Anti-SARS-CoV-2 antigen-binding polypeptide, polypeptide complex, and method of using the same

Abstract

Antigen-binding antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) having certain structural and / or functional features are disclosed. 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

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Application No. 63 / 357,336, filed Jun. 30, 2022; U.S. Provisional Application No. 63 / 357,873, filed Jul. 1, 2022; U.S. Provisional Application No. 63 / 404,473, filed Sep. 7, 2022; U.S. Provisional Application No. 63 / 381,850, filed Nov. 1, 2022; and U.S. Provisional Application No. 63 / 433,719, filed Dec. 9, 2022, all of which are hereby incorporated by reference in their entirety.

[0002] Reference to Electronically Submitted Sequence Listing The content of the electronically submitted sequence listing (Name: 4850_0100003_SEQLISTING_ST26.xml; Size: 486,871 bytes; Creation Date: Jun. 28, 2023) is hereby incorporated by reference in its entirety.

[0003] Field 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 characteristics. 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.

[0004] Description of Federally Sponsored Research or Development This invention was made in the performance of a joint research and development contract with the National Institutes of Health, an agency of the Department of Health and Human Services. The government has certain rights in this invention.

Background Art

[0005] Background The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused more than 450 million infections and over 6 million deaths worldwide. SARS-CoV-2 is a strain of coronavirus that causes COVID-19 (Coronavirus Disease 2019). Sequencing and publication of the original Wuhan Hu-1 (WA-1) genome enabled the generation of spike proteins for rapid vaccine design and therapeutic antibody development. However, the persistent circulation of the virus during the human pandemic has led to genetic variations that are resistant to containment and eradication. Cellular and humoral immune responses are required for optimal protection against viral infection, while neutralizing antibodies play a major role in the prevention and eradication of pathogens.

[0006] SARS-CoV-2 spike protein variants and SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Epsilon variant (B.1.427), and Omicron (B.1.1.529) have emerged to be resistant to current therapies, have increased pathogenicity, and contain mutations that evade current vaccines. This has led to their classification as Variants of Concern (VOCs).

[0007] Therapeutic antibodies have emerged as an important class of drugs for treating human diseases and disorders. Therapeutic antibodies are engineered to have specificity for two or more different antigens or epitopes (i.e., “multispecific” antibodies that are, for example, bispecific, trispecific, or tetravalent). Multispecific antibodies are used to form multi-targeted strategies for treating human diseases and disorders and are an important technological platform for developing neutralizing antibody-based therapeutics for the prevention and treatment of SARS-CoV-2 infection and COVID-19.

[0008] There is a need for improved therapies for preventing and treating SARS-CoV-2 infection and COVID-19. There is a need for therapeutic antibodies having 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 obtain an effective immune response via vaccination.

Summary of the Invention

[0009] Brief Summary Disclosed 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; the second polypeptide has a structure represented by VH1-L2-CH1; the third polypeptide has a structure represented by VH2-L3-VH3-L4-CH1; the fourth polypeptide has a structure represented by VL3-L5-VL2-L6-CL; 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; CH1 is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-6 are amino acid linkers. An antigen-binding polypeptide complex is provided.

[0010] Also, in the present specification, there is provided an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; the first polypeptide has a structure represented by VL1-L1-CL; the second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; the third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; the fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL; 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 containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is immunoglobulin light chain constant region; and L1 to 8 are amino acid linkers.

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

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

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

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

[0015] In some embodiments, VH1, VH2, and VH3 each contain different heavy chain variable regions, and VL1, VL2, and VL3 each contain different light chain variable regions.

[0016] In some embodiments, VH1, VH2, and VH3 each independently comprise a CDR1 having an amino acid sequence with 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 having an amino acid sequence with 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 having an amino acid sequence with 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; VL1, VL2, and VL3 each independently comprise a CDR1 having an amino acid sequence with 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;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 NO: 7 (having the sequence of SAS), 15 (having the sequence of GTN), 23 (having the sequence 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 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 NO: 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 embodiments, 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 embodiments, 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; 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 with SEQ ID NO: 32.;

[0019] In some embodiments, 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 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; 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 with SEQ ID NO: 32.;

[0020] In some embodiments, 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; 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 with SEQ ID NO: 32.;

[0021] In some embodiments, 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 15 (having the sequence of GTN);and comprising 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 with 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 with 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 with 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 with SEQ ID NO: 24; 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 with 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 with 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 with SEQ ID NO: 32.;

[0022] In some embodiments, 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 comprises 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 with 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 with 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 with 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 with SEQ ID NO: 32; 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 with 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 with 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 with SEQ ID NO: 24.;

[0023] In some embodiments, 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 comprises 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 with 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 with 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 with 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 with SEQ ID NO: 16; 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 with 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 with 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 with SEQ ID NO: 24.;

[0024] In some embodiments, 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 31 (having the sequence of DAS);and comprises 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 with 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 with 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 with 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 with SEQ ID NO: 24; 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 with 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 with 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 with SEQ ID NO: 16.;

[0025] In some embodiments, 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 with 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. In some embodiments, the sequence has, for example, at SEQ ID NO: 175, a mutation at N62, for example, N62Q or N62Q.

[0026] In some embodiments, 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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 embodiments, the immunoglobulin hinge comprises an upper hinge region, a central hinge region, a lower hinge region, or a combination thereof.

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

[0037] In some embodiments, 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 (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, SEQ ID NO: 50 has the sequence of ASG).

[0038] In some embodiments, one or more of linkers L1-8 are non-immunogenic.

[0039] In some embodiments, one or more of linkers L1-8 do not contain a consensus T cell epitope.

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

[0041] In some embodiments, the antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the knob-into-hole modification comprises, based on the EU numbering scheme, (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) combinations thereof. In some embodiments, the hole substitutions are M428L and N434S based on the EU numbering scheme. In some embodiments, the hole substitution is N434A based on the EU numbering scheme.

[0042] In some embodiments, the antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the Fc effector function knockout mutation is L234A, L235A, P239A, or combinations thereof based on the EU numbering scheme.

[0043] In some embodiments, the antigen-binding polypeptide complex comprises a detectable label. In some embodiments, the detectable label is a radioactive label, chemiluminescent label, fluorescent label, enzyme, peptide tag, or combinations thereof. In some embodiments, the peptide tag is a polyhistidine tag consisting of about 4 to about 10 histidine residues. In some embodiments, the polyhistidine tag consists of about 8 histidine residues.

[0044] In some embodiments, the antigen-binding polypeptide complex specifically binds to a SARS-CoV-2 protein having an equilibrium dissociation constant (K fD ) of about 10 μM to about 1 pM.

[0045] In some embodiments, the variable region of the antibody may require site-specific deglycosylation. In some embodiments, for the E8 VH mAb, an N62 mutation is made to remove high mannose glycosylate residues or sites. Preferred mutations include, but are not limited to, N62Q or N62S.

[0046]

[0045] In some embodiments, the SARS-CoV-2 virus is the original Wuhan strain (WA1), the D614G spike protein variant (D614G), the alpha variant (B.1.1.7), the beta variant (B.1.351), the gamma variant (P.1), the kappa variant (B.1.617.1), the delta variant (B.1.617.2 or AY.1), the epsilon variant (B.1.427), the iota variant (B.1.526), the lambda variant (C.37), the mu variant (B.1.621), the C.1.2 variant, the omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

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

[0048] Also, provided herein are antibodies or antigen-binding fragments thereof that include the antigen-binding polypeptide complexes provided herein. In some embodiments, the antibody is IgG, IgM, IgE, IgA, or IgD. In some embodiments, IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the antigen-binding fragment is Fab, scFab, Fab’, F(ab’)2, Fv, or scFv. In some embodiments, the antibody is human or humanized. In some embodiments, the antibody is a monoclonal antibody, an engrafted antibody, or a chimeric antibody.

[0049] Also, provided herein is a multivalent anti-SARS-CoV2 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 multivalent anti-SARS-CoV2 antibody, and / or (ii) a combination of monovalent anti-SARS-CoV2 antibodies that bind to the same antigen as the multivalent anti-SARS-CoV2 antibody.

[0050] Also provided herein are pharmaceutical compositions comprising the antigen-binding polypeptides, antigen-binding polypeptide complexes, antibodies or antigen-binding fragments thereof provided herein. In some embodiments, 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 embodiments, the pharmaceutical composition comprises (1) one or more polynucleotides encoding an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) provided herein, and (2) a carrier selected from the group consisting of a lipid or lipid nanoparticle. In some embodiments, the one or more polynucleotides encoding an antigen-binding polypeptide or antigen-binding polypeptide complex are stabilized polynucleotides that are resistant to degradation or breakdown in vivo. In some embodiments, the stabilized polynucleotide is capped at one end (5' cap) and has a long polyadenylation (polyA) tail at the other end to form a stabilized mRNA with 5' and 3' UTRs. In some embodiments, the polyA tail is about 50 bp, about 100 bp, about 120 bp, or about 150 bp. In some embodiments, modified nucleosides can be incorporated into the mRNA to increase translation and / or reduce potential immunogenicity.

[0051] Also provided herein are pharmaceutical compositions comprising the antigen-binding polypeptide complexes, antibodies or antigen-binding fragments thereof provided herein, and an additional pharmaceutical agent.

[0052] Also provided herein are kits comprising the antigen-binding polypeptide complexes, antibodies or antigen-binding fragments thereof provided herein, or a pharmaceutical composition.

[0053] Also provided herein is a method of preventing or treating 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 a therapeutic antigen-binding polypeptide or antigen-binding polypeptide complex can be by direct administration of the therapeutic agent or by an indirect method that includes administering to a patient in need thereof a modified mRNA composition encoding a therapeutic antigen-binding polypeptide or antigen-binding polypeptide complex from which the therapeutic antigen-binding polypeptide or antigen-binding polypeptide complex is translated.

[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 for diagnosing a subject as being infected with or suspected of being infected with the 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 containing the polypeptide complex, antibody or fragment and the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as being infected with or suspected of being infected with the SARS-CoV-2 virus if the presence of the virus complex is detected.

[0056] Also provided herein is a method for diagnosing a subject as not being infected with or not suspected of being infected with the 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 containing the polypeptide complex, antibody or fragment and the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as not being infected with or not suspected of being infected with the SARS-CoV-2 virus if the presence of the virus complex is not detected.

