Anti-sars-cov-2 antigen binding polypeptides, polypeptide complexes and methods of use thereof

Abstract

Disclosed are antigen binding antigen binding polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural and / or functional features. Also disclosed are polynucleotides and vectors encoding such polypeptide complexes; host cells, pharmaceutical compositions and kits containing such polypeptide complexes; and methods of using such polypeptide complexes.

Description

ANTI-SARS-COV-2 ANTIGEN BINDING POLYPEPTIDES, POLYPEPTIDE COMPLEXES AND METHODS OF USE THEREOFCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. Provisional Application No. 63 / 357,336, filed June 30, 2022; U.S. Provisional Application No. 63 / 357,873, filed July 1, 2022; U.S. Provisional Application No. 63 / 404,473, filed September 7, 2022; U.S. Provisional Application No. 63 / 381,850, filed November 1, 2022; and U.S. Provisional Application No. 63 / 433,719, filed December 9, 2022; which are all incorporated herein by reference in their entireties.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The content of the electronically submitted sequence listing (Name: 4850_0100003_SEQLISTING_ST26.xml; Size: 486,871 bytes; Date of Creation: June 28, 2023) is herein incorporated by reference in its entirety.FIELD

[0003] The present disclosure relates to anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antigen binding polypeptides and polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural and / or functional features. The present disclosure also relates to polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells; pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0004] This invention was made in the performance of a Cooperative Research andDevelopment Agreement with the National Institutes of Health, an Agency of theDepartment of Health and Human Services. The Government has certain rights in this invention.BACKGROUND

[0005] The outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused over 450 million infections and over 6 million deaths worldwide.SARS-CoV-2 is the strain of coronavirus that causes COVID-19 (coronavirus disease 2019). Sequencing and publication of the original Wuhan Hu-1 (WA-1) genome enabled rapid vaccine design and production of spike proteins for therapeutic antibody development. However, persistent circulation of viruses during human pandemics leads to genetic variation that resists containment and eradication. While cellular and humoral immune responses are needed for optimal protection against viral infection, neutralizing antibodies play a major role in prevention and eradication of pathogens.

[0006] SARS-CoV-2 spike protein mutants and SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P. l), Delta (B.1.617.2), Epsilon variant (B.1.427), and Omicron (B.1.1.529) have emerged to contain mutations that are resistant to current therapies, have increased pathogenicity, and evade current vaccines. This led to their classification as variants of concern (VOCs).

[0007] Therapeutic antibodies have emerged as an important class of agents for treating human diseases and disorders. Therapeutic antibodies have been engineered to have specificity for two or more different antigens or epitopes (i.e., "multispecific" antibodies that are, for example, bispecific, trispecific or tetraspecific). Multispecific antibodies have been used to form multi-targeting strategies to treat human diseases and disorders, and are an important technological platform for developing neutralizing antibody -based therapeutics for preventing and treating SARS-CoV-2 infection and COVID-19.

[0008] There is a need for improved therapies to prevent and treat SARS-CoV-2 infection and COVID-19. There is a need for therapeutic antibodies with broad VOC reactivity and resistance to SARS-CoV-2 escape. There is also a need for therapeutic antibodies that are easier to manufacture and administer than current therapeutic antibody cocktails. There is also a need to treat or prevent SARS-CoV-2 infection and COVID-19 in immunocompromised individuals who cannot mount an effective immune response through vaccinations.BRIEF SUMMARY

[0009] Provided herein is an antigen binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by VL1-L1-CL; wherein the second polypeptide has a structure represented by VH1-L2-CH1; wherein the third polypeptide has a structure represented by VH2-L3-VH3-L4-CH1; wherein the fourth polypeptide has a structure represented by VL3-L5-VL2-L6-CL; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS- CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; CHI is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-L6 are amino acid linkers.

[0010] Also provided herein is an antigen binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by VL1-L1-CL; wherein the second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; wherein the third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; wherein the fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS- CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chainconstant region 3 (CH3), and optionally, an immunoglobulin hinge; CHI is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-L8 are amino acid linkers.

[0011] In some aspects, VH1 comprises the same heavy chain variable region as VH3, and VL1 comprises the same light chain variable region as VL3.

[0012] In some aspects, VH1 comprises the same heavy chain variable region as VH2, and VL1 comprises the same light chain variable region as VL2.

[0013] In some aspects, VH2 comprises the same heavy chain variable region as VH3, and VL2 comprises the same light chain variable region as VL3.

[0014] In some aspects, VH1, VH2 and VH3 each comprise the same heavy chain variable region, and VL1, VL2 and VL3 each comprise the same light chain variable region.

[0015] In some aspects, VH1, VH2 and VH3 each comprise different heavy chain variable regions, and V 1, VL2 and VL3 each comprise different light chain variable regions.

[0016] In some aspects, VH1, VH2 and VH3 each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241, 249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243, 251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; and VL1, VL2 and VL3 each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having thesequence of GAS), 31 (having the sequence of DAS), 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence of LGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349.

[0017] In some aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; and VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

[0018] In some aspects, VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%,at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

[0019] In some aspects, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

[0020] In some aspects, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

[0021] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence ofDAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

[0022] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

[0023] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; andVL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

[0024] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence ofGAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16.

[0025] In some aspects, VH1, VH2 and VH3 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs: l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359. In some aspects, the sequence has a mutation at N62, for example, N62Q or N62Q at, for example, SEQ ID NO: 175.

[0026] In some aspects, VL1, VL2 and VL3 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346.

[0027] In some aspects, VH1, VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; and VL1, VL2 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

[0028] In some aspects, VH1 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

[0029] In some aspects, VH1 and VH2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

[0030] In some aspects, VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL2 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

[0031] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

[0032] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having atleast 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

[0033] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

[0034] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13.

[0035] In some aspects, the immunoglobulin hinge comprises an upper hinge region, a middle hinge region, a lower hinge region, or a combination thereof.

[0036] In some aspects, linkers L1-L8 each independently have a length of from about 0 amino acids to about 50 amino acids.

[0037] In some aspects, linkers L1-L8 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or100% identity to any one of SEQ ID NOs:46-80 (wherein SEQ ID NO:47 has the sequence of G, SEQ ID NO:48 has the sequence of A, SEQ ID NO:49 has the sequence of GSS, and SEQ ID NO:50 has the sequence of ASG).

[0038] In some aspects, one or more of linkers L1-L8 are non-immunogenic.

[0039] In some aspects, one or more of linkers L1-L8 do not contain a consensus T cell epitope.

[0040] In some aspects, the Fc region comprises at least one knob-into-hole modification or Fc effector function knockout mutation.

[0041] In some aspects, the antigen binding polypeptide complex is an IgGl or IgG4 antibody and the knob-into-hole modification comprises (i) knob substitutions of S354C and T366W and hole substitutions of Y349C, T366S, L368A and Y407V; (ii) hole substitutions of M428L and N434S or N434A; (iii) hole substitutions of M252Y, S254T and T256E; or (iv) a combination thereof; based on the EU numbering scheme. In some aspects, the hole substitutions are M428L and N434S, based on the EU numbering scheme. In some aspects, the hole substitution is N434A, based on the EU numbering scheme.

[0042] In some aspects, the antigen binding polypeptide complex is an IgGl or IgG4 antibody and the Fc effector function knockout mutation is L234A, L235A, P239A or a combination thereof, based on the EU numbering scheme.

[0043] In some aspects, the antigen binding polypeptide complex comprises a detectable label. In some aspects, the detectable label is a radioactive label, chemiluminescent label, fluorescent label, enzyme, peptide tag, or a combination thereof. In some aspects, the peptide tag is a polyhistidine tag consisting of from about four to about 10 histidine residues. In some aspects, the polyhistidine tag consists of about eight histidine residues.

[0044] In some aspects, the antigen binding polypeptide complex specifically binds to a SARS-CoV-2 protein with an equilibrium dissociation constant (KD) of from about 10 pM to about 1 pM.

[0045] In some aspects, a variable region of an antibody may require site specific deglycosylation. In some aspects, and with respect to E8 VH mAb, an N62 mutation is made to remove a high mannose glycosylate residue or moiety. Preferred mutations include, but are not limited to, N62Q or N62S.

[0046] In some aspects, the SARS-CoV-2 virus is the original Wuhan strain (WAI), D614G spike protein mutant (D614G), Alpha variant (B.1.1.7), Beta variant (B.1.351),Gamma variant (P.l), Kappa variant (B.1.617.1), Delta variant (B.1.617.2 or AY.l), Epsilon variant (B.1.427), Iota variant (B.1.526), Lambda variant (C.37), Mu variant (B.1.621), C.1.2 variant, Omicron variant (BAI.1.529, BA. l, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ. l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ. l, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

[0047] In some aspects, the SARS-CoV-2 protein is a membrane protein, nucleocapsid protein, envelope protein, or spike protein. In some aspects, the SARS-CoV-2 protein is a spike protein.

[0048] Also provided herein is an antibody or antigen binding fragment thereof comprising an antigen binding polypeptide complex provided herein. In some aspects, the antibody is IgG, IgM, IgE, IgA or IgD. In some aspects, the IgG is IgGl, IgG2, IgG3 or IgG4. In some aspects, the antigen binding fragment is a Fab, scFab, Fab', F(ab')2, Fv or scFv. In some aspects, the antibody is human or humanized. In some aspects, the antibody is a monoclonal antibody, grafted antibody, or chimeric antibody.

[0049] Also provided herein is an anti-SARS-CoV2 multivalent antibody that exhibits improved prevention of immune escape compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

[0050] Also provided herein is a pharmaceutical composition comprising an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof provided herein. In some aspects, the pharmaceutical composition comprises (1) one or more polynucleotides encoding an antigen binding polypeptide or antigen binding polypeptide complex and (2) a carrier. In some aspects, the pharmaceutical composition comprises (1) one or more polynucleotides encoding an antigen binding polypeptide or antigen binding polypeptide complex (e.g., antibody or antigen binding fragment thereof) provided herein, and (2) a carrier selected from the group consisting of a lipid or a lipid nanoparticle. In some aspects, the one or more polynucleotides encoding an antigen binding polypeptide or antigen binding polypeptide complex is a stabilized polynucleotide resistant to degradation or decomposition in vivo. In some aspects, the stabilized polynucleotide is capped at one end (5' cap) and has a long poly adenylated (poly A) tail at the other end to form a stabilized mRNA having 5' and 3' UTRs. In some aspects, the polyA tail is about 50 bp, about 100 bp, about 120 bp, orabout 150 bp. In some aspects, modified nucleosides may be incorporated into the mRNA to increase translation and / or to lower potential immunogenicity.

[0051] Also provided herein is a pharmaceutical composition comprising an antigen binding polypeptide complex, antibody, or antigen binding fragment thereof provided herein, and an additional pharmaceutical agent.

