; and a VL comprising a CDR1 comprising a sequence set forth in any one of SEQ ID NO: 81; a CDR2 comprising a sequence set forth in any one of SEQ ID NO: 84; and a CDR3 comprising a sequence set forth in any one of SEQ ID NOs: 158, and / or(ii) a VH comprising a sequence set forth in in SEQ ID NO: 377; and a VL comprising a sequence set forth in SEQ ID NO: 312.

15. The C2-binding protein of any one of claims 1 to 14, wherein the VH comprises one or more modifications in a framework region, wherein the modification comprises:(i) a valine (V) at an amino acid corresponding to position 18 of SEQ ID NO: 316, a valine (V) at amino acid corresponding to position 20 of SEQ ID NO: 316, an alanine (A) at an amino acid corresponding to position 24 of SEQ ID NO: 316, an alanine (A) at an amino acid corresponding to position 40 of SEQ ID NO: 316; and a glutamine (Q) at an amino acid corresponding to position 43 of SEQ ID NO: 316; or(ii) a valine (V) at an amino acid corresponding to position 18 of SEQ ID NO: 316, a valine (V) at amino acid corresponding to position 20 of SEQ ID NO: 316, an alanine (A) at an amino acid corresponding to position 24 of SEQ ID NO: 316, and an alanine (A) at an amino acid corresponding to position 40 of SEQ ID NO: 316; or(iii) an alanine (A) at an amino acid corresponding to position 40 of SEQ ID NO: 316; and a glutamine (Q) at an amino acid corresponding to position 43 of SEQ ID NO: 316; or(iv) an alanine (A) at an amino acid corresponding to position 40 of SEQ ID NO: 316.

16. The C2-binding protein of any one of claims 1 to 15, wherein the C2-binding protein comprises an Fc region.

17. The C2-binding protein of claim 16, wherein the C2-binding protein is an anti-C2 antibody.

18. The C2-binding protein of claim 16 or 17, wherein the Fc region comprises one or more amino acid substitutions which increases the C2-binding protein’s affinity to neonatal Fc receptor (FcRn).

19. The C2-binding protein of claims 16 to 18, wherein the Fc region comprises one or more amino acid substitutions selected from S228P, L234A, F234A, L235A, P329G, M252Y, S254T, T256E, V308P, N286E, M428L, N434A, and N434Y according to the EU numbering system.

20. The C2-binding protein of claim 19, wherein the Fc region comprises the following amino acid substitutions:(i) M252Y, V308P, N434Y;(ii) M252Y, S254T, T256E; or(iii)M252Y, N286E, N434Y; and optionally one or more of the following amino acid substitutions:(i) L234A, L235A;(ii) F234A, L235A;(iii)L234A, L235A, P329G; or(iv)F234A, L235A, P329G, wherein the amino acid position is according to the EU numbering system.

21. The C2-binding protein of any one of claims 16 to 20, wherein the antigen binding domain binds C2 at neutral pH and optionally at acidic pH and the Fc region comprises the following amino acid substitutions M252Y, V308P, and N434Y according to the EU numbering system.

22. The C2-binding protein of any one of claims 1 to 21, wherein the C2-binding protein is an anti-C2 antibody comprising:(i) a heavy chain comprising a sequence set forth in SEQ ID NO: 485; and(ii) a light chain comprising a sequence set forth in SEQ ID NO: 484.

23. A composition comprising the C2-binding protein of any one of claims 1 to 22, or an antibody having the same CDRs as the antigen binding domain of the C2-binding protein of any one of claims 1 to 22 and a pharmaceutically acceptable carrier.

24. A method of inhibiting complement activity in a subject and / or treating or preventing a complement-mediated disorder in a subject, the method comprising administering the C2-binding protein of any one of claims 1 to 22 or the composition of claim 23 to the subject.

25. The method of claim 24, wherein the complement-mediated disorder is selected from the group consisting of transplant rejection (including delayed graft function, graft salvage and antibody mediated rejection), a nephropathy, ischemia-reperfusion injury, neuromyelitis optica, myasthenia gravis, a glomerular pathology, lupus nephritis (acute and chronic), IgA nephropathy, bullous pemphigoid, anti-phospholipid syndrome, uveitis, a neurological disorder, Parkinson’s disease, Huntington’s disease, cerebral infarction, motor neuron disease, autoimmune haemolytic anemia, ANCA-associated vasculitis, chronic inflammatory demyelinating polyneuropathy, ischemic stroke (with and without reperfusion), traumatic brain injury, somatic trauma, anti-glomerular basement membrane (GBM) nephritis, multifocal motor neuropathy (MMN), dermatomyositis (DM), systemic lupus erythematosus (SLE), autoimmune hemolytic anemia (AIHA), warm autoimmune hemolytic anemia (wAIHA), immune thrombocytopenia (ITP), neuromyelitis optica spectrum disorder (NMOSD), membranous nephropathy (MN), primary membranous nephropathy (MN), antibody- mediated rejection (AMR), atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), cold agglutinin disease (CAD), anti-phospholipid syndrome (APS), inclusion body myositis (IBM), Sjogren's syndrome (SjS), hidradenitis suppurativa (HS), immune-mediated necrotizing myopathy (IMNM), anti synthetase syndrome (ASyS) and combinations thereof.

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