[0057] Also provided herein is a method for diagnosing a subject as having COVID-19 or as 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 polypeptide complex, antibody or fragment and a virus complex containing the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as having COVID-19 or as suspected of having COVID-19 if the presence of the virus complex is detected.

[0058] Also provided herein is a method for diagnosing a subject as not having COVID-19 or as 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 polypeptide complex, antibody or fragment and a virus complex containing the SARS-CoV-2 virus, its virion or fragment; and (iii) diagnosing the subject as not having COVID-19 or as not suspected of having COVID-19 if the presence of the virus complex is not detected.

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

[0060] In some embodiments, 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 embodiments, the SARS-CoV-2 virus is the original Wuhan strain (WA1), the D614G spike protein variant (D614G), the alpha variant (B.1.1.7), the beta variant (B.1.351), the gamma variant (P.1), the kappa variant (B.1.617.1), the delta variant (B.1.617.2 or AY.1), the epsilon variant (B.1.427), the iota variant (B.1.526), the lambda variant (C.37), the mu variant (B.1.621), the C.1.2 variant, the omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

[0062] In some embodiments, the SARS-CoV-2 virus is the original Wuhan strain (WA1), the D614G spike protein variant (D614G), the alpha variant (B.1.1.7), the beta variant (B.1.351), the gamma variant (P.1), the kappa variant (B.1.617.1), the delta variant (B.1.617.2 or AY.1), the epsilon variant (B.1.427), the iota variant (B.1.526), the lambda variant (C.37), the mu variant (B.1.621), the C.1.2 variant, the omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

[0063] Also provided herein is a method for preventing immune evasion of the SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, the method 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 for preventing immune evasion of the SARS-CoV2 virus in a subject infected with the SARS-CoV2 virus, the method comprising administering to the subject an effective amount of a polyclonal anti-SARS-CoV2 antibody that exhibits improved prevention of immune evasion as compared to (i) a monoclonal anti-SARS-CoV2 antibody that binds to one of the same antigens as the polyclonal anti-SARS-CoV2 antibody, and / or (ii) a combination of monoclonal anti-SARS-CoV2 antibodies that bind to the same antigen as the polyclonal anti-SARS-CoV2 antibody.

[0065] Also provided herein is a method for neutralizing the SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, the method 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 for increasing the neutralizing potency against the SARS-CoV-2 virus in a subject infected with the SARS-CoV2 virus, the method 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 for increasing the neutralizing potency against SARS-CoV-2 virus in a subject infected with SARS-CoV-2 virus, comprising administering to the subject an effective amount of an anti-SARS-CoV-2 multivalent antibody that exhibits increased neutralizing potency as compared to (i) a monovalent anti-SARS-CoV-2 antibody that binds to one of the same antigens as the anti-SARS-CoV-2 multivalent antibody and / or (ii) a combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as the anti-SARS-CoV-2 multivalent antibody.

Brief Description of the Drawings

[0068] Some embodiments of the present invention are described herein by way of example only with reference to the accompanying drawings. It is emphasized that the details shown are illustrative and for the purpose of a case-by-case discussion of embodiments of the present invention.

[0069]

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[0070] **Detailed Description of the Invention** Provided herein are antigen-binding polypeptides and polypeptide complexes having improved characteristics. In some embodiments, the antigen-binding polypeptides and polypeptide complexes have broad reactivity against SARS-CoV-2 variants of concern (VOCs), high neutralizing potency, and / or resistance to SARS-CoV-2 evasion. In some embodiments, the antigen-binding polypeptides and polypeptide complexes provided herein are easier to manufacture and administer than current therapeutic antibody cocktails. In some embodiments, the antigen-binding polypeptides and polypeptide complexes treat and / or prevent SARS-CoV-2 infection and / or COVID-19 in immunocompromised individuals who cannot obtain an effective immune response through vaccination.

[0071] Various terms related to the embodiments of the present disclosure are used throughout this specification and the claims. Such terms should be given their ordinary meaning in the art, unless otherwise indicated. Other specially defined terms should be interpreted in accordance with the definitions provided herein.

[0072] Definition As used herein, the term "SARS-CoV-2" refers to "severe acute respiratory syndrome coronavirus 2". SARS-CoV-2 is a strain of coronavirus that causes coronavirus disease 2019 (COVID-19).

[0073] As used herein, the term "SARS-CoV-2 virus" includes the SARS-CoV-2 virus, its virions or fragments.

[0074] As used herein, the term "COVID-19" refers to "coronavirus disease 2019". COVID-19 is caused by the SARS-CoV-2 virus. The symptoms of COVID-19 are varied but often include fever, cough, headache, fatigue, difficulty breathing, loss of smell, and loss of taste. Symptoms can start 1 to 14 days after exposure to the virus; however, at least one-third of infected people do not develop noticeable symptoms. Of those who develop symptoms noticeable enough to be classified as patients, most develop mild to moderate symptoms (up to mild pneumonia), approximately 15% develop severe symptoms (difficulty breathing, hypoxemia, or more than 50% lung lesions on imaging), and approximately 5% develop critical symptoms (respiratory failure, shock, or multi-organ dysfunction). Some people continue to experience various effects for months after recovery ("long COVID").

[0075] As used herein, the term "SARS-CoV-2 protein" refers to any protein associated with the SARS-CoV-2 virus. The SARS-CoV-2 virus is composed of 16 non-structural proteins and 4 structural proteins. The non-structural proteins are mainly involved in viral replication. The structural proteins include the membrane protein, nucleocapsid protein, envelope protein, and spike protein, which are involved in viral assembly and infection. The spike protein has two subunits S1 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. While S1 specifically binds hACE2 via its receptor-binding domain (RBD), S2 facilitates the fusion of the virus to the cell membrane. Thus, as used herein, SARS-CoV-2 proteins include, but are not limited to, the membrane protein, nucleocapsid protein, envelope protein, or spike protein, or combinations thereof. In some embodiments, the SARS-CoV-2 protein is the spike protein.

[0076] In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) provided herein is a class I antibody, class II antibody, or class III antibody, or a portion thereof.

[0077] As used herein, "Class I" typically refers to an antibody that contains a short heavy chain CDR3 region, competes with angiotensin-converting enzyme 2 (ACE2) for binding to the receptor-binding domain (RBD) of the spike protein, and recognizes only the "upward" conformation of the RBD. See, e.g., Shrestha et al., Front. Immunol. 12:7520003, 2021. As used herein, "Class II" typically refers to an antibody that has a long heavy chain CDR3 loop, competes with ACE2 for binding to the RBD, and is capable of binding to the RBD in both "upward" and "downward" conformations. As used herein, "Class III" refers to an antibody that is capable of binding to the RBD in both "upward" and "downward" conformations and typically binds outside the ACE2-binding region. As used herein, "Class IV" refers to an antibody that binds to a highly conserved potential epitope on the RBD outside the receptor-binding motif (RBM) of the spike protein.

[0078] In some embodiments, the antigen-binding polypeptides or antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) provided herein belong to two, three, or four classes. Thus, in some embodiments, the antigen-binding polypeptides or antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) provided herein are Class I and II antibodies, Class I and III antibodies, Class I and IV antibodies, Class II and III antibodies, Class II and IV antibodies, Class III and IV antibodies, Class I, II, and III antibodies, Class I, II, and IV antibodies, Class I, III, and IV antibodies, Class II, III, and IV antibodies, or Class I, II, III, and IV antibodies.

[0079] In some embodiments, the 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 embodiments, VH1 and VL1 and / or VH3 and VL3 are class III antigen-binding sites. In some embodiments, VH2 and VL2 and / or VH4 and VL4 are class I antigen-binding sites. In some embodiments, 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 embodiments, VH1 and VL1 are class II antigen-binding sites. In some embodiments, VH2 and VL2 are class I antigen-binding sites. In some embodiments, VH3 and VL3 are class I antigen-binding sites. In some embodiments, VH4 and VL4 are class III antigen-binding sites. In some embodiments, 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.

[0080] 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 protrude from the surface of the SARS-CoV-2 virion and mediate the entry of the virion into host cells. The SARS-CoV-2 spike protein is also referred to as the "spike (S) glycoprotein" and "E2". The structural and functional properties of this protein have been characterized. See, for example, Huang et al., Acta Pharmacol. Sin. 41:1141-1149, 2020; Wu et al., Nature 579(7798):265-269, 2020; and Gene ID:43740568.

[0081] Antigen-binding sequences for anti-SARS-CoV-2 proteins (e.g., CDRs, VH, VL, heavy and light chain sequences from antibodies) are known and are described, for example, in U.S. Application No. 63 / 147,419. Such sequences include, but are not limited to, SEQ ID NOs: 1-40, 81-186, and 188-360.

[0082] 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).

[0083] 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). Antigen-binding polypeptide complexes include, but are not limited to, antibodies or antigen-binding fragments thereof.

[0084] The term "antibody" includes, but is not limited to, glycoprotein immunoglobulins that specifically bind to an antigen and contain at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each H chain includes a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region includes three constant domains, CH1, CH2, and CH3. Each light chain includes a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region includes one constant domain, CL. The VH and VL regions can be further subdivided into hypervariable regions called complementarity determining regions (CDRs) incorporated into more conserved regions called framework regions (FRs). Each VH and VL contains three CDRs and four FRs arranged in the following order from amino terminus to carboxy - terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain the binding domains that interact with the antigen. The constant region of the antibody can 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 of the classical complement system (C1q). The heavy chain may or may not have a C - terminal lysine. Unless otherwise specified herein, 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.

[0085] The term "monoclonal antibody" as used herein refers to an antibody produced by a single clone of B cells and that binds to the same epitope. In contrast, the term "polyclonal antibody" refers to a population of antibodies produced by different B cells and that 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; fully synthetic antibodies; and single - chain antibodies. Non - human antibodies can be humanized by recombinant methods to reduce their immunogenicity in humans.

[0086] The antibody can be an antibody that has been modified (e.g., by mutation, deletion, substitution, conjugation to a non-antibody moiety). For example, the antibody can contain one or more variant amino acids that change the properties of the antibody (e.g., functional properties) as compared to a naturally occurring antibody. For example, several such modifications that affect half-life, effector function, and / or the immune response to the antibody in a patient are known in the art. The term antibody also includes artificial polypeptide constructs that contain at least one antibody-derived antigen-binding site.