[0052] Also provided herein is a kit comprising an antigen binding polypeptide complex, antibody or antigen binding fragment thereof, or pharmaceutical composition provided herein.

[0053] Also provided herein is a method of preventing or treating a SARS-CoV-2 viral infection in a subject in need thereof, comprising administering to the subject an effective amount of an antigen binding polypeptide or polypeptide complex provided herein, an antibody or antigen binding fragment thereof provided herein, a pharmaceutical composition provided herein, or a combination thereof. Delivery of the therapeutic antigen binding polypeptide or antigen binding polypeptide complex can be by direct administration of the therapeutic or by an indirect method that is inclusive of a modified mRNA composition that is administered to the patient in need of treatment thereof by a therapeutic antigen binding polypeptide or antigen binding polypeptide complex translated from the modified mRNA that codes for the therapeutic polypeptide or polypeptide complex.

[0054] Also provided herein is a method of preventing or treating coronavirus disease 2019 (COVID-19) in a subject in need thereof, comprising administering to the subject an effective amount of an antigen binding polypeptide or polypeptide complex provided herein, an antibody or antigen binding fragment thereof provided herein, a pharmaceutical composition provided herein, or a combination thereof.

[0055] Also provided herein is a method of diagnosing a subject as being infected with a SARS-CoV-2 virus or suspected of being infected with a SARS-CoV-2 virus, comprising (i) contacting a sample obtained from the subject with an antigen binding polypeptide or polypeptide complex provided herein or an antibody or antigen binding fragment thereof provided herein; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as being infected with a SARS-CoV-2 virus or suspected of being infected with a SARS-CoV-2 virus when the presence of the virus complex is detected.

[0056] Also provided herein is a method of diagnosing a subject as not being infected with a SARS-CoV-2 virus or not suspected of being infected with a SARS-CoV-2 virus, comprising (i) contacting a sample obtained from the subject with an antigen binding polypeptide or polypeptide complex provided herein or an antibody or antigen binding fragment thereof provided herein; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS- CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as not being infected with a SARS-CoV-2 virus or not suspected of being infected with a SARS-CoV- 2 virus when the presence of the virus complex is not detected.

[0057] Also provided herein is a method of diagnosing a subject as having COVID-19 or suspected of having COVID-19, comprising (i) contacting a sample obtained from the subject with an antigen binding polypeptide or polypeptide complex provided herein or an antibody or antigen binding fragment thereof provided herein; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as having COVID-19 or suspected of having COVID-19 when the presence of the virus complex is detected.

[0058] Also provided herein is a method of diagnosing a subject as not having COVID- 19 or not suspected of having COVID-19, comprising (i) contacting a sample obtained from the subject with an antigen binding polypeptide or polypeptide complex provided herein or an antibody or antigen binding fragment thereof provided herein; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as not having COVID-19 or not suspected of having COVID-19 when the presence of the virus complex is not detected.

[0059] In some aspects, the sample is a nasal swab, tissue sample, saliva, plasma or blood.

[0060] In some aspects, detecting the presence or absence of the virus complex comprises an enzyme linked immunosorbent assay (ELISA), immunospot assay, lateral flow assay, flow cytometry, immunohistochemistry or western blot.

[0061] In some aspects, the SARS-CoV-2 virus is the original Wuhan strain (WAI), D614G spike protein mutant (D614G), Alpha variant (B.1.1.7), Beta variant (B.1.351), Gamma variant (P.1), Kappa variant (B.1.617.1), Delta variant (B.1.617.2 or AY.l),Epsilon variant (B.1.427), Iota variant (B.1.526), Lambda variant (C.37), Mu variant (B.1.621), C.1.2 variant, Omicron variant (BAI.1.529, BA.l, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.l, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

[0062] In some aspects, the SARS-CoV-2 virus is the original Wuhan strain (WAI), D614G spike protein mutant (D614G), Alpha variant (B.1.1.7), Beta variant (B.1.351), Gamma variant (P.l), Kappa variant (B.1.617.1), Delta variant (B.1.617.2 or AY.l), Epsilon variant (B.1.427), Iota variant (B.1.526), Lambda variant (C.37), Mu variant (B.1.621), C.1.2 variant, Omicron variant (BAL 1.529, BA.l, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.l, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

[0063] Also provided herein is a method of preventing immune escape of a SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an antigen binding polypeptide or polypeptide complex provided herein, an antibody or antigen binding fragment thereof provided herein, a pharmaceutical composition provided herein, or a combination thereof.

[0064] Also provided herein is a method of preventing immune escape of a SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an anti-SARS-CoV2 multivalent antibody that exhibits improved prevention of immune escape compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

[0065] Also provided herein is a method of neutralizing a SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an antigen binding polypeptide or polypeptide complex provided herein, an antibody or antigen binding fragment thereof provided herein, or a combination thereof.

[0066] Also provided herein is a method of increasing neutralization potency against a SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an antigen binding polypeptide or polypeptide complex provided herein, an antibody or antigen binding fragment thereof provided herein, or a combination thereof.

[0067] Also provided herein is a method of increasing neutralization potency against a SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an anti-SARS-CoV2 multivalent antibody that exhibits increased neutralization potency compared to (i) a monovalent anti- SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Some aspects of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of aspects of the invention.

[0069] FIG. 1 shows an exemplary configuration of a monospecific, trivalent cross-over dual variable (CODV) immunoglobulin antibody made utilizing variable fragments (Fv) from the anti -SARS-CoV-2 antibody, Bl-182.1 (Fvl82.1, dotted). The Fc region contains a knob-into-hole modification to increase yield and correct association of heavy chains.

[0070] FIG. 2A-2C shows exemplary configurations of bispecific, trivalent CODV immunoglobulin antibodies made utilizing variable fragments (Fv) from Bl-182.1 (Fvl82.1, dotted) and the anti-SARS-CoV-2 antibody, A19-61.1 (Fv61.1, grid). The Fc region contains a knob-into-hole modification to increase yield and correct association of heavy chains.

[0071] FIG. 3A-3D shows exemplary configurations of trispecific, trivalent CODV immunoglobulin antibodies made utilizing variable fragments (Fv) from Bl-182.1 ("182.1" or "Fvl82 Class I", dotted), the anti-SARS-CoV-2 antibody, A19-46.1 ("46.1" or "Fv46 Class II", striped) and A19-61.1 ("61.1" or "Fv61 Class III", grid). The Fc region contains a knob-into-hole modification to increase yield and correct association of heavy chains.

[0072] FIG. 4A shows purity of CODV immunoglobulin antibodies evaluated under non- reducing (nr) and reducing (r) conditions on a Coomassie SDS-PAGE gel (representative gels shown). A molecular weight marker standard (MW) is also shown.

[0073] FIG. 4B shows CODV immunoglobulin bispecific and trispecific antibody traces shown before (top row) and after size exclusion chromatography (SEC) (bottom row). The dotted box indicates the fractions combined to make final preparations of the indicated multispecific antibodies. The bottom row shows analytic SEC traces for the purified multispecific antibodies.

[0074] FIG. 5A shows cross-over dual variable immunoglobulin antibody designs used in FIGs. 5B-5E and Table 4.

[0075] FIG. 5B shows the expected binding of Fvl82.1 ("Fvl82"), Fv46.1 ("Fv46"), and Fv61.1 ("Fv61") to viral spike receptor-binding domain (RBD) proteins containing the indicated Fv isolating mutations, that were selected to knockout binding a single component Fv while leaving binding of the remain Fv components unchanged.

[0076] FIG. 5C-5E shows validation of multispecific Fv binding activity using Fv isolating mutations in RBD and enzyme-linked immunosorbent assay (ELISA). Shown is ELISA binding for parental component antibody controls (FIG. 5C, B 1-182.1, Al 9-46.1, and Al 9-61.1), bispecific antibodies (FIG. 5D, 182.1 / 182.1-61.1, 182.1 / 61.1-182.1, 61.1 / 182.1-182.1, 61.1 / 61.1-182.1 and 61.1 / 182.1-61.1), and trispecific antibodies (FIG. 5E, 46.1 / 61.1-182.1, 46.1 / 182.1-61.1, 61.1 / 46.1-182.1 and 61.1 / 182.1-46.1) against WA- 1 RBD (wt) or RBD proteins containing one or more Fv-specific mutation shown and chosen to interrogate binding of one Fv component at a time in each multispecific antibody.

[0077] FIG. 6A shows a schematic illustration of arrangement of antibody variable domains in different CODVs. The domains are dotted, striped, grid, and gray for Fvl82.1 (182.1), Fv46.1 (46.1), Fv61.1 (61.1) and constant domains, respectively.

[0078] FIG. 6B shows combinations of RBD mutations on the SARS-CoV-2 spike designed to distinguish different binding modes of CODV.

[0079] FIG. 6C is a schematic of CODV 61.1-182.1 (left) and binding of the CODV 61.1-182.1 to spike protein mutants (middle left and right). For clarity, the Fv domain that is not able to bind to the mutant is colored black. CODV binding to K444E / L452R mutant was observed, indicating CODV 61.1-182.1 can bind to spike protein through Fvl82 domain (middle left). However, no CODV was observed to bind the L452R / F486S mutant (middle right), suggesting that the CODV 61.1-182.1 cannot bind through the Fv61 domain in the trimer context. A model of the CODV 61.1-182.1 bound to the SARS-CoV-2 spike protein is shown in the allowed Fvl82-binding mode (right).For clarity, only one CODV is shown to bind to the spike protein in RBD-up conformation. The white scale bar represents 10 nm.

[0080] FIG. 6D is a schematic of CODV 182.1-61.1 (left) and binding of the CODV182.1-61.1 to spike protein mutants (middle left and right). For clarity, the Fv domain that is not able to bind to the mutant is colored black. CODV was observed to bind both K444E / L452R and L452R / F486S mutants, indicating the CODV 182.1-61.1 can bind to spike protein through either Fvl82 domain (middle left) or Fv61 domain (middle right). Models of the CODV 182.1-61.1 bound to the SARS-CoV-2 spike protein are shown in both Fvl82.1-binding and Fv61.1 -binding modes (right). The scale is the same as in FIG. 6C

[0081] FIG. 6E is a schematic of CODV 46.1-182.1 (left) and binding of the CODV46.1-182.1 to spike protein mutants (middle left and right). For clarity, the Fv domain that is not able to bind to the mutant is colored black. CODV was observed to bind both K444E / L452R and K444E / F486S mutants, indicating the CODV 46.1-182.1 can bind to the spike protein through both Fvl82 and Fv46 domains (middle left and right). Models of the CODV 46.1-182.1 bound to the SARS-CoV-2 spike protein are shown to bind through Fvl82 and Fv46-binding modes (right). The scale is the same as in FIG. 6C.