[0087] An "antigen-binding fragment" of an antibody refers to one or more fragments or portions of an antibody that retain the ability to specifically bind to an antigen bound by the intact antibody. It has been shown that the antigen-binding function of an antibody can be exerted by fragments or portions of the full-length antibody. The antigen-binding fragment can contain the antigen-determining regions of the intact antibody (e.g., complementarity-determining regions (CDRs)). Examples of antigen-binding fragments of an antibody include, but are not limited to, Fab, Fab’, F(ab’)2, and Fv fragments, linear antibodies, and single-chain antibodies. The antigen-binding fragment of an antibody can be derived from any animal species, e.g., rodents (e.g., mouse, rat, or hamster) and humans, or can be artificially produced.

[0088] Furthermore, the two domains of the Fv fragment, namely, VL and VH, are encoded by separate genes, but they can be connected using recombinant methods by a synthetic linker that enables the VL and VH regions to pair to form a single protein chain that forms a monovalent molecule (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 by the term "antigen-binding fragment" of an antibody.

[0089] Antigen-binding fragments are obtained using conventional techniques known to those skilled in the art and the fragments are screened for utility in the same manner as intact antibodies. Antigen-binding fragments can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact immunoglobulins.

[0090] As used herein, the term "variable region" typically refers to a portion of an antibody, usually a portion of a light or heavy chain, typically approximately the amino-terminal 110-120 amino acids, or 110-125 amino acids in a mature heavy chain and approximately 90-115 amino acids in a mature light chain, which varies extensively in sequence between antibodies and is 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), whereas the more highly conserved regions in the variable domains are called framework regions (FRs). Without wishing to be bound by any particular mechanism or theory, the CDRs of the light and heavy chains are thought to be primarily responsible for the antibody's interaction and specificity with the antigen. In some embodiments, the variable region is a mammalian variable region, such as a human, mouse or rabbit variable region. In some embodiments, the variable region comprises rodent or murine CDRs and human framework regions (FRs). In some embodiments, the variable region is a primate (e.g., non-human primate) variable region. In some embodiments, the variable region comprises rodent or murine CDRs and primate (e.g., non-human primate) framework regions (FRs).

[0091] The term "complementarity-determining region" or "CDR" as used herein refers to each of the regions of an antibody variable domain that have sequences that are hypervariable and / or form structurally defined loops (hypervariable loops) and / or contain antigen contact residues. An antibody can contain six CDRs, for example, three in VH and three in VL.

[0092] The terms "VL", "VL region", and "VL domain" are used interchangeably herein to refer to the variable light chain region of an antigen-binding polypeptide, an antigen-binding polypeptide complex, an antibody, or an antigen-binding fragment thereof. In some embodiments, the VL region is referred to herein as VL1 to denote the first variable light chain region, VL2 to denote the second variable light chain region, VL3 to denote the third variable light chain region, and VL4 to denote the fourth variable light chain region. The recited VL regions (e.g., VL1) may have the same or different antigen-binding properties and / or the same or different sequences as another recited VL region (e.g., VL2).

[0093] The terms "VH", "VH region", and "VH domain" are used interchangeably herein to refer to the variable heavy chain region of an antigen-binding polypeptide, an antigen-binding polypeptide complex, an antibody, or an antigen-binding fragment thereof. In some embodiments, the VH region is referred to herein as VH1 to denote the first variable heavy chain region, VH2 to denote the second variable heavy chain region, and VH3 to denote the third variable heavy chain region. The recited VH regions (e.g., VH1) may have the same or different antigen-binding properties and / or the same or different sequences as another recited VH region (e.g., VH2).

[0094] As used herein, the term "Kabat numbering" and similar terms are recognized in the art and refer to a system for numbering amino acid residues in the heavy and light chain variable regions of an antibody or antigen-binding fragment thereof. In some embodiments, the 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, the CDRs within an antibody heavy chain molecule are typically present at amino acid positions 31-35 (CDR1), amino acid positions 50-65 (CDR2), and amino acid positions 95-102 (CDR3), which may optionally include one or two additional amino acids (referred to as 35A and 35B in the Kabat numbering scheme) after position 35. Using the Kabat numbering system, the CDRs within an antibody light chain molecule are typically present at amino acid positions 24-34 (CDR1), amino acid positions 50-56 (CDR2), and amino acid positions 89-97 (CDR3).

[0095] As used herein, the terms "constant region" or "constant domain" are used interchangeably to refer to the carboxyl-terminal portion of a light chain and / or heavy chain that is not directly involved in the binding of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, e.g., to an antigen, but that may exhibit various effector functions such as interaction with the Fc region. The constant region typically has a more conserved amino acid sequence compared to the variable region. In some embodiments, the antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof comprises a constant region or a portion thereof sufficient for antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). The constant region includes, but is not limited to, the light chain constant region (CL) or the heavy chain constant regions (CH1, CH2, CH3).

[0096] 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 several proteins of the complement system. The Fc region typically includes the CH2 and CH3 regions, and optionally, the immunoglobulin hinge.

[0097] As used herein, the terms "immunoglobulin hinge", "hinge", "hinge domain" or "hinge region" are used interchangeably to refer to the extension of the heavy chain between the Fab and Fc portions of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof. The hinge provides structure, location and flexibility that assist in the normal functionality of the antibody (e.g., for cross-linking two antigens or binding two antigenic determinants on the same antigen molecule). The immunoglobulin hinge can be divided into upper, central and lower hinge regions that can be separated based on structural and / or genetic components. The immunoglobulin hinges of the present invention can contain one, two, or all three of these regions. Structurally, the upper hinge region extends from the C-terminus of CH1 to the first hinge disulfide bond. The central hinge region extends 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.

[0098] As used herein, the term "Fab" refers to the region of an antibody that binds to an antigen. It typically consists of one constant and one variable domain of each of the heavy and light chains.

[0099] As used herein, the term "heavy chain" typically refers to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof that consists of a heavy chain variable region (VH), a heavy chain constant region 1 (CH1), a heavy chain constant region 2 (CH2), and a heavy chain constant region 3 (CH3). A typical antibody consists of two heavy chains and two light chains. When used in reference to an antibody, the heavy chain may refer to any distinguishable type, e.g., alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the constant region, which gives rise to the IgA, IgD, IgE, IgG, and IgM classes of antibodies (including subclasses of IgG, e.g., IgG1, IgG2, IgG3, and IgG4), respectively. Heavy chain amino acid sequences are known in the art. In some embodiments, the heavy chain is a human heavy chain.

[0100] As used herein, the term "light chain" typically refers to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof that consists of a light chain variable region (VL) and a light chain constant region (CL). A typical antibody consists of two light chains and two heavy chains. When used in reference to an antibody, the light chain may refer to any distinguishable type, e.g., kappa (κ) or lambda (λ), based on the amino acid sequence of the constant region. Light chain amino acid sequences are known in the art. In some embodiments, the light chain is a human light chain.

[0101] The term "chimeric" antibody or antigen-binding fragment thereof refers to an antibody or antigen-binding fragment thereof whose amino acid sequence is derived from two or more species. Typically, the variable regions of both the light and heavy chains correspond to those of an antibody or antigen-binding fragment thereof from a particular mammalian species (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and potency, while the constant regions are homologous to the sequences in an antibody or antigen-binding fragment thereof from another species (usually human) to avoid inducing an immune response in that species.

[0102] The term "humanized" antibody or antigen-binding fragment thereof refers to a non-human (e.g., murine) antibody or antigen-binding fragment in the form of a specific immunoglobulin chain, chimeric immunoglobulin, or fragment thereof that contains minimal non-human (e.g., murine) sequences. Typically, a humanized antibody or antigen-binding fragment thereof is a human immunoglobulin in which residues from the complementarity-determining regions (CDRs) are replaced by residues from the CDRs of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and capacity (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 embodiments, residues in the framework regions (FRs) of the human immunoglobulin are replaced by the corresponding residues in an antibody or fragment from a non-human species having the desired specificity, affinity, and capacity. A humanized antibody or antigen-binding fragment thereof can be further modified by substitution of additional residues in either the Fv framework region and / or the replaced non-human residues to improve and optimize the specificity, affinity, and / or capacity of the antibody or antigen-binding fragment. Usually, a humanized antibody or antigen-binding fragment thereof contains substantially all of at least one, typically two or three, variable domains that contain all or substantially all of the CDR regions corresponding to the non-human immunoglobulin, while all or substantially all of the FR regions are those of the human immunoglobulin consensus sequence. A humanized antibody or antigen-binding fragment thereof can also include at least a portion of the constant region, typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are known and are described, for example, in U.S. Patent 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).

[0103] As used herein, the term "human" antibody or antigen-binding fragment thereof means an antibody or antigen-binding fragment thereof having an amino acid sequence derived from the human immunoglobulin locus, and such antibody or antigen-binding fragment is made using recombinant techniques known in the art. This definition of human antibody or antigen-binding fragment thereof includes intact or full-length antibodies and fragments thereof.

[0104] An "isolated" polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector or host cell is a polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector or host cell that is not in its natural form. Isolated polypeptides, polypeptide complexes, antibodies, antigen-binding fragments thereof, polynucleotides, vectors or host cells include those that have been purified to the extent that they are no longer in their natural form. In some embodiments, an isolated polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector or host cell is substantially pure. As used herein, "substantially pure" refers to a substance that is at least 50% pure (i.e., free of contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[0105] The terms "polypeptide", "peptide", and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers can be linear or branched, can include modified amino acids, and can be interrupted by non-amino acids. The term also includes amino acid polymers that are naturally or artificially modified; for example, polymers of amino acids modified by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included in the definition are polypeptides containing, for example, one or more analogs of amino acids (including, for example, non-natural amino acids, etc.), as well as other modifications known in the art. Since the polypeptides of the present invention are antibody-based, in some embodiments, it is understood that the polypeptides can occur as single chains or related chains.

[0106] As used herein, "isoelectric point" or "pI" refers 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.

[0107] As used herein, "pH" refers to a quantitative measure of acidity or basicity. This term typically converts the value of the concentration of hydrogen ions in the range of about 1 to 10 -14 gram equivalents per liter to a number from 0 to 14.

[0108] As used herein, "SARS-CoV-2 escape" refers to the process by which the SARS-CoV-2 virus acquires one or more mutations that allow the virus to evade antibodies produced by a particular vaccine.

[0109] As used herein, "SARS-CoV-2 evolution" refers to the genetic changes that the SARS-CoV-2 virus accumulates during its lifespan, which can result from adaptations in response to environmental changes or immune responses in the host.

[0110] The use of alternative means (e.g., "or") is to be understood to mean any one, both, or a combination of them. As used herein, the indefinite articles "a" or "an" are to be understood to refer to "one or more" of any description or recited component.

[0111] As used herein, the term "and / or" is to be construed as a particular disclosure with or without the other of two specified features or components. Thus, the term "and / or", when 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). Similarly, the term "and / or", when used in a phrase such as "A, B, and / or C" herein, is intended to include 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).

[0112] Whenever an aspect is described herein using words such as "comprising", "having", etc., it is understood that other similar aspects described from the perspective of "consisting of" and / or "consisting essentially of" are also provided.

[0113] As used herein, the term "about" refers to a value or composition that is within an acceptable error range for a 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 one or more standard deviations of the mean in accordance with practices in the relevant art. Alternatively, "about" can mean a range of up to 10% or 20% (i.e., ±10% or ±20%). For example, about 3 mg can include any numerical value from 2.7 mg to 3.3 mg (for 10%) or from 2.4 mg to 3.6 mg (for 20%). Further, particularly with respect to biological systems or processes, the term can mean up to one order of magnitude or up to five times the value. Where a particular value or composition is provided in the present application and claims, unless otherwise stated, the meaning of "about" should be assumed to be within the acceptable error range for that particular value or composition.

[0114] As described herein, any numerical range, concentration range, percentage range, ratio range, or integer range is to be understood to include any integer value within the recited range and, where appropriate, fractions thereof (e.g., one-tenth and one-hundredth of an integer), unless otherwise indicated.

[0115] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. For example, 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 Oxford Dictionary Of Biochemistry And Molecular Biology, 2006, Oxford University Press provide many common dictionaries of terms used in this disclosure to those of ordinary skill in the art.

[0116] Units, prefixes, and symbols are shown in their accepted forms of the International System of Units (SI). Numerical ranges include the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure that may be provided by reference to the specification as a whole. Accordingly, the terms defined herein are more fully defined by reference to the entire specification.

[0117] Various aspects are described in more detail in the following sections.

[0118] Antigen-binding polypeptides and polypeptide complexes Provided herein are antigen-binding polypeptides and polypeptide complexes having certain structural features. These features include the cross-over double variable (CODV) structure described in International Publication No. WO2017180913A2.

[0119] In some embodiments, the antigen-binding polypeptide complex provided herein comprises a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; the first polypeptide has a structure represented by VL1-L1-CL; the second polypeptide has a structure represented by VH1-L2-CH1; the third polypeptide has a structure represented by VH2-L3-VH3-L4-CH1; the fourth polypeptide has a structure represented by VL3-L5-VL2-L6-CL; 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; CH1 is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1-6 are amino acid linkers.

[0120] In some embodiments, the antigen-binding polypeptide complex provided herein comprises a first polypeptide, a second polypeptide, a third polypeptide, and a fourth polypeptide; the first polypeptide has a structure represented by VL1-L1-CL; the second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; the third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; the fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL; 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 immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally, an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is immunoglobulin light chain constant region; and L1-8 are amino acid linkers.

[0121] In some embodiments, VH1 and VH3 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some embodiments, VL1 and VL3 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH1 and VH3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and VL1 and VL3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH2 comprises CDR1, CDR2, and / or CDR3 sequences that are different from VH1 and VH3 (e.g., 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 having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and / or VL2 comprises CDR1, CDR2, and / or CDR3 sequences that are different from VL1 and VL3 (e.g., 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 having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some preferred embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 respectively comprises or consists of the corresponding amino acid sequence specified above.

[0122] In some embodiments, VH1 and VH2 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some embodiments, VL1 and VL2 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH1 and VH2 each contain the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and VL1 and VL2 each contain the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH3 comprises CDR1, CDR2, and / or CDR3 sequences that are different from 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 CDR1, CDR2, and / or CDR3 sequences that are different from 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 embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0123] In some embodiments, VH2 and VH3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some embodiments, VL2 and VL3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH2 and VH3 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and VL2 and VL3 each comprise the same CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH1 comprises CDR1, CDR2, and / or CDR3 sequences that are different from VH2 and VH3 (e.g., 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 having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and / or VL1 comprises CDR1, CDR2, and / or CDR3 sequences that are different from VL2 and VL3 (e.g., 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 having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some preferred embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0124] In some embodiments, VH1, VH2, and VH3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some embodiments, VL1, VL2, and VL3 each comprise the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH1, VH2, and VH3 each contain the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and VL1, VL2, and VL3 each contain the same CDR1, CDR2, and / or CDR3 sequence (e.g., 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 with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some preferred embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0125] In some embodiments, VH1, VH2, and VH3 each comprise different CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some embodiments, VL1, VL2, and VL3 each comprise different CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity).In some embodiments, VH1, VH2, and VH3 each contain different CDR1, CDR2, and / or CDR3 sequences (e.g., 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 an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity), and VL1, VL2, and VL3 each contain different CDR1, CDR2, and / or CDR3 sequences (e.g., 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 and an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity). In some preferred embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0126] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) each independently comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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 embodiments, each of the CDR1, CDR2, and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0127] In some embodiments, VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) each independently comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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; SEQ ID NO: 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 a CDR2 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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 the foregoing;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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0128] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) each independently comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3;VL1, VL2, and VL3) each independently contain a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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; SEQ ID NO: 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 a CDR2 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at 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 these;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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0129] In some embodiments, 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 embodiments, 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 embodiments, 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.

[0130] In some embodiments, 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 embodiments, 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 embodiments, 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.

[0131] In some embodiments, 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; 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 embodiments, VH1, VH2, and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VL1, VL2, and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.

[0132] In some embodiments, 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 least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, VH1 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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.

[0133] In some embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; 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.

[0134] In some embodiments, 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 least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 contain a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL2 contains a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, VH1 and VH3 each contain a CDR1 having an amino acid sequence with at least 90% identity to SEQ ID NO: 18;A CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VL1 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.;

[0135] In some embodiments, 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%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 28.In some preferred embodiments, VH1 and VH2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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.

[0136] In some embodiments, 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; 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 embodiments, VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.

[0137] In some embodiments, 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 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 and VL2 each include a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL3 includes a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, VH1 and VH2 each include a CDR1 having an amino acid sequence with at least 90% identity to SEQ ID NO: 18;A CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VL1 and VL2 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.;

[0138] In some embodiments, 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% 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 embodiments, VH2 and VH3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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.

[0139] In some embodiments, 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; 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.In some preferred embodiments, 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; 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 embodiments, 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; 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.

[0140] In some embodiments, 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% 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;VL2 and VL3 each include 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 with 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 with 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 with SEQ ID NO: 24; VL1 includes 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 with 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 with 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 with SEQ ID NO: 32. In some preferred embodiments, VH2 and VH3 each include a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19;and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VL2 and VL3 each comprise a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.;

[0141] In some embodiments, 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 least 90%, at least 91%, at least 92%, at least 93%, at 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 with 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 with 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 with SEQ ID NO: 28. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 containing the amino acid sequence of SEQ ID NO: 18; a CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a CDR3 containing the amino acid sequence of SEQ ID NO: 20; VH3 comprises a CDR1 containing the amino acid sequence of SEQ ID NO: 26; a CDR2 containing the amino acid sequence of SEQ ID NO: 27; and a CDR3 containing the amino acid sequence of SEQ ID NO: 28.;

[0142] In some embodiments, 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;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 embodiments, 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; 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 comprises a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 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 GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 24; 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 DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 32.;

[0143] In some embodiments, 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 least 90%, at least 91%, at least 92%, at least 93%, at 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 24; 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 with 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 with 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 with SEQ ID NO: 32. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11;and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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 comprises 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; 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.;

[0144] In some embodiments, 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 least 97%, at least 98%, 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 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with 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 with 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 with SEQ ID NO: 20. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 containing the amino acid sequence of SEQ ID NO: 26; a CDR2 containing the amino acid sequence of SEQ ID NO: 27; and a CDR3 containing the amino acid sequence of SEQ ID NO: 28; VH3 comprises a CDR1 containing the amino acid sequence of SEQ ID NO: 18; a CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a CDR3 containing the amino acid sequence of SEQ ID NO: 20.;

[0145] In some embodiments, VL1 comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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;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 embodiments, 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; 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 comprises a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 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 DAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 32; 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 GAS); and a CDR3 comprising the amino acid sequence of SEQ ID NO: 24.;

[0146] In some embodiments, 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 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 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 16;VL2 comprises a CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 30; a CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 32; VL3 comprises a CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 22; a CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 24. In some preferred embodiments, VH1 comprises a CDR1 containing an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 containing an amino acid sequence having at least 90% identity with SEQ ID NO: 11;and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 16; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 32; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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 comprises 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; 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.;

[0147] In some embodiments, 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 with 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 with 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 with SEQ ID NO: 20. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 contains CDR1 including the amino acid sequence of SEQ ID NO: 10; CDR2 including the amino acid sequence of SEQ ID NO: 11; and CDR3 including the amino acid sequence of SEQ ID NO: 12; VH3 contains CDR1 including the amino acid sequence of SEQ ID NO: 18; CDR2 including the amino acid sequence of SEQ ID NO: 19; and CDR3 including the amino acid sequence of SEQ ID NO: 20.;

[0148] In some embodiments, 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;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 with 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 with 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 with SEQ ID NO: 24. In some preferred embodiments, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 16; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS);and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; 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.;

[0149] In some embodiments, 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 32;VL2 contains 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 with 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 with 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 with SEQ ID NO: 16; VL3 contains 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 with 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 with 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 with SEQ ID NO: 24. In some preferred embodiments, VH1 contains a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27;and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 16; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 comprises 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 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; 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.;

[0150] In some embodiments, 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 with 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 with 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 with SEQ ID NO: 12. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 contains CDR1 comprising the amino acid sequence of SEQ ID NO: 18; CDR2 comprising the amino acid sequence of SEQ ID NO: 19; and CDR3 comprising the amino acid sequence of SEQ ID NO: 20; VH3 contains CDR1 comprising the amino acid sequence of SEQ ID NO: 10; CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and CDR3 comprising the amino acid sequence of SEQ ID NO: 12.;

[0151] In some embodiments, VL1 comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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;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 with 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 with 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 with SEQ ID NO: 16. In some preferred embodiments, VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence of GTN);and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 CDR3 comprising the amino acid sequence of SEQ ID NO: 24; 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.;

[0152] In some embodiments, 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 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 with SEQ ID NO: 10; 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 with SEQ ID NO: 11; and 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 with SEQ ID NO: 12; VL1 comprises 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 with SEQ ID NO: 30; 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 with SEQ ID NO: 31 (having the sequence of DAS); and 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 with 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 with 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 with 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 with SEQ ID NO: 24; 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 with 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 with 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 with SEQ ID NO: 16. In some preferred embodiments, VH1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 26; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 27;and comprises a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 28; VH2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 18; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 19; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 20; VH3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 10; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 11; and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 12; VL1 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 31 (having the sequence of DAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 32; VL2 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 22; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 23 (having the sequence of GAS); and a CDR3 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 24; VL3 comprises a CDR1 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 14; a CDR2 comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 15 (having the sequence of GTN); and a CDR3 comprising an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 comprises 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 CDR3 comprising the amino acid sequence of SEQ ID NO: 24; 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.;

[0153] In some embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, VH3 comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 148. In some embodiments, VH3 comprises a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 149. In some embodiments, VH3 comprises a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 150. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, and VH3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, and VH3 comprises or consists of the corresponding amino acid sequence specified above.