[0082] FIG. 6F is a schematic of CODV 182.1-46.1 (left) and binding of the CODV182.1-46.1 to spike protein mutants (middle left and right). For clarity, the Fv domain that is not able to bind to the mutant is colored black. CODV was observed to bind K444E / L452R, indicating the CODV 182.1-46.1 can bind to the spike protein through the Fvl82.1 domain (middle left). However, no CODV was observed to bind the K444E / F486S mutant (middle right), suggesting that the CODV 182.1-46.1 cannot bind through the Fv46 domain in the trimer context. Model of the CODV 182.1-46.1 bound to the SARS-CoV-2 spike protein is shown to bind through the allowed Fvl82 domain (right). The scale is the same as in FIG. 6C.

[0083] FIG. 6G shows CODV 46.1-182.1- and 182.1-46.1 -induced aggregation of the Omicron spike protein using negative stain-electron microscopy (NSEM).

[0084] FIG. 6H shows the spike-aggregating potential of 61.1 / 46.1-182.1 using NSEM.

[0085] FIG. 7 shows SARS-CoV-2 escape potential by single antibodies, combinations of single antibodies, and candidate multispecific antibodies.

[0086] FIG. 8 shows results from three independent experiments showing SARS-CoV-2 escape potential of T3 V3 (having 61.1, 46.1 and 182.1 binding regions), compared to anantibody having binding regions for 182.1, 61.1 and 46.1 (182.1+61.1+46.1); an antibody having binding regions for 182.1 (182.1); bebtelovimab (LY1404); and an AZD7442 cocktail (2196+2130).

[0087] FIG. 9 shows the resulting serum concentration of E8 glycosylation mutant antibodies in pg / mL, at days 1, 2, 5, 7, 9, 14, 21, 28 and 35, following infusion of mice at 5 mg antibody / kg of body weight.DETAILED DESCRIPTION OF THE INVENTION

[0088] Provided herein are antigen binding polypeptides and polypeptide complexes having improved features. In some aspects, the antigen binding polypeptides and polypeptide complexes have broad reactivity against SARS-CoV-2 variants of concern (VOCs), high neutralization potency, and / or resistance to SARS-CoV-2 escape. In some aspects, the antigen binding polypeptides and polypeptide complexes provided herein are easier to manufacture and administer than current therapeutic antibody cocktails. In some aspects, the antigen binding polypeptides and polypeptide complexes treat and / or prevent SARS-CoV-2 infection and / or COVID-19 in immunocompromised individuals who cannot mount an effective immune response through vaccinations.

[0089] Various terms relating to aspects of disclosure are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art, unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein.Definitions

[0090] As used herein, the term "SARS-CoV-2" refers to "severe acute respiratory syndrome coronavirus 2." SARS-CoV-2 is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19).

[0091] As used herein, the term "SARS-CoV-2 virus" includes the SARS-CoV-2 virus, virion or fragment thereof.

[0092] As used herein, the term "COVID-19" refers to "coronavirus disease 2019." COVID-19 is caused by the SARS-CoV-2 virus. Symptoms of COVID-19 are variable, but often include fever, cough, headache, fatigue, breathing difficulties, loss of smell, and loss of taste. Symptoms may begin one to fourteen days after exposure to the virus;however, at least a third of people who are infected do not develop noticeable symptoms. Of those people who develop symptoms noticeable enough to be classed as patients, most develop mild to moderate symptoms (up to mild pneumonia), with approximately 15% developing severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and approximately 5% suffering critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Some people continue to experience a range of effects for months after recovery ("long COVID").

[0093] As used herein, the term "SARS-CoV-2 protein" refers to any protein related to the SARS-CoV-2 virus. The SARS-CoV-2 virus is made of 16 non- structural proteins and four structural proteins. The non- structural proteins are involved mainly in virus replication. The structural proteins include the membrane protein, nucleocapsid protein, envelope protein, and spike protein, which are involved in assembly and infection of the virus. The spike protein has two subunits, SI and S2, which are responsible for the specific recognition of human angiotensin converting enzyme 2 (hACE2) on the surface of host cells and viral entry. SI specifically binds the hACE2 through its receptor- binding domain (RBD), whereas S2 facilitates the fusion of the virus to the cell membrane. As such, as used herein, a SARS-CoV-2 protein includes, but is not limited to, a membrane protein, nucleocapsid protein, envelope protein, or spike protein, or a combination thereof. In some aspects, the SARS-CoV-2 protein is a spike protein.

[0094] In some aspects, an antigen binding polypeptide or antigen binding polypeptide complex provided herein (e.g., an antibody or antigen binding fragment thereof) is, or is part of, a class I antibody, a class II antibody, or a class III antibody.

[0095] As used herein, "class I" refers to an antibody that typically contains a short heavy chain CDR3 region and competes with angiotensin-converting enzyme 2 (ACE2) for binding to the receptor binding domain (RBD) of the spike protein, and only recognizes the "up" configuration of the RBD. See, e.g., Shrestha et al., Front. Immunol. 12:7520003, 2021. As used herein, "class II" refers to an antibody that typically has a long heavy chain CDR3 loop, competes with ACE2 for binding to RBD, and is capable of binding to RBD in both the "up" and "down" configurations. As used herein, "class III" refers to an antibody that is capable of binding to RBD in both the "up" and "down" configurations and typically binds outside of the ACE2 binding region. As used herein, "class IV" refers to an antibody that binds to the highly conserved, cryptic epitope on RBD outside the receptor binding motif (RBM) of the spike protein.

[0096] In some aspects, an antigen binding polypeptide or antigen binding polypeptide complex provided herein (e.g., an antibody or antigen binding fragment thereof) belongs to two, three or four classes. Accordingly, in some aspects, an antigen binding polypeptide or antigen binding polypeptide complex provided herein (e.g., an antibody or antigen binding fragment thereof) is a class I and II antibody, class I and III antibody, class I and IV antibody, class II and III antibody, class II and IV antibody, class III and IV antibody, class I, II and III antibody, class I, II and IV antibody, class I, III and IV antibody, class II, III and IV antibody, or class I, II, III and IV antibody.

[0097] In some aspects, an antigen binding polypeptide or antigen binding polypeptide complex provided herein comprises one or more class I antigen binding sites, one or more class II antigen binding sites, and / or one or more class III antigen binding sites. In some aspects, VH1 and VL1 and / or VH3 and VL3 are class III antigen binding sites. In some aspects, VH2 and VL2 and / or VH4 and VL4 are class I antigen binding sites. In some aspects, VH1, VL1, VH3 and VL3 are class III antigen binding sites and VH2, VL2, VH4 and VL4 are class I antigen binding sites. In some aspects, VH1 and VL1 are class II antigen binding sites. In some aspects, VH2 and VL2 are class I antigen binding sites. In some aspects, VH3 and VL3 are class I antigen binding sites. In some aspects, VH4 and VL4 are class III antigen binding sites. In some aspects, VH1 and VL1 are class II antigen binding sites, VH2 and VL2 are class I antigen binding sites, VH3 and VL3 are class I antigen binding sites, and VH4 and VL4 are class III antigen binding sites.

[0098] As used herein, the term "spike protein" refers to the largest of the four major structural proteins found in the SARS-CoV-2 virus. The spike protein assembles into trimers that form large structures, called spikes or peplomers, that project from the surface of the SARS-CoV-2 virion and mediate entry of the virion into host cells. The SARS-CoV-2 spike protein is also called "spike (S) glycoprotein" and "E2." The structural and functional properties of this protein have been characterized. See, e.g., Huang et al., Acta Pharmacol. Sin. 41 : 1141-1149, 2020; Wu et al., Nature 579(7798):265-269, 2020; and Gene ID: 43740568.

[0099] Antigen binding sequences (e.g., CDR, VH, VL, heavy chain and light chain sequences from antibodies) for anti-SARS-CoV-2 proteins are known and described, for example, in U.S. Appl. No. 63 / 147,419. Such sequences include, but are not limited to, SEQ ID NOs: l-40, 81-186 and 188-360.

[0100] As used herein, the term "antigen binding polypeptide" refers to a polypeptide having the ability to specifically bind to one or more substances that induce an immune response (i.e., one or more antigens or epitopes of a SARS-CoV-2 protein).

[0101] As used herein, the term "antigen binding polypeptide complex" refers to a group of four associated polypeptides having the ability to specifically bind to one or more substances that induce an immune response (e.g., one or more antigens or epitopes of a SARS-CoV-2 protein). An antigen binding polypeptide complex, includes, but is not limited to, an antibody or antigen binding fragment thereof.

[0102] The term "antibody" includes, without limitation, a glycoprotein immunoglobulin which binds specifically to an antigen and comprises at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each H chain comprises a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region comprises three constant domains, CHI, CH2 and CH3.Each light chain comprises a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region comprises one constant domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL comprises three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. A heavy chain may have the C-terminal lysine or not. Unless specified otherwise herein, the amino acids in the variable regions are numbered using the Kabat numbering system and those in the constant regions are numbered using the EU system.

[0103] The term "monoclonal antibody," as used herein, refers to an antibody that is produced by a single clone of B-cells and binds to the same epitope. In contrast, the term "polyclonal antibody" refers to a population of antibodies that are produced by different B-cells and bind to different epitopes of the same antigen. The term "antibody" includes, by way of example, monoclonal and polyclonal antibodies; chimeric and humanized antibodies; human or non-human antibodies; wholly synthetic antibodies; and singlechain antibodies. A non-human antibody can be humanized by recombinant methods to reduce its immunogenicity in man.

[0104] The antibody can be an antibody that has been altered (e.g., by mutation, deletion, substitution, conjugation to a non-antibody moiety). For example, an antibody can include one or more variant amino acids (compared to a naturally occurring antibody) which change a property (e.g., a functional property) of the antibody. For example, several such alterations are known in the art which affect, e.g., half-life, effector function, and / or immune responses to the antibody in a patient. The term antibody also includes artificial polypeptide constructs which comprise at least one antibody-derived antigen binding site.

[0105] An "antigen binding fragment" of an antibody refers to one or more fragments or portions of an antibody that retain the ability to bind specifically to the antigen bound by the whole antibody. It has been shown that the antigen binding function of an antibody can be performed by fragments or portions of a full-length antibody. An antigen binding fragment can contain the antigenic determining regions of an intact antibody (e.g., the complementarity determining regions (CDRs)). Examples of antigen binding fragments of antibodies include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single chain antibodies. An antigen binding fragment of an antibody can be derived from any animal species, such as rodents (e.g., mouse, rat, or hamster) and humans or can be artificially produced.

[0106] Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see, e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single chain antibodies are also intended to be encompassed within the term "antigen -binding fragment" of an antibody.

[0107] Antigen binding fragments are obtained using conventional techniques known to those with skill in the art, and the fragments screened for utility in the same manner as are intact antibodies. Antigen binding fragments can be produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins.