[0154] In some embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, 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 embodiments, VL3 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 preferred embodiments, each of the CDR1, CDR2 and CDR3 of VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.

[0155] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) 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: 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) 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: 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0156] In some embodiments, 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; 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 with SEQ ID NO: 207. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0157] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 209; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 210; and a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 211; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 213; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0158] In some embodiments, 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 least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 219; 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0159] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0160] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0161] In some embodiments, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 241; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 242; and a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 243; VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 245; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical 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 with SEQ ID NO: 247. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0162] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 249; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 250; and a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 251; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 253; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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 with SEQ ID NO: 255. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0163] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0164] In some embodiments, 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; 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: 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0165] In some embodiments, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 273; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 274; and a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 275; VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 277; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to SEQ ID NO: 278 (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 with SEQ ID NO: 279. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0166] In some embodiments, 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; 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0167] In some embodiments, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprises a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 with SEQ ID NO: 295. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0168] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 297; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 298; and a CDR3 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 299; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 301; a CDR2 having an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical 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 with SEQ ID NO: 303. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the recited reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0169] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 321; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0170] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 with SEQ ID NO: 333. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity with the corresponding amino acid sequence specified above. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0171] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has at least 90% identity to 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 embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0172] In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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; VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, and VL3) comprise a CDR1 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at 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 with SEQ ID NO: 349. In some preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 has 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 with the described reference sequence. In some particularly preferred embodiments, each of the CDR1, CDR2 and CDR3 of VH1, VH2, VH3, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequence specified above.;

[0173] In some embodiments, VH1 comprises the same heavy chain variable region as VH3. In some embodiments, VL1 comprises the same light chain variable region as VL3. In some embodiments, VH1 comprises the same heavy chain variable region as VH3 and VL1 comprises the same light chain variable region as VL3.

[0174] In some embodiments, VH1 comprises the same heavy chain variable region as VH2. In some embodiments, VL1 comprises the same light chain variable region as VL2. In some embodiments, VH1 comprises the same heavy chain variable region as VH2 and VL1 comprises the same light chain variable region as VL2.

[0175] In some embodiments, VH2 comprises the same heavy chain variable region as VH3. In some embodiments, VL2 comprises the same light chain variable region as VL3. In some embodiments, VH2 comprises the same heavy chain variable region as VH3 and VL2 comprises the same light chain variable region as VL3.

[0176] In some embodiments, VH1, VH2, and VH3 each contain the same heavy chain variable region. In some embodiments, VL1, VL2, and VL3 each contain the same light chain variable region. In some embodiments, VH1, VH2, and VH3 each contain the same heavy chain variable region and VL1, VL2, and VL3 each contain the same light chain variable region.

[0177] In some embodiments, VH1, VH2, and VH3 each contain different heavy chain variable regions. In some embodiments, VL1, VL2, and VL3 each contain different light chain variable regions. In some embodiments, VH1, VH2, and VH3 each contain different heavy chain variable regions, and VL1, VL2, and VL3 each contain different light chain variable regions. In some embodiments, VH1, VH2, and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2, and VH3) have an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with 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. In some preferred embodiments, VH1, VH2, and VH3 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 with the described reference sequence. In some particularly preferred embodiments, VH1, VH2, and VH3 contain or consist of the corresponding amino acid sequences specified above.In some embodiments, VL1, VL2, and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2, 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 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 embodiments, VL1, VL2, and VL3 have at least 90% identity to 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 sequences. In some particularly preferred embodiments, VL1, VL2, and VL3 comprises or consists of the corresponding amino acid sequences specified above.In some embodiments, 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: 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; 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 embodiments, the sequence has, for example, at SEQ ID NO: 175, a mutation at N62, for example, N62Q or N62Q. In some preferred embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity to 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0178] In some embodiments, 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 with SEQ ID NO: 17; VL1, 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 with SEQ ID NO: 21. In some preferred embodiments, VH1, VH2, and VH3 each comprise an amino acid sequence having at least 90% identity with SEQ ID NO: 17; VL1, VL2, and VL3 each comprise an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, VH1, VH2, and VH3 each comprise the amino acid sequence of SEQ ID NO: 17; VL1, VL2, and VL3 each comprise the amino acid sequence of SEQ ID NO: 21.

[0179] In some embodiments, 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; 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 embodiments, 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; 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 embodiments, 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; VL2 comprises the amino acid sequence of SEQ ID NO: 29.

[0180] In some embodiments, 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 embodiments, 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 embodiments, 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; VL3 comprises the amino acid sequence of SEQ ID NO: 29.

[0181] In some embodiments, 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; 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. In some preferred embodiments, 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; 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 embodiments, 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; VL1 comprises the amino acid sequence of SEQ ID NO: 29.

[0182] In some embodiments, 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; 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 embodiments, VH1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 9; VH2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 25; VL1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 21; VL3 comprises an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; VL3 comprises the amino acid sequence of SEQ ID NO: 29.

[0183] In some embodiments, 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; 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 embodiments, VH1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 9; VH2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 25; VH3 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 13; VL2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 29; VL3 comprises an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; VL3 comprises the amino acid sequence of SEQ ID NO: 21.

[0184] In some embodiments, 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; 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 embodiments, VH1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 25; VH2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 9; VH3 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 17; VL1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 29; VL2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 13; VL3 comprises an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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 the amino acid sequence of SEQ ID NO: 29; VL2 comprises the amino acid sequence of SEQ ID NO: 13; VL3 comprises the amino acid sequence of SEQ ID NO: 21.

[0185] In some embodiments, 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 21; 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 with SEQ ID NO: 13.In some preferred embodiments, VH1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 25; VH2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 17; VH3 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 9; VL1 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 29; VL2 comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 21; VL3 comprises an amino acid sequence having at least 90% identity with 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 with the recited reference sequence. In some particularly preferred embodiments, 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; VL3 comprises the amino acid sequence of SEQ ID NO: 13.

[0186] In some embodiments, 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 with SEQ ID NO: 147. In some embodiments, 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 with SEQ ID NO: 147. In some embodiments, 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 with SEQ ID NO: 147. In some embodiments, 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 with SEQ ID NO: 151. In some embodiments, 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 with SEQ ID NO: 151. In some embodiments, 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 with SEQ ID NO: 151.In some preferred embodiments, 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 with the described reference sequences. In some particularly preferred embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0187] In some embodiments, VH1, VH2 and / or VH3 (VH1; VH2; VH3; VH1 and VH2; VH1 and VH3; VH2 and VH3; VH1, VH2 and VH3) comprise amino acid sequences having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 192; VL1, VL2 and / or VL3 (VL1; VL2; VL3; VL1 and VL2; VL1 and VL3; VL2 and VL3; VL1, VL2 and VL3) comprise amino acid sequences having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity with SEQ ID NO: 196. In some preferred embodiments, 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 with the described reference sequences. In some particularly preferred embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0188] In some embodiments, 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; 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity to 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0189] In some embodiments, 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; 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity to 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 comprise or consist of the corresponding amino acid sequences specified above.

[0190] In some embodiments, 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: 216; 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 embodiments, VH1, VH2, VH3, VL1, VL2, and VL3 have at least 90% identity to the corresponding amino acid sequences specified above. As used herein, "at least 90% identity" includes at least 91%, 92%, 93%, 94%, 95%,...

Claims

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

2. (a) VH1 includes the same heavy chain variable region as VH3, and VL1 includes the same light chain variable region as VL3; (b) VH1 includes the same heavy chain variable region as VH2, and VL1 includes the same light chain variable region as VL2; (c) VH2 includes the same heavy chain variable region as VH3, and VL2 includes the same light chain variable region as VL3; (d) VH1, VH2 and VH3 each include the same heavy chain variable region, and VL1, VL2 and VL3 each include the same light chain variable region; or (e) VH1, VH2 and VH3 each include different heavy chain variable regions, and VL1, VL2 and VL3 each include different light chain variable regions. The antigen-binding polypeptide complex according to claim 1.