[0108] As used herein, the term "variable region" typically refers to a portion of an antibody, generally, a portion of a light or heavy chain, typically about the amino-terminal 110 to 120 amino acids, or 110 to 125 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ extensively in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of an antibody with antigen. In some aspects, the variable region is a mammalian variable region, e.g., a human, mouse or rabbit variable region. In some aspects, the variable region comprises rodent or murine CDRs and human framework regions (FRs). In some aspects, the variable region is a primate (e.g., non-human primate) variable region. In some aspects, the variable region comprises rodent or murine CDRs and primate (e.g., non-human primate) framework regions (FRs).

[0109] The terms "complementarity determining region" or "CDR", as used herein, refer to each of the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops (hypervariable loops) and / or contain the antigen-contacting residues. Antibodies can comprise six CDRs, e.g., three in the VH and three in the VL.

[0110] The terms "VL", "VL region," and "VL domain" are used herein interchangeably to refer to the light chain variable region of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof. In some aspects, a VL region is referred to herein as VL1 to denote a first light chain variable region, VL2 to denote a second light chain variable region, VL3 to denote a third light chain variable region, and VL4 to denote a fourth light chain variable region. An enumerated VL region (e.g., VL1) can have the same or different antigen binding properties and / or the same or different sequence as another enumerated VL region (e.g., VL2).[OHl] The terms "VH", "VH region," and "VH domain" are used herein interchangeably to refer to the heavy chain variable region of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof. In some aspects, a VH region is referred to herein as VH1 to denote a first heavy chain variable region, VH2 to denote a second heavy chain variable region, and VH3 to denote a thirdheavy chain variable region. An enumerated VH region (e.g., VH1) can have the same or different antigen binding properties and / or the same or different sequence as another enumerated VH region (e.g., VH2).

[0112] As used herein, "Kabat numbering" and like terms are recognized in the art and refer to a system of numbering amino acid residues in the heavy and light chain variable regions of an antibody or antigen binding fragment thereof. In some aspects, CDRs can be determined according to the Kabat numbering system (see, e.g., Kabat EA & Wu TT (1971) Ann NY Acad Sci 190: 382-391 and Kabat EA et al., (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). Using the Kabat numbering system, CDRs within an antibody heavy chain molecule are typically present at amino acid positions 31 to 35, which optionally can include one or two additional amino acids, following 35 (referred to in the Kabat numbering scheme as 35 A and 35B) (CDR1), amino acid positions 50 to 65 (CDR2), and amino acid positions 95 to 102 (CDR3). Using the Kabat numbering system, CDRs within an antibody light chain molecule are typically present at amino acid positions 24 to 34 (CDR1), amino acid positions 50 to 56 (CDR2), and amino acid positions 89 to 97 (CDR3).

[0113] As used herein, the terms "constant region" or "constant domain" are used interchangeably to refer to a portion of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof, e.g., a carboxyl terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc region. The constant region generally has a more conserved amino acid sequence relative to a variable region. In some aspects, an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof comprises a constant region or portion thereof that is sufficient for antibody- dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). A constant region includes, but is not limited to, a light chain constant region (CL) or heavy chain constant region (CHI, CH2, CH3).

[0114] As used herein, the terms "fragment crystallizable region," "Fc region," or "Fc domain" are used interchangeably herein to refer to the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of thecomplement system. Fc regions typically comprise CH2 and CH3 regions, and, optionally, an immunoglobulin hinge.

[0115] As used herein, the terms "immunoglobulin hinge," "hinge," "hinge domain" or "hinge region" are used interchangeably to refer to a stretch of heavy chains between the Fab and Fc portions of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof. A hinge provides structure, position and flexibility, which assist with normal functioning of antibodies (e.g., for crosslinking two antigens or binding two antigenic determinants on the same antigen molecule). An immunoglobulin hinge is divided into upper, middle and lower hinge regions that can be separated based on structural and / or genetic components. An immunoglobulin hinge of the invention can contain one, two or all three of these regions. Structurally, the upper hinge region stretches from the C terminal end of CHI to the first hinge disulfide bond. The middle hinge region stretches from the first cysteine to the last cysteine in the hinge. The lower hinge region extends from the last cysteine to the glycine of CH2. The cysteines present in the hinge form interchain disulfide bonds that link the immunoglobulin monomers.

[0116] As used herein, the term "Fab" refers to a region of an antibody that binds to an antigen. It is typically composed of one constant and one variable domain of each of the heavy and the light chain.

[0117] As used herein, the term "heavy chain" refers to a portion of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof typically composed of a heavy chain variable region (VH), a heavy chain constant region 1 (CHI), a heavy chain constant region 2 (CH2), and a heavy chain constant region 3 (CH3). A typical antibody is composed of two heavy chains and two light chains. When used in reference to an antibody, a heavy chain can refer to any distinct type, e.g., alpha (a), delta (5), epsilon (a), gamma (y), and mu (p), based on the amino acid sequence of the constant region, which gives rise to IgA, IgD, IgE, IgG, and IgM classes of antibodies, respectively, including subclasses of IgG, e.g., IgGl, IgG2, IgG3, and IgG4. Heavy chain amino acid sequences are known in the art. In some aspects, the heavy chain is a human heavy chain.

[0118] As used herein, the term "light chain" refers to a portion of an antigen binding polypeptide, antigen binding polypeptide complex, antibody or antigen binding fragment thereof typically composed of a light chain variable region (VL) and a light chainconstant region (CL). A typical antibody is composed of two light chains and two heavy chains. When used in reference to an antibody, a light chain can refer to any distinct type, e.g., kappa (K) or lambda (X), based on the amino acid sequence of the constant region. Light chain amino acid sequences are known in the art. In some aspects, the light chain is a human light chain.

[0119] The term "chimeric" antibody or antigen binding fragment thereof refers to an antibody or antigen binding fragments thereof wherein the amino acid sequence is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen binding fragments thereof derived from one species of mammals (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity and capability, while the constant regions are homologous to the sequences in antibodies or antigen binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species.

[0120] The term "humanized" antibody or antigen binding fragment thereof refers to forms of non-human (e.g., murine) antibodies or antigen binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies or antigen binding fragments thereof are human immunoglobulins in which residues from a complementary determining region (CDR) are replaced by residues from a CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability (Jones et al., Nature 321 :522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239: 1534-1536 (1988)). In some aspects, the Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody or fragment from a non-human species that has the desired specificity, affinity, and capability. The humanized antibody or antigen binding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and / or within the replaced non-human residues to refine and optimize antibody or antigen-binding fragment thereof specificity, affinity, and / or capability. In general, a humanized antibody or antigen binding fragment thereof will comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. A humanized antibody or antigen bindingfragment thereof can also comprise at least a portion of a constant region, typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are known and described, for example, in U.S. Pat. No. 5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-973 (1994), and Roguska et al., Protein Eng. 9(10) : 895- 904 (1996).

[0121] The term "human" antibody or antigen binding fragment thereof, as used herein, means an antibody or antigen binding fragment thereof having an amino acid sequence derived from a human immunoglobulin gene locus, where such antibody or antigen binding fragment is made using recombinant techniques known in the art. This definition of a human antibody or antigen binding fragment thereof includes intact or full-length antibodies and fragments thereof.

[0122] A polypeptide, polypeptide complex, antibody, antigen binding fragment thereof, polynucleotide, vector or host cell which is "isolated" is a polypeptide, polypeptide complex, antibody, antigen binding fragment thereof, polynucleotide, vector or host cell which is in a form not found in nature. Isolated polypeptides, polypeptide complexes, antibodies, antigen binding fragments thereof, polynucleotides, vectors or host cells include those which have been purified to a degree that they are no longer in a form in which they are found in nature. In some aspects, a polypeptide, polypeptide complex, antibody, antigen binding fragment thereof, polynucleotide, vector or host cell which is isolated is substantially pure. As used herein, "substantially pure" refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[0123] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. It is understood that, because the polypeptides of this invention are based upon antibodies, in some aspects, the polypeptides can occur as single chains or associated chains.

[0124] As used herein, an "isoelectric point" or "pl" refer to the pH at which the net charge of a polypeptide (e.g., an antigen binding polypeptide or antigen binding polypeptide complex provided herein) is zero.

[0125] As used herein, "pH" refers to a quantitative measure of acidity or basicity. This term translates the values of the concentration of the hydrogen ion — which ordinarily ranges between about 1 and IO-14gram-equivalents per litre — into numbers between 0 and 14.

[0126] As used herein, "SARS-CoV-2 escape" refers to the process by which a SARS- CoV-2 virus acquires one or more mutations that allow the virus to evade the antibodies generated by a particular vaccine.

[0127] As used herein, "SARS-CoV-2 evolution" refers to the heritable genetic changes that a SARS-CoV-2 virus accumulates during its life time, which can arise from adaptations in response to environmental changes or the immune response of the host.

[0128] The use of the alternative (e.g., "or") should be understood to mean either one, both, or a combination thereof of the alternatives. As used herein, the indefinite articles "a" or "an" should be understood to refer to "one or more" of any recited or enumerated component.

[0129] As used herein, the term "and / or" is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0130] It is understood that wherever aspects are described herein with the language "comprising," "having," or the like, otherwise analogous aspects described in terms of "consisting of' and / or "consisting essentially of are also provided.

[0131] As used herein, the term "about" refers to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation per the practice in the art. Alternatively, "about" can mean a range of up to 10% or 20% (i.e., ±10% or ±20%). Forexample, about 3 mg can include any number between 2.7 mg and 3.3 mg (for 10%) or between 2.4 mg and 3.6 mg (for 20%). Furthermore, particularly with respect to biological systems or processes, the terms can mean up to an order of magnitude or up to 5-fold of a value. When particular values or compositions are provided in the application and claims, unless otherwise stated, the meaning of "about" should be assumed to be within an acceptable error range for that particular value or composition.

[0132] As described herein, any numerical range, concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one-tenth and one- hundredth of an integer), unless otherwise indicated.

[0133] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 5th ed., 2013, Academic Press; and the Oxford Dictionary Of Biochemistry And Molecular Biology, 2006, Oxford University Press, provide one of skill with a general dictionary of many of the terms used in this disclosure.

[0134] Units, prefixes, and symbols are denoted in their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure, which can be had by reference to the specification as a whole. Accordingly, the terms defined herein are more fully defined by reference to the specification in its entirety.

[0135] Various aspects are described in further detail in the following sections.Antigen Binding Polypeptides and Polypeptide Complexes

[0136] Provided herein are antigen binding polypeptides and polypeptide complexes having certain structural features. These features include a cross-over dual variable (CODV) structure, which has been described, for example, in Int'l Pub. No. WO2017180913 A2.

[0137] In some aspects, an antigen binding polypeptide complex provided herein comprises a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by VL1-L1-CL; wherein the second polypeptide has a structure represented by VH1-L2-CH1; wherein thethird polypeptide has a structure represented by VH2-L3-VH3-L4-CH1; wherein the fourth polypeptide has a structure represented by VL3-L5-VL2-L6-CL; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS- CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; CHI is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-L6 are amino acid linkers.

[0138] In some aspects, an antigen binding polypeptide complex provided herein comprises a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by VL1-L1-CL; wherein the second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; wherein the third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6- Fc; wherein the fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally, an immunoglobulin hinge; CHI is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-L8 are amino acid linkers.

[0139] In some aspects, VH1 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345). In some aspects, VL1 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH1 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148- 150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225- 227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297- 299, 319-321, 327-329, 335-337 and 343-345), and VL1 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172- 174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253- 255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH2 comprises different CDR1, CDR2 and / or CDR3 sequences than VH1 and VH3 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345), and / or VL2 comprises different CDR1, CDR2 and / or CDR3 sequences than VL1 and VL3 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0140] In some aspects, VH1 and VH2 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345). In some aspects, VL1 and VL2 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH1 and VH2 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148- 150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225- 227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297- 299, 319-321, 327-329, 335-337 and 343-345), and VL1 and VL2 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172- 174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253- 255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH3 comprises different CDR1, CDR2 and / or CDR3 sequences than VH1 and VH2 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345), and / or VL3 comprises different CDR1, CDR2 and / or CDR3 sequences than VL1 and VL2 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0141] In some aspects, VH2 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345). In some aspects, VL2 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences(e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH2 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148- 150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225- 227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297- 299, 319-321, 327-329, 335-337 and 343-345), and VL2 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172- 174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253- 255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH1 comprises different CDR1, CDR2 and / or CDR3 sequences than VH2 and VH3 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345), and / or VL1 comprises different CDR1, CDR2 and / or CDR3 sequences than VL2 and VL3 (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some preferred aspects,CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0142] In some aspects, VH1, VH2 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345). In some aspects, VL1, VL2 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH1, VH2 and VH3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217- 219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289- 291, 297-299, 319-321, 327-329, 335-337 and 343-345), and VL1, VL2 and VL3 each comprise the same CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325,331-333, 339-341 and 347-349). In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0143] In some aspects, VH1, VH2 and VH3 each comprise different CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 319-321, 327-329, 335-337 and 343-345). In some aspects, VL1, VL2 and VL3 each comprise different CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239, 245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some aspects, VH1, VH2 and VH3 each comprise different CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2-4, 10-12, 18-20, 26-28, 34-36, 148-150, 160-162, 168-170, 176-178, 184-186, 193-195, 201-203, 209-211, 217- 219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289- 291, 297-299, 319-321, 327-329, 335-337 and 343-345), and VL1, VL2 and VL3 each comprise different CDR1, CDR2 and / or CDR3 sequences (e.g., an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: 6-8, 14-16, 22-24, 30-32, 38-40, 152-154, 156-158, 164-166, 172-174, 180-182, 197-199, 205-207, 213-215, 221-223, 229-231, 237-239,245-247, 253-255, 261-263, 269-271, 277-279, 285-287, 293-295, 301-303, 323-325, 331-333, 339-341 and 347-349). In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with the corresponding amino acid sequences specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0144] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241, 249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; and / or a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243, 251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0145] In some aspects, VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence of LGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); and / or a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0146] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18,26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241, 249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; and / or a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243, 251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence of LGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); and / or a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100%identity to any one of SEQ ID N0s:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0147] In some aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20. In some preferred aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20.

[0148] In some aspects, VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100%identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24. In some preferred aspects, VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1, VL2 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0149] In some aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NOs:20; and VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24. In some preferred aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18;a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VL1, VL2 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0150] In some aspects, VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; and VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28. In some preferred aspects, VH1 and VH3 each comprise a CDR1 comprising an amino acidsequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0151] In some aspects, VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferredaspects, VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0152] In some aspects, VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; aCDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VL1 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0153] In some aspects, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28. In some preferred aspects, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH2 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0154] In some aspects, VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 and VL2 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0155] In some aspects, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having atleast 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH2 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VL1 and VL2 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0156] In some aspects, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; and VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28. In some preferred aspects, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH2 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0157] In some aspects, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL2 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0158] In some aspects, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identityto SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an aminoacid sequence having at least 90% identity to SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH2 and VH3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VL2 and VL3 each comprise a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0159] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VH3 comprises a CDR1 comprising theamino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28.

[0160] In some aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprisingan amino acid sequence having at least 90% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0161] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQID NO: 10; a CDR2 comprising the amino acid of SEQ ID NO:11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32.

[0162] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; and VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20.

[0163] In some aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, atleast 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24. In some preferred aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acidsequence having at least 90% identity to SEQ ID NO:32; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0164] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least99% or 100% identity to SEQ ID NO:28; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 91%, at least 92%, at least 93%, at least 94%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising theamino acid sequence of SEQ ID NO:28; VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0165] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20.

[0166] In some aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQID N0:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24. In some preferred aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having atleast 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0167] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQID NO:24. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the aminoacid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24.

[0168] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12. In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; and VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; and VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12.

[0169] In some aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an aminoacid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16. In some preferred aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the aminoacid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0170] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 12; VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 16. . In some preferred aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:28; VH2comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 12; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO:24; and VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 16. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:26; a CDR2 comprising the amino acid sequence of SEQ ID NO:27; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28; VH2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 18; a CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:20; VH3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO:11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; VL1 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:30; a CDR2 comprising the amino acid sequence of SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; VL2 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:22; a CDR2 comprising the amino acid sequence of SEQ ID NO:23 (having the sequence of GAS); and a CDR3comprising the amino acid sequence of SEQ ID NO:24; and VL3 comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a CDR2 comprising the amino acid sequence of SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0171] In some aspects, VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 148. In some aspects, VH1 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 149. In some aspects, VH1 comprises a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 150. In some aspects, VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 148. In some aspects, VH2 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 149. In some aspects, VH2 comprises a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 150. In some aspects, VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 148. In some aspects, VH3 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 149. In some aspects, VH3 comprises a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100%identity to SEQ ID NO: 150. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, and VH3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects CDR1, CDR2 and CDR3 of each of VH1, VH2, and VH3 comprise or consist of a corresponding amino acid sequence specified above.

[0172] In some aspects, VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 152. In some aspects, VL1 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 153. In some aspects, VL1 comprises a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 154. In some aspects, VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 152. In some aspects, VL2 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 153. In some aspects, VL2 comprises a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 154. In some aspects, VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 152. In some aspects, VL3 comprises a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 153. In some aspects, VL3 comprises a CDR3comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 154. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0173] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 193; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 194; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 195; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 197; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 198 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 199. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100%identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0174] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:201; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:202; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:203; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:205; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:206 (having the sequence of DVS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:207. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0175] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%,at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:209; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:210; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:211; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:213; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:214 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:215. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0176] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:217; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:218; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:219; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:221; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:222 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:223. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0177] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:225; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:226; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:227; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:229; a CDR2 comprising an amino acid sequencehaving at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:230 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:231. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0178] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:233; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:234; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:235; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:237; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:238 (having the sequence of AAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:239. In some preferred aspects, CDR1, CDR2and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0179] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:241; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:242; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:243; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:245; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:246 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:247. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0180] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:249; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:250; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:251; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:253; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:254 (having the sequence of DDS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:255. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0181] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:257; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, atleast 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:258; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:259; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:261; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:262 (having the sequence of KDS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:263. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0182] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:265; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:266; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:267; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an aminoacid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:269; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:270 (having the sequence of SAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:271. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0183] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:273; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:274; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:275; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:277; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:278 (having the sequence of SAS); and a CDR3 comprising anamino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:279. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0184] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:281; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:282; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:283; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:285; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:286 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:287. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100%identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0185] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:289; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:290; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:291; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:293; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:294 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:295. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0186] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%,at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:297; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:298; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:299; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:301; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:302 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:303. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0187] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:319; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:320; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:321; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:323; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:324 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:325. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0188] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:327; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:328; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:329; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:331; a CDR2 comprising an amino acid sequencehaving at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:332 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:333. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0189] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:335; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:336; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:337; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:339; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:340 (having the sequence of SAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:341. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90%identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0190] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:343; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:344; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:345; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:347; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:348 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:349. In some preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, CDR1, CDR2 and CDR3 of each of VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0191] In some aspects, VH1 comprises the same heavy chain variable region as VH3. In some aspects, VL1 comprises the same light chain variable region as VL3. In someaspects, VH1 comprises the same heavy chain variable region as VH3, and VL1 comprises the same light chain variable region as VL3.

[0192] In some aspects, VH1 comprises the same heavy chain variable region as VH2. In some aspects, VL1 comprises the same light chain variable region as VL2. In some aspects, VH1 comprises the same heavy chain variable region as VH2, and VL1 comprises the same light chain variable region as VL2.

[0193] In some aspects, VH2 comprises the same heavy chain variable region as VH3. In some aspects, VL2 comprises the same light chain variable region as VL3. In some aspects, VH2 comprises the same heavy chain variable region as VH3, and VL2 comprises the same light chain variable region as VL3.

[0194] In some aspects, VH1, VH2 and VH3 each comprise the same heavy chain variable region. In some aspects, VL1, VL2 and VL3 each comprise the same light chain variable region. In some aspects, VH1, VH2 and VH3 each comprise the same heavy chain variable region, and VL1, VL2 and VL3 each comprise the same light chain variable region.

[0195] In some aspects, VH1, VH2 and VH3 each comprise different heavy chain variable regions. In some aspects, VL1, VL2 and VL3 each comprise different light chain variable regions. In some aspects, VH1, VH2 and VH3 each comprise different heavy chain variable regions, and VL1, VL2 and VL3 each comprise different light chain variable regions. In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359. In some preferred aspects, VH1, VH2, and VH3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, and VH3 comprise or consist of a corresponding amino acid sequence specified above. In some aspects, VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL I and VL2; VL I and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, atleast 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346. In some preferred aspects, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above. In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs: l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346. In some aspects, the sequence has a mutation at N62, for example, N62Q or N62Q at, for example, SEQ ID NO: 175. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0196] In some aspects, VH1, VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; and VL1, VL2 and VL3 each comprise an amino acidsequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21. In some preferred aspects, VH1, VH2 and VH3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO: 17; and VL1, VL2 and VL3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO:21. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2 and VH3 each comprise the amino acid sequence of SEQ ID NO: 17; and VL1, VL2 and VL3 each comprise the amino acid sequence of SEQ ID NO:21.