3. (a) VH1, VH2 and VH3 each independently contain at least 80% of any one of sequence numbers 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 CDR1 containing an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity; 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, 2 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 with any one of 90, 298, 320, 328, 336, and 344; and 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 with any one of Sequence 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 contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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; CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 7 (SAS sequence) ), 15 (having a GTN sequence), 23 (having a GAS sequence), 31 (having a DAS sequence), and 39 (having a GAS sequence), 153, 157, 165 (having a GAS sequence), 173 (having a LGS sequence), 181, 198 (having a DAS sequence), 206 (having a DVS sequence), 214 (having an EDS sequence), 222 (having a KDS sequence), 230 (having a DAS sequence), 238 (having an AAS sequence), 246 (having a GAS sequence), 25 4 (having a DDS sequence), 262 (having a KDS sequence), 270 (having a SAS sequence), 278 (having a SAS sequence), 286 (having a GAS sequence), 294 (having a GAS sequence), 302 (having a GAS sequence), 324 (having a GAS sequence), 332 (having a DAS sequence), 340 (having a SAS sequence), and 348 (having a GAS sequence) and at least 80%, at least 85%, at least 90%, at least 95%, and at least 99% or CDR2 containing an amino acid sequence having 100% identity; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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; (b) VH1, VH2, and VH3 each include CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; and VL1, VL2, and VL3 each include: CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; (c) VH1 and VH3 each include CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VH2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VL1 and VL3 each include: CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; and VL2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

32. (d) VH1 and VH2 each include CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VH3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VL1 and VL2 each include: CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; and VL3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

32. (e) VH2 and VH3 each include CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VH1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VL2 and VL3 each include: CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; and VL1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

32. (f) VH1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 10; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 11; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 12; VH2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VH3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VL1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 14; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 15 (which has a GTN sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 16; VL2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; and VL3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

32. (g) VH1 comprises CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 10; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 11; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 12; VH2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VH3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VL1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 14; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 15 (which has a GTN sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 16; VL2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 32; and VL3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

24. (h) VH1 comprises CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VH2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 10; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 11; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 12; VH3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VL1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 32; VL2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 14; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 15 (which has a GTN sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 16; and VL3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

24. or (i) VH1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 26; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 27; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 28; VH2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 18; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 19; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 20; VH3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 10; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 11; and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 12; VL1 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 30; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 31 (which has the DAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 32; VL2 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 22; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 23 (which has a GAS sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 24; and VL3 includes CDR1 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 14; CDR2 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 15 (which has a GTN sequence); and CDR3 containing an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

16. The antigen-binding polypeptide complex according to claim 1.

4. The antigen-binding polypeptide complex according to claim 1, wherein VH1, VH2, and VH3 each independently contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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.

5. (a) VL1, VL2 and VL3 each independently contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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; (b) VH1, VH2, and VH3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 17; and VL1, VL2, and VL3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; (c) VH1 and VH3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 17; VH2 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 25; VL1 and VL3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; and VL2 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; (d) VH1 and VH2 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 17; VH3 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 25; VL1 and VL2 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; and VL3 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; (e) VH2 and VH3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 17; VH1 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 25; VL2 and VL3 each contain an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; and VL1 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; (f) 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 with 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 with 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 with SEQ ID NO: 25; VL1 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 13; VL2 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; and VL3 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; (g) 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 with 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 with 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 with SEQ ID NO: 17; VL1 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 13; VL2 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; and VL3 includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; (h) 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 with 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 with 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 with SEQ ID NO: 17; VL 1 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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 with 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 with SEQ ID NO: 21; or (i) 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 with 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 with 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 with SEQ ID NO: 9; VL1 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 29; VL2 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO: 21; and VL3 contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with SEQ ID NO:

13. The antigen-binding polypeptide complex according to claim 4.

6. The first polypeptide has a structure represented by VL1-L1-CL; The second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; The third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; The fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL, and The antigen-binding polypeptide complex according to claim 1, wherein the Fc region is a region comprising an immunoglobulin hinge including an upper hinge region, a central hinge region, a lower hinge region, or a combination thereof.

7. (a) Each linker L1 to L8 independently has a length of about 0 amino acids to about 50 amino acids; (b) Each linker L1 to L8 independently contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to any one of sequence numbers 46 to 80 (sequence number 47 has a G sequence, sequence number 48 has an A sequence, sequence number 49 has a GSS sequence, and sequence number 50 has an ASG sequence); (c) One or more of the linkers L1 to L8 are non-immunogenic; and / or (d) One or more of the linkers L1 to L8 do not contain consensus T cell epitopes. The antigen-binding polypeptide complex according to claim 1.

8. The first polypeptide has a structure represented by VL1-L1-CL; The second polypeptide has a structure represented by VH1-L2-CH1-L3-Fc; The third polypeptide has a structure represented by VH2-L4-VH3-L5-CH1-L6-Fc; The fourth polypeptide has a structure represented by VL3-L7-VL2-L8-CL, and The antigen-binding polypeptide complex according to claim 1, wherein the Fc region comprises at least one knob-into-hole modification or Fc effector function knockout mutation.

9. (a) The antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the knob-into-hole modification is based on the EU numbering scheme. (i) Replacement of knobs S354C and T366W, and replacement of holes Y349C, T366S, L368A, and Y407V; (ii) Hole replacement for M428L and N434S or N434A; (iii) Hole replacement for M252Y, S254T, and T256E; or (iv) combinations of those including; or (b) The antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the Fc effector function knockout mutation is L234A, L235A, P239A, or a combination thereof, based on the EU numbering scheme. The antigen-binding polypeptide complex according to claim 8.

10. The antigen-binding polypeptide complex according to claim 1, comprising a detectable label.

11. The antigen-binding polypeptide complex according to claim 10, wherein the detectable label is a radioactive label, a chemiluminescent label, a fluorescent label, an enzyme, a peptide tag, or a combination thereof.

12. The antigen-binding polypeptide complex according to claim 11, wherein the peptide tag is a polyhistidine tag consisting of about 4 to about 10 histidine residues.

13. The antigen-binding polypeptide complex according to claim 12, wherein the polyhistidine tag consists of approximately eight histidine residues.

14. Equilibrium dissociation constant (K) of approximately 10 μM to approximately 1 pM Ｄ The antigen-binding polypeptide complex according to claim 1, which specifically binds to the SARS-CoV-2 protein.

15. The aforementioned SARS-CoV-2 virus includes the original Wuhan strain (WA1), D614G spike protein variant (D614G), alpha variant (B.1.1.7), beta variant 1 (B.1.351.v1), gamma variant (P.1), delta variant (B.1.617.2 or AY.1), kappa variant (B.1.617.1), iota variant (B.1.526), ​​lambda variant (C.37), mu variant (B.1.621), and C. 1.2 variant, epsilon variant (B.1.427), or omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof, the antigen-binding polypeptide complex according to claim 1.

16. An antibody or its antigen-binding fragment comprising the antigen-binding polypeptide complex described in claim 1.

17. The antibody or its antigen-binding fragment according to claim 16, wherein the antibody is IgG, IgM, IgE, IgA, or IgD.

18. The antibody or antigen-binding fragment according to claim 17, wherein the IgG is IgG1, IgG2, IgG3, or IgG4.

19. The antigen-binding fragments are Fab, scFab, Fab', and F(ab'). ２ The antibody or antigen-binding fragment thereof according to claim 16, wherein the antibody is Fv or scFv.

20. The antibody is human or humanized; and / or The aforementioned antibody is a monoclonal antibody, a grafted antibody, or a chimeric antibody. The antibody or antigen-binding fragment according to claim 16.

21. It is a polyvalent anti-SARS-CoV2 antibody, (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody, and / or (ii) A combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as the aforementioned anti-SARS-CoV-2 polyvalent antibody. The anti-SARS-CoV-2 polyvalent antibody exhibits improved prevention of immune evasion compared to the aforementioned antibody.

22. A pharmaceutical composition comprising the antigen-binding polypeptide complex described in claim 1, or an antibody containing the antigen-binding polypeptide complex, or an antigen-binding fragment thereof.

23. A pharmaceutical composition comprising the antigen-binding polypeptide complex described in claim 1, or an antibody or antigen-binding fragment thereof containing the antigen-binding polypeptide complex, and an additional pharmaceutical agent.

24. A pharmaceutical composition comprising the antigen-binding polypeptide complex described in claim 1, or an antibody or antigen-binding fragment thereof containing the antigen-binding polypeptide complex, and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising the antigen-binding polypeptide complex described in claim 1 or an antibody or antigen-binding fragment thereof containing the antigen-binding polypeptide complex, an additional pharmaceutical agent, and a pharmaceutically acceptable carrier.

26. A pharmaceutical composition comprising the antibody described in claim 21.

27. A pharmaceutical composition comprising the antibody described in claim 21 and an additional pharmaceutical agent.

28. A pharmaceutical composition comprising the antibody described in claim 21 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising the antibody according to claim 21, an additional pharmaceutical agent, and a pharmaceutically acceptable carrier.

30. The pharmaceutical composition according to any one of claims 23, 25, 27, and 29, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, a vitamin D enhancer, an antiviral agent, an antimalarial agent, an antibiotic, or a combination thereof.

31. (a) The additional pharmaceutical agent is 25-hydroxyvitamin D; (b) The agent that enhances the vitamin D effect is a CYP24 inhibitor, a 1,25-dihydroxyvitamin D compound, or a combination thereof; or (c) The antiviral agent is an antiretroviral agent, an antibody against the SARS-CoV-2 virus, a reverse transcriptase inhibitor, or a combination thereof. The pharmaceutical composition according to claim 30.

32. The aforementioned antiviral agents include maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of acyclovir, ganciclovir, cidofovir, forcalnet, ribavirin, interferon alfa, PEG-modified interferon alfa, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peremivir, and valacyclovir. The pharmaceutical composition according to claim 30, which is penciclovir, valganciclovir, foscarnet, tenofovir, adefovir, entecavir, lamivudine, terbivudine, ribavirin, glecaprevir, grazoprevir, paritaprevir, simeprevir, boxylaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofobuvir, bebuterobimab, or a combination thereof.

33. The pharmaceutical composition according to claim 32, wherein the antiviral agent is bebuterobimab.

34. The aforementioned antiviral agents are Retrovir® (3'-azido-3'-deoxypyrimidine, zidovudine), 3'-azido-3'-deoxythymidine (AZT), HMD® (2',3'-dideoxycytidine, zalcitabine), VidexEC® (2',3'-dideoxyinosine, didanosine), Epivir® (lamivudine), and Zerit® (registered trademark). ) (Stabzine), Viread® (Tenofovir DF), Ziagen® (Abacavir), Emtriva® (Emtricitabine, FTC), Rescriber® (Delavirdin), Sustiva® (Efavirenz), Viramune® (Nevirapine, 11-Cyclopropyl-4-methyl-5,11-Dihydro-6H -Dipyrido[3,2-b:2′,3′-e][1,4]diazepine-6-one), trisodium phosphonoformate, ammonium-21-tungstenato-9-antimonate, 1-β-D-ribofuranoxyl-1,2,4-triazole-3-carboxamide, Aganerase® (amprenavir), Reyataz® (atazanavir), Lexiva® ( Fosanprenavir), Crixivan (registered trademark) (indinavir), Viracept (registered trademark) (nelfinavir), Norvir (registered trademark) (ritonavir), Fortovase (registered trademark) or Invirase (registered trademark) (saquinavir), Lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy-6-phenyl-2(R)(2,3,4-Trimethoxyphenylmethyl)-Hexanoyl-(L)-Valyl-N-(2-Methoxyethyl)-Amid), Adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011 BS (Palinavir), Polymannacetate, Fuzeon® (Enfuvirtide, T-20), Epzicom® (Abacavir and Lamivudine), Trizivir® (Abacavir, Lamivudine and Zidovudine), Truvada® (Emtricitabine and Tenofil DF), Combivir® (Lamivudine and Zidovudine), Kaletra® (Lopinavir and Ritonavir), or combinations thereof. The pharmaceutical composition according to claim 30.