[0197] In some aspects, VH1 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21; and VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29. In some preferred aspects, VH1 and VH3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VH2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VL1 and VL3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO:21; and VL2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH3 each comprise the amino acid sequence of SEQ ID NO: 17; VH2 comprises the amino acid sequence of SEQ ID NO:25; VL1 and VL3 each comprise the amino acid sequence of SEQ ID NO:21; and VL2 comprises the amino acid sequence of SEQ ID NO:29.

[0198] In some aspects, VH1 and VH2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29. In some preferred aspects, VH1 and VH2 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VL1 and VL2 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 and VH2 each comprise the amino acid sequence of SEQ ID NO: 17; VH3 comprises the amino acid sequence of SEQ ID NO:25; VL1 and VL2 each comprise the amino acid sequence of SEQ ID NO:21; and VL3 comprises the amino acid sequence of SEQ ID NO:29.

[0199] In some aspects, VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VL2 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21; and VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29. In some preferred aspects, VH2 and VH3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VH1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VL2 and VL3 each comprise an amino acid sequence having at least 90% identity to SEQ ID NO:21; and VL1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH2 and VH3 each comprise the amino acid sequence of SEQ ID NO: 17; VH1 comprises the amino acid sequence of SEQ ID NO:25; VL2 and VL3 each comprise the amino acid sequence of SEQ ID NO:21; and VL1 comprises the amino acid sequence of SEQ ID NO:29.

[0200] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29. In some preferred aspects, VH1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VL1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least90% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises the amino acid sequence of SEQ ID NO:9; VH2 comprises the amino acid sequence of SEQ ID NO: 17; VH3 comprises the amino acid sequence of SEQ ID NO:25; VL1 comprises the amino acid sequence of SEQ ID NO: 13; VL2 comprises the amino acid sequence of SEQ ID NO:21; and VL3 comprises the amino acid sequence of SEQ ID NO:29.

[0201] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21. In some preferred aspects, VH1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VH3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29; and VL3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:21. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recitedreference sequence. In some particularly preferred aspects, VH1 comprises the amino acid sequence of SEQ ID NO:9; VH2 comprises the amino acid sequence of SEQ ID NO:25; VH3 comprises the amino acid sequence of SEQ ID NO: 17; VL1 comprises the amino acid sequence of SEQ ID NO: 13; VL2 comprises the amino acid sequence of SEQ ID NO:29; and VL3 comprises the amino acid sequence of SEQ ID NO:21.

[0202] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:9; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 13; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21. In some preferred aspects, VH1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:9; VH3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 13; and VL3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:21. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises the amino acid sequence of SEQ ID NO:25; VH2 comprises the amino acid sequence of SEQ ID NO:9; VH3 comprises the amino acid sequence of SEQ ID NO: 17; VL1 comprises theamino acid sequence of SEQ ID NO:29; VL2 comprises the amino acid sequence of SEQ ID NO: 13; and VL3 comprises the amino acid sequence of SEQ ID NO:21.

[0203] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:9; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 13. In some preferred aspects, VH1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 90 identity to SEQ ID NO:17; VH3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:9; VL1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 13. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1 comprises the amino acid sequence of SEQ ID NO:25; VH2 comprises the amino acid sequence of SEQ ID NO: 17; VH3 comprises the amino acid sequence of SEQ ID NO:9; VL1 comprises the amino acid sequence of SEQ ID NO:29; VL2 comprises the amino acid sequence of SEQ ID NO:21; and VL3 comprises the amino acid sequence of SEQ ID NO: 13.

[0204] In some aspects, VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 147. In some aspects, VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 147. In some aspects, VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 147. In some aspects, VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 151. In some aspects, VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 151. In some aspects, VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 151. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0205] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 192; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 196. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0206] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:200; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:204. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0207] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:208; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:212. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0208] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence havingat least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:216; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:220. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with the corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0209] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:224; and VL1, VL2 and / or VL3 comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:228. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with the corresponding amino acid sequences specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0210] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:232; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity- I l l - to SEQ ID NO:236. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0211] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:240; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:244. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% and 100% identity to the recited reference sequence. In some particularly preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of a corresponding amino acid sequence specified above.

[0212] In some aspects, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:248; and VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:252. In some preferred aspects, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity with a corresponding amino acid sequence specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%, 96%, 9...

Claims

WHAT IS CLAIMED IS:

1. An antigen binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by:VL1-L1-CL; wherein the second polypeptide has a structure represented by:VH1-L2-CH1; wherein the third polypeptide has a structure represented by:VH2-L3-VH3-L4-CH1; wherein the fourth polypeptide has a structure represented by:VL3-L5-VL2-L6-CL; wherein:VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS- CoV-2 protein;VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein;VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;CHI is an immunoglobulin heavy chain constant region 1;CL is an immunoglobulin light chain constant region; andL1-L6 are amino acid linkers.

2. An antigen binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; wherein the first polypeptide has a structure represented by:VL1-L1-CL; wherein the second polypeptide has a structure represented by:VH1-L2-CH1-L3-Fc; wherein the third polypeptide has a structure represented by:VH2-L4- VH3 -L5 -CH 1 -L6-Fc; wherein the fourth polypeptide has a structure represented by:VL3-L7-VL2-L8-CL; wherein:VL1 is a first immunoglobulin light chain variable region that specifically binds to a SARS- CoV-2 protein;VL2 is a second immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein;VL3 is a third immunoglobulin light chain variable region that specifically binds to a SARS-CoV-2 protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;VH2 is a second immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;VH3 is a third immunoglobulin heavy chain variable region that specifically binds to a SARS-CoV-2 protein;Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally, an immunoglobulin hinge;CHI is an immunoglobulin heavy chain constant region 1;CL is an immunoglobulin light chain constant region; andL1-L8 are amino acid linkers.

3. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises the same heavy chain variable region as VH3, and VL1 comprises the same light chain variable region as VL3.

4. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises the same heavy chain variable region as VH2, and VL1 comprises the same light chain variable region as VL2.

5. The antigen binding polypeptide complex of claim 1 or 2, wherein VH2 comprises the same heavy chain variable region as VH3, and VL2 comprises the same light chain variable region as VL3.

6. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1, VH2 and VH3 each comprise the same heavy chain variable region, and VL1, VL2 and VL3 each comprise the same light chain variable region.

7. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1, VH2 and VH3 each comprise different heavy chain variable regions, and VL1, VL2 and VL3 each comprise different light chain variable regions.

8. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1, VH2 and VH3 each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241, 249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242, 250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243, 251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; and wherein VL1, VL2 and VL3 each independently comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence of LGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having thesequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349.

9. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; and wherein VL1, VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

10. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; aCDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and wherein VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

11. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and wherein VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

12. The antigen binding polypeptide complex of claim 1 or 2, wherein VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and wherein VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and aCDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

13. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; wherein VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; wherein VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and aCDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and wherein VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32.

14. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; wherein VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and aCDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; wherein VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; and wherein VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

15. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; wherein VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an aminoacid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; wherein VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16; and wherein VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24.

16. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:26; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:27; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 28; wherein VH2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 19; and a CDR3 comprising an aminoacid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:20; wherein VH3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 12; wherein VL1 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:30; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:32; wherein VL2 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:22; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:24; and wherein VL3 comprises a CDR1 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 16.

17. The antigen binding polypeptide complex of claim 1 or 2, wherein VH1, VH2 and VH3 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs: 1, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359.

18. The antigen binding polypeptide complex of claim 17, wherein VL1, VL2 and VL3 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346.

19. The antigen binding polypeptide complex of claim 17, wherein VH1, VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; and VL1, VL2 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

20. The antigen binding polypeptide complex of claim 17, wherein VH1 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

21. The antigen binding polypeptide complex of claim 17, wherein VH1 and VH2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 and VL2 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

22. The antigen binding polypeptide complex of claim 17, wherein VH2 and VH3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity toSEQ ID NO:25; VL2 and VL3 each comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

23. The antigen binding polypeptide complex of claim 17, wherein VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29.

24. The antigen binding polypeptide complex of claim 17, wherein VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

25. The antigen binding polypeptide complex of claim 17, wherein VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%,at least 99% or 100% identity to SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21.

26. The antigen binding polypeptide complex of claim 17, wherein VH1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:25; VH2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:9; VL1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:29; VL2 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO:21; and VL3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to SEQ ID NO: 13.

27. The antigen binding polypeptide complex of any one of claims 1-26, wherein the immunoglobulin hinge comprises an upper hinge region, a middle hinge region, a lower hinge region, or a combination thereof.

28. The antigen binding polypeptide complex of any one of claims 1-27, wherein linkers L1-L8 each independently have a length of from about 0 amino acids to about 50 amino acids.

29. The antigen binding polypeptide complex of any one of claims 1-28, wherein linkers L1-L8 each independently comprise an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:46-80 (wherein SEQ ID NO:47 has the sequence of G, SEQ ID NO:48 has the sequence of A, SEQ ID NO:49 has the sequence of GSS, and SEQ ID NO:50 has the sequence of ASG).

30. The antigen binding polypeptide complex of any one of claims 1-29, wherein one or more of linkers L1-L8 are non-immunogenic.

31. The antigen binding polypeptide complex of any one of claims 1-30, wherein one or more of linkers L1-L8 do not contain a consensus T cell epitope.

32. The antigen binding polypeptide complex of any one of claims 1-31, wherein the Fc region comprises at least one knob-into-hole modification or Fc effector function knockout mutation.

33. The antigen binding polypeptide complex of claim 32, wherein the antigen binding polypeptide complex is an IgGl or IgG4 antibody and the knob-into-hole modification comprises:(i) knob substitutions of S354C and T366W and hole substitutions of Y349C, T366S, L368A and Y407V;(ii) hole substitutions of M428L and N434S or N434A;(iii) hole substitutions of M252Y, S254T and T256E; or(iv) a combination thereof; based on the EU numbering scheme.

34. The antigen binding polypeptide complex of claim 32, wherein the antigen binding polypeptide complex is an IgGl or IgG4 antibody and the Fc effector function knockout mutation is L234A, L235A, P239A or a combination thereof, based on the EU numbering scheme.

35. The antigen binding polypeptide complex of any one of claims 1-34 comprising a detectable label.

36. The antigen binding polypeptide complex of claim 35, wherein the detectable label is a radioactive label, chemiluminescent label, fluorescent label, enzyme, peptide tag, or a combination thereof.

37. The antigen binding polypeptide complex of claim 36, wherein the peptide tag is a polyhistidine tag consisting of from about four to about 10 histidine residues.

38. The antigen binding polypeptide complex of claim 37, wherein the polyhistidine tag consists of about eight histidine residues.

39. The antigen binding polypeptide complex of any one of claims 1-38 that specifically binds to a SARS-CoV-2 protein with an equilibrium dissociation constant (KD) of from about 10 pM to about 1 pM.

40. The antigen binding polypeptide complex of any one of claims 1-39, wherein the SARS-CoV-2 virus is the original Wuhan strain (WAI), D614G spike protein mutant (D614G), Alpha variant (B.1.1.7), Beta variant 1 (B.1.351.vl), Gamma variant (P.1), Delta variant(B.1.617.2 or AY. l), Kappa variant (B.1.617.1), Iota variant (B.1.526), Lambda variant (C.37), Mu variant (B.1.621), C.1.2 variant, Epsilon variant (B.1.427), or Omicron variant (BAI .1.529, BA. l, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ. l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ. l, XBB, XBB1.5, BF.7 or CH.1.1), or a combination thereof.

41. An antibody or antigen binding fragment thereof comprising the antigen binding polypeptide complex of any one of claims 1-40.

42. The antibody or antigen binding fragment thereof of claim 41, wherein the antibody is IgG, IgM, IgE, IgA or IgD.

43. The antibody or antigen binding fragment thereof of claim 42, wherein the IgG is IgGl, IgG2, IgG3 or IgG4.

44. The antibody or antigen binding fragment thereof of claim 41, wherein the antigen binding fragment is a Fab, scFab, Fab', F(ab')2, Fv or scFv.

45. The antibody or antigen binding fragment thereof of any one of claims 41-44, wherein the antibody is human or humanized.

46. The antibody or antigen binding fragment thereof of any one of claims 41-45, wherein the antibody is a monoclonal antibody, grafted antibody, or chimeric antibody.

47. An anti-SARS-CoV2 multivalent antibody that exhibits improved prevention of immune escape compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

48. A pharmaceutical composition comprising the antigen binding polypeptide complex of any one of claims 1-40.

49. A pharmaceutical composition comprising the antigen binding polypeptide complex of any one of claims 1-40 and an additional pharmaceutical agent.

50. A pharmaceutical composition comprising the antigen binding polypeptide complex of any one of claims 1-40 and a pharmaceutically acceptable carrier.

51. A pharmaceutical composition comprising the antigen binding polypeptide complex of any one of claims 1-40, an additional pharmaceutical agent, and a pharmaceutically acceptable carrier.

52. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any one of claims 41-47.

53. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any one of claims 41-47, and an additional pharmaceutical agent.

54. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any one of claims 41-47 and a pharmaceutical acceptable carrier.

55. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any one of claims 41-47, an additional pharmaceutical agent, and a pharmaceutical acceptable carrier.

56. The pharmaceutical composition of any one of claims 49, 51, 53 and 55, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, an agent that potentiates vitamin D action, an anti-viral agent, an anti-malarial agent, an antibiotic, or a combination thereof.

57. The pharmaceutical composition of claim 56, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D.

58. The pharmaceutical composition of claim 56, wherein the agent that potentiates vitamin D action is a CYP24 inhibitor, 1,25-dihydroxyvitamin D compound, or a combination thereof.

59. The pharmaceutical composition of claim 56, wherein the anti-viral agent is an anti-retroviral agent, an antibody against SARS-CoV-2 virus, an inhibitor of reverse transcriptase, or a combination thereof.

60. The pharmaceutical composition of claim 56, wherein the anti-viral agent is maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of aciclovir, ganciclovir, cidofovir, forcarnet, ribavirin, interferon alpha, pegylated interferon alpha, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peremivir, valaciclovir, penciclovir, valganciclovir, foscamet, tenofovir, adefovir, entecavir, lamivudine, telbivudine, ribavirin, glecaprevir, grazoprevir, paritaprevir, simeprevir, voxilaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofobuvir, bebtelovimab, or a combination thereof.

61. The pharmaceutical composition of claim 60, wherein the anti-viral agent is bebtelovimab.

62. The pharmaceutical composition of claim 56, wherein the anti-viral agent is Retrovir® (3 '-azido-3 '-deoxypyrimidine, zidovudine), 3 '-azido-3 '-deoxythymidine (AZT), HMD® (2', 3 '-dideoxy cytidine, zalcitabine), VidexEC® (2', 3 'dideoxyinosine, didanosine), Epivir® (lamivudine), Zerit® (stavudine), Viread® (tenofovir DF), Ziagen® (abacavir), Emtriva® (emtricitabine, FTC), Rescriptor® (delavirdine), Sustiva® (efavirenz), Viramune® (nevirapine, 1 l-cyclopropyl-4-methyl-5,l l-dihydro-6H-dipyrido[3,2-b:2',3'-e][l,4]diazepin-6- one), trisodium phosphonoformate, ammonium-21-tungstenato-9-antimonate, 1-P-D- ribofuranoxyl-1, 2, 4-triazole-3 -carboxamide, Aganerase® (amprenavir), Reyataz® (atazanavir), Lexiva® (fosamprenavir), Crixivan® (indinavir), Viracept® (nelfinavir), Norvir® (ritonavir), Fortovase® or Invirase® (saquinavir), lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy- 6-phenyl-2(R)(2,3,4-trimethoxyphenylmethyl)-hexanoyl-(L)-valyl-N-(2-metoxy-ethyl)-amide), adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011 BS (palinavir), polymannoacetate, Fuzeon® (enfuvirtide, T-20), Epzicom® (abacavir and lamivudine), Trizivir® (abacavir, lamivudine and zidovudine), Truvada® (emtricitabine and tenofir DF), Combivir® (lamivudine and zidovudine), Kaletra® (lopinavir and ritonavir), or a combination thereof.

63. A kit comprising the antigen binding polypeptide complex of any one of claims 1- 40.

64. A kit comprising the antibody or antigen binding fragment thereof of any one of claims 41-47.

65. A kit comprising (i) the antigen binding polypeptide complex of any one of claims 1-40 or the antibody or antigen binding fragment thereof of any one of claims 41-47, and (ii) an additional pharmaceutical agent.

66. A kit comprising the pharmaceutical composition of any one of claims 48-62.

67. A kit comprising (i) the pharmaceutical composition of any one of claims 48-62, and (ii) an additional pharmaceutical agent.

68. A kit comprising (i) the pharmaceutical composition of any one of claims 48-62, and (ii) a pharmaceutical composition comprising an additional pharmaceutical agent.

69. A kit comprising (i) the pharmaceutical composition of any one of claims 48-62, and (ii) a pharmaceutical composition comprising an additional pharmaceutical agent and a pharmaceutically acceptable carrier.

70. The kit of any one of claims 63-69, further comprising instructions for use.

71. A method of preventing or treating a SARS-CoV-2 viral infection in a subject in need thereof, comprising administering to the subject an effective amount of the antigen binding polypeptide complex of any one of claims 1-40, the antibody or antigen binding fragment thereof of any one of claims 41-47, the pharmaceutical composition of any one of claims 48-62, or a combination thereof.

72. A method of preventing or treating coronavirus disease 2019 (COVID-19) in a subject in need thereof, comprising administering to the subject an effective amount of the antigen binding polypeptide complex of any one of claims 1-40, the antibody or antigen binding fragment thereof of any one of claims 41-47, the pharmaceutical composition of any one of claims 48-62, or a combination thereof.

73. A method of diagnosing a subject as being infected with a SARS-CoV-2 virus or suspected of being infected with a SARS-CoV-2 virus, comprising (i) contacting a sample obtained from the subject with the antigen binding polypeptide complex of any one of claims 1- 40 or the antibody or antigen binding fragment thereof of any one of claims 41-47; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as being infected with a SARS-CoV-2 virus or suspected of being infected with a SARS-CoV-2 virus when the presence of the virus complex is detected.

74. A method of diagnosing a subject as not being infected with a SARS-CoV-2 virus or not suspected of being infected with a SARS-CoV-2 virus, comprising (i) contacting a sample obtained from the subject with the antigen binding polypeptide complex of any one of claims 1- 40 or the antibody or antigen binding fragment thereof of any one of claims 41-47; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as not being infected with a SARS-CoV-2 virus or not suspected of being infected with a SARS- CoV-2 virus when the presence of the virus complex is not detected.

75. A method of diagnosing a subject as having COVID-19 or suspected of having COVID-19, comprising (i) contacting a sample obtained from the subject with the antigen binding polypeptide complex of any one of claims 1-40 or the antibody or antigen binding fragment thereof of any one of claims 41-47; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as having COVID-19 or suspected of having CO VID-19 when the presence of the virus complex is detected.

76. A method of diagnosing a subject as not having COVID-19 or not suspected of having COVID-19, comprising (i) contacting a sample obtained from the subject with the antigen binding polypeptide complex of any one of claims 1-40 or the antibody or antigen binding fragment thereof of any one of claims 41-47; (ii) detecting the presence or absence of a virus complex which contains the polypeptide complex, antibody or fragment and a SARS-CoV-2 virus, virion or fragment thereof; and (iii) diagnosing the subject as not having COVID-19 or not suspected of having CO VID-19 when the presence of the virus complex is not detected.

77. The method of any one of claims 73-76, wherein the sample is a nasal swab, tissue sample, saliva, plasma or blood.

78. The method of any one of claims 73-77, wherein detecting the presence or absence of the virus complex comprises an enzyme linked immunosorbent assay (ELISA), immunospot assay, lateral flow assay, flow cytometry, immunohistochemistry or western blot.

79. The method of any one of claims 71-78, wherein the SARS-CoV-2 virus is the original Wuhan strain (WAI), D614G spike protein mutant (D614G), Alpha variant (B.1.1.7), Beta variant 1 (B.1.351.vl), Gamma variant (P. l), Kappa variant (B.1.617.1), Delta variant (B.1.617.2 or AY.1), Epsilon variant (B.1.427), Iota variant (B.1.526), Lambda variant (C.37), Mu variant (B.1.621), C.1.2 variant, Omicron variant (BAL 1.529, BA.l, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.l, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

80. A method of preventing immune escape of a SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an anti-SARS-CoV2 multivalent antibody that exhibits improved prevention of immune escape compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

81. A method of increasing neutralization potency against a SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, comprising administering to the subject an effective amount of an anti-SARS-CoV2 multivalent antibody that exhibits increased neutralization potency compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

82. The method of claim 80 or 81, wherein the anti-SARS-CoV2 multivalent antibody exhibits improved prevention of immune escape compared to a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody.

83. The method of any one of claims 80-82, wherein the anti-SARS-CoV2 multivalent antibody exhibits increased neutralization potency compared to a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

84. The method of any one of claims 80-83, wherein the anti-SARS-CoV2 multispecific antibody prevents immune escape of the anti-SARS-CoV2 multivalent antibody for at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 selection rounds as measured by an antibody escape assay.

85. The method of any one of claims 80-84, wherein the anti-SARS-CoV2 multispecific antibody prevents immune escape of the anti-SARS-CoV2 multivalent antibody following at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 exposures to the subject by the SARS-CoV2 virus.