35. (a) The antigen-binding polypeptide complex according to claim 1; (b) The antibody or antigen-binding fragment thereof according to claim 16 or 21; (c) (i) the antigen-binding polypeptide complex according to claim 1 or the antibody or antigen-binding fragment thereof according to claim 16 or 21, and (ii) additional pharmaceutical agents; (d) The pharmaceutical composition according to any one of claims 22 to 29; (e) (i) a pharmaceutical composition according to any one of claims 22 to 29, and (ii) additional pharmaceutical agents; (f) (i) a pharmaceutical composition according to any one of claims 22 to 29, and (ii) a pharmaceutical composition comprising an additional pharmaceutical agent; or (g) (i) a pharmaceutical composition according to any one of claims 22 to 29, and (ii) a pharmaceutical composition comprising an additional pharmaceutical agent and a pharmaceutically acceptable carrier; A kit that includes this.

36. The kit according to claim 35, further comprising instructions for use.

37. A pharmaceutical composition for preventing or treating SARS-CoV-2 virus infection or coronavirus disease 2019 (COVID-19) in a subject in need, comprising an effective amount of the antigen-binding polypeptide complex described in claim 1 or an antibody containing the antigen-binding polypeptide complex or an antigen-binding fragment thereof.

38. A pharmaceutical composition for preventing or treating SARS-CoV-2 virus infection or coronavirus disease 2019 (COVID-19) in a subject in need thereof, comprising an effective amount of the antibody described in claim 21.

39. An in vitro or ex vivo method for assisting in the diagnosis of SARS-CoV-2 virus infection, (i) A step of contacting a sample obtained from a subject with the antigen-binding polypeptide complex described in claim 1 or an antibody containing the antigen-binding polypeptide complex or an antigen-binding fragment thereof; and (ii) A step of detecting the presence or absence of the polypeptide complex, antibody or fragment, and a viral complex containing the SARS-CoV-2 virus, its virion or fragment. Includes, The method, wherein, if the aforementioned virus complex is detected, its presence indicates that the subject is infected with the SARS-CoV-2 virus, or is suspected to be infected with the SARS-CoV-2 virus.

40. An in vitro or ex vivo method for assisting in the diagnosis of SARS-CoV-2 virus infection, (i) A step of contacting a sample obtained from a subject with the antigen-binding polypeptide complex described in claim 1 or an antibody containing the antigen-binding polypeptide complex or an antigen-binding fragment thereof; and (ii) A step of detecting the presence or absence of the polypeptide complex, antibody or fragment, and a viral complex containing the SARS-CoV-2 virus, its virion or fragment. Includes, The method wherein, if the aforementioned virus complex is not detected, its absence indicates that the subject is not infected with the SARS-CoV-2 virus, or is not suspected of being infected with the SARS-CoV-2 virus.

41. An in vitro or ex vivo method for assisting in the diagnosis of COVID-19, (i) A step of contacting a sample obtained from a subject with the antigen-binding polypeptide complex described in claim 1 or an antibody containing the antigen-binding polypeptide complex or an antigen-binding fragment thereof; and (ii) A step of detecting the presence or absence of the polypeptide complex, antibody or fragment, and a viral complex containing the SARS-CoV-2 virus, its virion or fragment. Includes, The method wherein, if the aforementioned virus complex is detected, its presence indicates that the subject has COVID-19 or is suspected of having COVID-19.

42. An in vitro or ex vivo method for assisting in the diagnosis of COVID-19, (i) A step of contacting a sample obtained from a subject with the antigen-binding polypeptide complex described in claim 1 or an antibody containing the antigen-binding polypeptide complex or an antigen-binding fragment thereof; and (ii) A step of detecting the presence or absence of the polypeptide complex, antibody or fragment, and a viral complex containing the SARS-CoV-2 virus, its virion or fragment. Includes, The method wherein, if the virus complex is not detected, its absence indicates that the subject does not have COVID-19 or is not suspected of having COVID-19.

43. (a) The sample is a nasal swab, a tissue sample, saliva, plasma or blood; and / or (b) Detection of the presence or absence of the viral complex includes enzyme-linked immunosorbent assay (ELISA), immunospot assay, lateral flow assay, flow cytometry, immunohistochemistry, or Western blotting. The method according to any one of claims 39 to 42.

44. The aforementioned SARS-CoV-2 virus includes the original Wuhan strain (WA1), D614G spike protein variant (D614G), alpha variant (B.1.1.7), beta variant 1 (B.1.351.v1), gamma variant (P.1), 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), and C. 1.2 variant, omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof, the pharmaceutical composition according to claim 37 or 38.

45. The aforementioned SARS-CoV-2 virus includes the original Wuhan strain (WA1), D614G spike protein variant (D614G), alpha variant (B.1.1.7), beta variant 1 (B.1.351.v1), gamma variant (P.1), 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), and C. The method according to any one of claims 39 to 42, wherein the variant is 1.2, the Omicron variant (BA1.1.529, BA.1, BA.2, BA.2.12.1, BA.4, BA.4 / 5, BA.5, BQ.1, BQ.1.1, BA.2.75, BA.2.75.2, BA.4.6, BQ.1.1, BJ.1, XBB, XBB1.5, BF.7, or CH.1.1), or a combination thereof.

46. A pharmaceutical composition for preventing immune evasion of the SARS-CoV-2 virus in subjects infected with the SARS-CoV-2 virus, (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody, and / or (ii) A combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as the aforementioned anti-SARS-CoV-2 polyvalent antibody. The pharmaceutical composition comprising an effective amount of the anti-SARS-CoV2 polyvalent antibody, which exhibits improved prevention of immune evasion compared to the above.

47. A pharmaceutical composition for increasing the neutralizing efficacy against the SARS-CoV-2 virus in subjects infected with the SARS-CoV-2 virus, (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody, and / or (ii) A combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as the aforementioned anti-SARS-CoV-2 polyvalent antibody. The pharmaceutical composition comprising an effective amount of the anti-SARS-CoV2 polyvalent antibody exhibiting increased neutralizing efficacy compared to the above.

48. (a) The anti-SARS-CoV2 polyvalent antibody exhibits improved prevention of immune evasion compared to a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody; (b) The anti-SARS-CoV2 polyvalent antibody exhibits increased neutralizing efficacy compared to a combination of monovalent anti-SARS-CoV2 antibodies that bind to the same antigen as the anti-SARS-CoV2 polyvalent antibody. (c) The anti-SARS-CoV2 polyvalent antibody prevents immunization evasion of the anti-SARS-CoV2 polyvalent antibody for at least two, at least three, at least four, at least five, at least six, or at least seven selected rounds when measured by an antibody evasion assay; (d) The anti-SARS-CoV2 polyvalent antibody prevents immunization evasion of the anti-SARS-CoV2 polyvalent antibody after at least two, at least three, at least four, at least five, at least six, or at least seven exposures of the subject to the SARS-CoV2 virus; and / or (e) The anti-SARS-CoV2 polyvalent antibody is (i) a monovalent anti-SARS-CoV2 antibody that binds to one of the same antigens as the anti-SARS-CoV2 polyvalent antibody, and / or (ii) A combination of monovalent anti-SARS-CoV-2 antibodies that bind to the same antigen as the aforementioned anti-SARS-CoV-2 polyvalent antibody. Compared to the above, it is at least 100 times, at least 500 times, at least 1,000 times, or at least 2,000 times more effective in inhibiting the growth of the SARS-CoV2 virus. The pharmaceutical composition according to claim 46 or 47.

49. The pharmaceutical composition according to claim 46 or 47, wherein the anti-SARS-CoV-2 polyvalent antibody comprises a first antigen-binding site that specifically binds to the SARS-CoV-2 protein and a second antigen-binding site that specifically binds to the SARS-CoV-2 protein.

50. The pharmaceutical composition according to claim 49, wherein the first antigen-binding site is different from the second antigen-binding site.

51. The pharmaceutical composition according to claim 49, wherein the first antigen-binding site comprises a first heavy chain variable region and a first light chain variable region, and the second antigen-binding site comprises a second heavy chain variable region and a second light chain variable region.

52. The pharmaceutical composition according to claim 51, wherein the first and second heavy chain variable regions each include CDR1, CDR2, and CDR3 regions, and the first and second light chain variable regions each include CDR1, CDR2, and CDR3 regions.

53. 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 with 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 with 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 with 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 with 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 in the first light chain variable region is sequence numbers 7 (having a sequence of SAS), 15 (having a sequence of GTN), 23 (having a sequence of GAS), 31 (having a sequence of DAS), and 39 (having a sequence of GAS), 153, 157, 165 (having a sequence of GAS), 173 (having a sequence of LGS), 181, 198 (having a sequence of DAS), 206 (having a sequence of DVS), 214 (having a sequence of EDS), 222 (having a sequence of KDS), 230 (having a sequence of DAS), 238 (having a sequence of AAS), and 246 (having a sequence of GAS). ), comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of the following: 254 (having a DDS sequence), 262 (having a KDS sequence), 270 (having a SAS sequence), 278 (having a SAS sequence), 286 (having a GAS sequence), 294 (having a GAS sequence), 302 (having a GAS sequence), 324 (having a GAS sequence), 332 (having a DAS sequence), 340 (having a SAS sequence), and 348 (having a GAS sequence); 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 with 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 with 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 with 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 with 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 with 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 in the second light chain variable region is sequence numbers 7 (having a sequence of SAS), 15 (having a sequence of GTN), 23 (having a sequence of GAS), 31 (having a sequence of DAS), and 39 (having a sequence of GAS), 153, 157, 165 (having a sequence of GAS), 173 (having a sequence of LGS), 181, 198 (having a sequence of DAS), 206 (having a sequence of DVS), 214 (having a sequence of EDS), 222 (having a sequence of KDS), 230 (having a sequence of DAS), 238 (having a sequence of AAS), and 246 (having a sequence of GAS). , comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of 254 (having a DDS sequence), 262 (having a KDS sequence), 270 (having a SAS sequence), 278 (having a SAS sequence), 286 (having a GAS sequence), 294 (having a GAS sequence), 302 (having a GAS sequence), 324 (having a GAS sequence), 332 (having a DAS sequence), 340 (having a SAS sequence), and 348 (having a GAS sequence); and The CDR3 of the second light chain variable region contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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 pharmaceutical composition according to claim 52.