86. The method of any one of claims 80-85, wherein the anti-SARS-CoV2 multispecific antibody is at least 100-fold, at least 500-fold, at least 1,000-fold, or at least 2,000- fold more effective in inhibiting growth of the SARS-CoV2 virus compared to (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 multivalent antibody and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that binds to the same antigens as the anti-SARS-CoV2 multivalent antibody.

87. The method of any one of claims 80-86, wherein the anti-SARS-CoV2 multivalent antibody comprises a first antigen binding site that specifically binds to a SARS-CoV-2 protein and a second antigen binding site that specifically binds to a SARS-CoV-2 protein.

88. The method of claim 87, wherein the first antigen binding site is different than the second antigen binding site.

89. The method of claim 87 or 88, wherein the first antigen binding site comprises a first heavy chain variable domain and a first light chain variable domain, and the second antigen binding site comprises a second heavy chain variable domain and a second light chain variable domain.

90. The method of claim 89, wherein the first and second heavy chain variable regions each comprise CDR1, CDR2 and CDR3 regions, and the first and second light chain variable region each comprise CDR1, CDR2 and CDR3 regions.

91. The method any one of claims 80-90, wherein: the CDR1 of the first heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241,249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; the CDR2 of the first heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242,250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; the CDR3 of the first heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243,251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; the CDR1 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; the CDR2 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence ofLGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS);the CDR3 of the first light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349; the CDR1 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241,249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; the CDR2 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242,250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; the CDR3 of the second heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243,251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; the CDR1 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; the CDR2 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence ofLGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); andthe CDR3 of the second light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349.

92. The method of any one of claims 80-91, wherein: the first heavy chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs: 1, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359; the first light chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346; the second heavy chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359; and the second light chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346.

93. The method of any one of claims 80-92, wherein the anti-SARS-CoV2 multivalent antibody further comprises a third antigen binding domain.

94. The method of claim 93, wherein the third antigen binding site is different than the first antigen binding site, the second antigen binding site, or both the first and second antigen binding sites.

95. The method of claim 93 or 94, wherein the third antigen binding site comprises a third heavy chain variable domain and a third light chain variable domain.

96. The method of any one of claims 80-95, wherein the third heavy chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs: l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359; and the third light chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346.

97. The method of any one of claims 80-96, wherein the third heavy chain variable region comprises CDR1, CDR2 and CDR3 regions.

98. The method of any one of claims 80-97, wherein: the CDR1 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241,249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; the CDR2 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242,250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; the CDR3 of the third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243,251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; the CDR1 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; the CDR2 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23(having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence ofLGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); and the CDR3 of the third light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 154, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349.

99. The method of any one of claims 80-98, wherein the anti-SARS-CoV2 multivalent antibody further comprises a fourth antigen binding domain.

100. The method of claim 99, wherein the fourth antigen binding site is different than one or more of the first, second and third antigen binding sites.

101. The method of claim 99 or 100, wherein the first, second, third and fourth antigen binding sites are different.

102. The method of any one of claims 80-101, wherein the fourth antigen binding site comprises a third heavy chain variable domain and a fourth light chain variable domain.

103. The method of any one of claims 80-102, wherein the fourth heavy chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs: l, 9, 17, 25, 33, 147, 159, 167, 175, 183, 190, 192, 200, 208, 216, 224, 232, 240, 248, 256, 264, 272, 280, 288, 296, 304, 306, 308, 310, 312, 314, 316, 318, 326, 334, 342, 351, 353, 357 and 359; and the fourth light chain variable domain comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to any one of SEQ ID NOs:5, 13, 21, 29, 37, 151, 155, 163, 171, 179, 188, 189, 191, 196, 204, 212, 220, 228, 236, 244, 252, 260, 268, 276, 284, 292, 300, 305, 307, 309, 311, 313, 315, 317, 322, 330, 338 and 346.

104. The method of any one of claims 80-103, wherein the fourth heavy chain variable region comprises CDR1, CDR2 and CDR3 regions.

105. The method of claim 104, wherein: the CDR1 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:2, 10, 18, 26, 34, 148, 160, 168, 176, 184, 193, 201, 209, 217, 225, 233, 241,249, 257, 265, 273, 281, 289, 297, 319, 327, 335 and 343; the CDR2 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:3, 11, 19, 27, 35, 149, 161, 169, 177, 185, 194, 202, 210, 218, 226, 234, 242,250, 258, 266, 274, 282, 290, 298, 320, 328, 336 and 344; the CDR3 of the fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:4, 12, 20, 28, 36, 150, 162, 170, 178, 186, 195, 203, 211, 219, 227, 235, 243,251, 259, 267, 275, 283, 291, 299, 321, 329, 337 and 345; the CDR1 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:6, 14, 22, 30, 38, 152, 156, 164, 172, 180, 197, 205, 213, 221, 229, 237, 245, 253, 261, 269, 277, 285, 293, 301, 323, 331, 339 and 347; the CDR2 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence of GAS), 31 (having the sequence of DAS), and 39 (having the sequence of GAS), 153, 157, 165 (having the sequence of GAS), 173 (having the sequence ofLGS), 181, 198 (having the sequence of DAS), 206 (having the sequence of DVS), 214 (having the sequence of EDS), 222 (having the sequence of KDS), 230 (having the sequence of DAS), 238 (having the sequence of AAS), 246 (having the sequence of GAS), 254 (having the sequence of DDS), 262 (having the sequence of KDS), 270 (having the sequence of SAS), 278 (having the sequence of SAS), 286 (having the sequence of GAS), 294 (having the sequence of GAS), 302 (having the sequence of GAS), 324 (having the sequence of GAS), 332 (having the sequence of DAS), 340 (having the sequence of SAS) and 348 (having the sequence of GAS); andthe CDR3 of the fourth light chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99% or 100% identity to any one of SEQ ID NOs:8, 16, 24, 32, 40, 158, 166, 174, 182, 199, 207, 215, 223, 231, 239, 247, 255, 263, 271, 279, 287, 295, 303, 325, 333, 341 and 349.

106. The method of any one of claims 80-105, wherein the anti-SARS-CoV2 multivalent antibody is the antibody or antigen binding fragment thereof of any one of claims 43- 48.

107. The method of any one of claims 80-106, wherein the antigen is the SARS-CoV-2 protein.

108. The method of any one of claims 80-107, wherein the SARS-CoV2 virus is a SARS-CoV2 variant.

109. The method of claim 108, wherein the SARS-CoV2 variant is Alpha variant(B.1.1.7), Beta variant (B.1.351), Gamma variant (P.1), Delta variant, Epsilon variant (B.1.427), or Omicron variant (B.1.1.529), or a combination thereof.

110. The method of claim 109, wherein the Omicron variant is BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ. l, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ. l, XBB, XBB1.5, BF.7, CH.1.1, or a combination thereof.

111. The method of any one of claims 71-110, further comprising administering to the subject an effective amount of an additional pharmaceutical agent.

112. The method of any one of claims 71-110, further comprising administering to the subject an effective amount of a pharmaceutical composition comprising (i) an additional pharmaceutical agent and (ii) a pharmaceutically acceptable carrier.

113. The method of claim 111 or 112, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, an agent that potentiates vitamin D action, an anti-viral agent, an anti- malarial agent, an antibiotic, or a combination thereof.

114. The method of claim 113, wherein the additional pharmaceutical agent is 25- hydroxyvitamin D.

115. The method of claim 113, wherein the agent that potentiates vitamin D action is a CYP24 inhibitor, 1,25-dihydroxyvitamin D compound, or a combination thereof.

116. The method of claim 113, wherein the anti-viral agent is an anti-retroviral agent, an antibody against SARS-CoV-2 virus, an inhibitor of reverse transcriptase, or a combination thereof.

117. The method of claim 113, wherein the anti-viral agent is maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of aciclovir, ganciclovir, cidofovir, forcamet, ribavirin, interferon alpha, pegylated interferon alpha, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peremivir, valaciclovir, penciclovir, valganciclovir, foscamet, tenofovir, adefovir, entecavir, lamivudine, telbivudine, ribavirin, glecaprevir, grazoprevir, paritaprevir, simeprevir, voxilaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofobuvir, bebtelovimab, or a combination thereof.

118. The method of claim 117, wherein the anti-viral agent is bebtelovimab.

119. The method of claim 113, wherein the anti-viral agent is Retrovir® (3'-azido-3'- deoxypyrimidine, zidovudine), 3 '-azido-3 '-deoxythymidine (AZT), HMD® (2', 3'- dideoxy cytidine, zalcitabine), VidexEC® (2', 3 'dideoxyinosine, didanosine), Epivir® (lamivudine), Zerit® (stavudine), Viread® (tenofovir DF), Ziagen® (abacavir), Emtriva® (emtricitabine, FTC), Rescriptor® (delavirdine), Sustiva® (efavirenz), Viramune® (nevirapine, l l-cyclopropyl-4-methyl-5,l l-dihydro-6H-dipyrido[3,2-b:2',3'-e][l,4]diazepin-6-one), trisodium phosphonoformate, ammonium -21 -tungstenato-9-antimonate, 1 -P-D-ribofuranoxyl- 1 ,2,4- triazole-3 -carboxamide, Aganerase® (amprenavir), Reyataz® (atazanavir), Lexiva® (fosamprenavir), Crixivan® (indinavir), Viracept® (nelfinavir), Norvir® (ritonavir), Fortovase® or Invirase® (saquinavir), lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy-6-phenyl- 2(R)(2,3,4-trimethoxyphenylmethyl)-hexanoyl-(L)-valyl-N-(2-metoxy-ethyl)-amide), adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011 BS (palinavir), polymannoacetate, Fuzeon® (enfuvirtide, T-20), Epzicom® (abacavir and lamivudine), Trizivir® (abacavir, lamivudine and zidovudine), Truvada® (emtricitabine andtenofir DF), Combivir® (lamivudine and zidovudine), Kaletra® (lopinavir and ritonavir), or a combination thereof.

120. The method of any one of claims 111-119, wherein the additional pharmaceutical agent is administered before the antigen binding polypeptide complex, antibody or antigen binding fragment thereof.

121. The method of any one of claims 111-119, wherein the additional pharmaceutical agent is administered after the antigen binding polypeptide complex, antibody or antigen binding fragment thereof.

122. The method of any one of claims 111-119, wherein the additional pharmaceutical agent is administered concurrently with the antigen binding polypeptide complex, antibody or antigen binding fragment thereof.

123. The method of any one of claims 111-119 and 122, wherein the additional pharmaceutical agent and the antigen binding polypeptide complex, antibody or antigen binding fragment thereof are administered in the same pharmaceutical composition.

124. The method of any one of claims 111-123, wherein the additional pharmaceutical agent and the antigen binding polypeptide complex, antibody or antigen binding fragment thereof are administered in different pharmaceutical compositions.

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