54. The first heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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 region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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 region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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; and The second light chain variable region includes an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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 pharmaceutical composition according to claim 51.

55. The pharmaceutical composition according to claim 49, wherein the anti-SARS-CoV2 polyvalent antibody further comprises a third antigen-binding site.

56. The pharmaceutical composition according to claim 55, wherein the third antigen-binding site is different from the first antigen-binding site, different from the second antigen-binding site, or different from both the first and second antigen-binding sites.

57. The pharmaceutical composition according to claim 55, wherein the third antigen-binding site includes a third heavy chain variable region and a third light chain variable region.

58. The third heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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; and the The pharmaceutical composition according to claim 57, wherein the light chain variable region of 3 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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.

59. The pharmaceutical composition according to claim 57, wherein the third heavy chain variable region includes CDR1, CDR2, and CDR3 regions.

60. 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 with 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 with 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 with 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 with 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 in the third light chain variable region is sequence numbers 7 (having a sequence of SAS), 15 (having a sequence of GTN), 23 (having a sequence of GAS), 31 (having a sequence of DAS), and 39 (having a sequence of GAS), 153, 157, 165 (having a sequence of GAS), 173 (having a sequence of LGS), 181, 198 (having a sequence of DAS), 206 (having a sequence of DVS), 214 (having a sequence of EDS), 222 (having a sequence of KDS), 230 (having a sequence of DAS), 238 (having a sequence of AAS), and 246 (having a sequence of GAS). , comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of 254 (having a DDS sequence), 262 (having a KDS sequence), 270 (having a SAS sequence), 278 (having a SAS sequence), 286 (having a GAS sequence), 294 (having a GAS sequence), 302 (having a GAS sequence), 324 (having a GAS sequence), 332 (having a DAS sequence), 340 (having a SAS sequence), and 348 (having a GAS sequence); and The CDR3 of the third light chain variable region contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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 pharmaceutical composition according to claim 59.

61. The pharmaceutical composition according to claim 55, wherein the anti-SARS-CoV2 polyvalent antibody further comprises a fourth antigen-binding site.

62. The fourth antigen-binding site is different from one or more of the first, second, and third antigen-binding sites, or The first, second, third, and fourth antigen-binding sites are different. The pharmaceutical composition according to claim 61.

63. The pharmaceutical composition according to claim 61, wherein the fourth antigen-binding site includes a fourth heavy chain variable region and a fourth light chain variable region.

64. The fourth heavy chain variable region comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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; and the The pharmaceutical composition according to claim 63, wherein the light chain variable region of 4 comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity with 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.

65. The pharmaceutical composition according to claim 63, wherein the fourth heavy chain variable region includes CDR1, CDR2, and CDR3 regions.

66. 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 with 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 with 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 with 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 with 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 in the fourth light chain variable region is sequence numbers 7 (having a sequence of SAS), 15 (having a sequence of GTN), 23 (having a sequence of GAS), 31 (having a sequence of DAS), and 39 (having a sequence of GAS), 153, 157, 165 (having a sequence of GAS), 173 (having a sequence of LGS), 181, 198 (having a sequence of DAS), 206 (having a sequence of DVS), 214 (having a sequence of EDS), 222 (having a sequence of KDS), 230 (having a sequence of DAS), 238 (having a sequence of AAS), and 246 (having a sequence of GAS). , comprising an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with any one of 254 (having a DDS sequence), 262 (having a KDS sequence), 270 (having a SAS sequence), 278 (having a SAS sequence), 286 (having a GAS sequence), 294 (having a GAS sequence), 302 (having a GAS sequence), 324 (having a GAS sequence), 332 (having a DAS sequence), 340 (having a SAS sequence), and 348 (having a GAS sequence); and The CDR3 of the fourth light chain variable region contains an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identity with 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. The pharmaceutical composition according to claim 65.

67. The pharmaceutical composition according to claim 46 or 47, wherein the anti-SARS-CoV2 polyvalent antibody is the antibody or antigen-binding fragment according to claim 16 or 21.

68. The pharmaceutical composition according to claim 46 or 47, wherein the antigen is the SARS-CoV-2 protein.

69. The pharmaceutical composition according to claim 46 or 47, wherein the SARS-CoV-2 virus is a SARS-CoV-2 variant.

70. The pharmaceutical composition according to claim 69, wherein the SARS-CoV2 variant is an alpha variant (B.1.1.7), a beta variant (B.1.351), a gamma variant (P.1), a delta variant, an epsilon variant (B.1.427), or an omicron variant (B.1.1.529), or a combination thereof.

71. The pharmaceutical composition according to claim 70, wherein the omicron variant is BA. 1, BA. 2, BA. 2.12.1, BA. 4, BA. 4 / 5, BA. 5, BQ. 1, BQ. 1.1, BA. 2.75, BA. 2.75.2, BA. 4.6, BQ. 1.1, BJ. 1, XBB, XBB1.5, BF. 7, CH. 1.1, or a combination thereof.

72. (a) an effective amount of an additional pharmaceutical agent; or (b) an effective amount of a pharmaceutical composition comprising (i) an additional pharmaceutical agent and (ii) a pharmaceutically acceptable carrier. A pharmaceutical composition according to any one of claims 37, 38, 46, and 47, used in combination with the above.

73. The pharmaceutical composition according to claim 72, wherein the additional pharmaceutical agent is 25-hydroxyvitamin D, a vitamin D enhancer, an antiviral agent, an antimalarial agent, an antibiotic, or a combination thereof.

74. (a) The additional pharmaceutical agent is 25-hydroxyvitamin D; (b) The agent that enhances the vitamin D effect is a CYP24 inhibitor, a 1,25-dihydroxyvitamin D compound, or a combination thereof; or (c) The antiviral agent is an antiretroviral agent, an antibody against the SARS-CoV-2 virus, a reverse transcriptase inhibitor, or a combination thereof. The pharmaceutical composition according to claim 73.

75. The aforementioned antiviral agents include maraviroc, enfuvirtide, amantadine, lamivudine, nevirapine, efavirenz, dolutegravir, elvitegravir, raltegravir, acyclovir and any nucleoside analog of acyclovir, ganciclovir, cidofovir, forcalnet, ribavirin, interferon alfa, PEG-modified interferon alfa, boceprevir, atazanavir, darunavir, indinavir, oseltamivir, zanamivir, rimantadine, peremivir, and valacyclovir. The pharmaceutical composition according to claim 73, which is penciclovir, valganciclovir, foscarnet, tenofovir, adefovir, entecavir, lamivudine, terbivudine, ribavirin, glecaprevir, grazoprevir, paritaprevir, simeprevir, boxilaprevir, daclatasvir, elbasvir, ledipasvir, ombitasvir, pibrentasvir, velpatasvir, dasabuvir, famciclovir, remdesivir, trifluridine, sofobuvir, bebuterobimab, or a combination thereof.

76. The pharmaceutical composition according to claim 75, wherein the antiviral agent is bebuterobimab.

77. The aforementioned antiviral agents are Retrovir® (3'-azido-3'-deoxypyrimidine, zidovudine), 3'-azido-3'-deoxythymidine (AZT), HMD® (2',3'-dideoxycytidine, zalcitabine), VidexEC® (2',3'-dideoxyinosine, didanosine), Epivir® (lamivudine), and Zerit® (registered trademark). ) (Stabzine), Viread® (Tenofovir DF), Ziagen® (Abacavir), Emtriva® (Emtricitabine, FTC), Rescriber® (Delavirdin), Sustiva® (Efavirenz), Viramune® (Nevirapine, 11-Cyclopropyl-4-methyl-5,11-Dihydro-6H -Dipyrido[3,2-b:2′,3′-e][1,4]diazepine-6-one), trisodium phosphonoformate, ammonium-21-tungstenato-9-antimonate, 1-β-D-ribofuranoxyl-1,2,4-triazole-3-carboxamide, Aganerase® (amprenavir), Reyataz® (atazanavir), Lexiva® ( Fosanprenavir), Crixivan (registered trademark) (indinavir), Viracept (registered trademark) (nelfinavir), Norvir (registered trademark) (ritonavir), Fortovase (registered trademark) or Invirase (registered trademark) (saquinavir), Lasinavir (5(S)-(tert-butoxycarbonylamino)-4(S)-hydroxy-6-phenyl-2(R)(2,3,4-Trimethoxyphenylmethyl)-Hexanoyl-(L)-Valyl-N-(2-Methoxyethyl)-Amid), Adriamycin, KVX-478, VX-478, 141W94, AG-1343, KNI-272, U-96988, BILA-2011 The pharmaceutical composition according to claim 73, which is BS (palinavir), polymannoacetate, Fuzeon® (enfuvirtide, T-20), Epzicom® (abacavir and lamivudine), Trizivir® (abacavir, lamivudine and zidovudine), Truvada® (emtricitabine and tenofil DF), Combivir® (lamivudine and zidovudine), Kaletra® (lopinavir and ritonavir), or a combination thereof.

78. (a) The additional pharmaceutical agent is administered before the antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof; (b) The additional pharmaceutical agent is administered after the antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof; (c) The additional pharmaceutical agent is administered simultaneously with the antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof; (d) The additional pharmaceutical agent and the antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof are administered in the same pharmaceutical composition; or (e) The additional pharmaceutical agents and the antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof are administered in different pharmaceutical compositions. The pharmaceutical composition according to claim 72.

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