WO2023156409A1 - Methods of treating blood disorders with vwf-targeted monospecific antibodies - Google Patents
Methods of treating blood disorders with vwf-targeted monospecific antibodies Download PDFInfo
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- WO2023156409A1 WO2023156409A1 PCT/EP2023/053681 EP2023053681W WO2023156409A1 WO 2023156409 A1 WO2023156409 A1 WO 2023156409A1 EP 2023053681 W EP2023053681 W EP 2023053681W WO 2023156409 A1 WO2023156409 A1 WO 2023156409A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/36—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Definitions
- VWF von Willebrand factor
- monospecific antibodies comprising an antigen-binding site that specifically binds to an epitope of a von Willebrand Factor (VWF) protein positioned at a cysteine knot (CK) domain and a fragment crystallizable (Fc) region, wherein binding of an antibody disclosed herein to the VWF protein results in accumulation of the VWF protein in blood plasma as compared to a blood plasma level of the VWF protein in the absence of the antibody.
- VWF von Willebrand Factor
- CK cysteine knot
- Fc fragment crystallizable
- an antibody disclosed herein is a monovalent antibody.
- the Fc region is a wild-type Fc region.
- the Fc region is a modified Fc region.
- the modified Fc region comprises one or more mutations selected from the group consisting of a R435H mutation, N434A mutation, T252L/T253S/T254F mutation, E294delta/T307P/N434Y mutation, T256N/A378V/S383N/N434Y mutation, E294 delta mutation, M252Y/S254T/T256E mutation, M428L/N434S mutation, T307A/E380A/N434A mutation, T250Q/M428L mutation, T250Q/M428F mutation, T250E/M428F mutation, T250E/M428L mutation, T256D/Q311V/A378V mutation, T256D/H286D/T307R/Q311 V/A378V mutation, H285N/T307Q/N315D mutation, T307Q/Q311V/A378V mutation, H285D/T307Q/
- the Fc region comprises an N-terminal truncation (e.g., a truncation by 1, 2, 3, 4, 5, 6, 7, 8 ,9 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,
- the antibody is a human IgG4 antibody comprising a first heavy chain and a second heavy chain.
- the first heavy chain comprises a S228P/T366W7F234A/L235A/delta-K447 mutation and the second heavy chain comprises a S228P/T366S/L368A/Y407V/F234A/L235A/delta-K447 mutation.
- the first heavy chain comprises a S228P/T366W/delta-K447 mutation and the second heavy chain comprises a S228P/T366S/L368A/Y407V/delta-K447 mutation.
- the first heavy chain and the second heavy chain further comprise a M252Y/S254T/T256E mutation.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 453, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 473, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 454, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 474, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 455, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 475, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 456, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 476, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 457, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 477, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 79.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 86.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 93.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 458, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 478, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 100.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 107.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 114.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 459, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 479, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 121.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 128.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 135.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 142.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 149.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 156.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 163.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 170.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 177.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 184.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 191.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 198.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 205.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 212.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 219.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 226.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 233.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 240.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 247.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 460, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 480, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 250 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 254.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 250 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 254.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 250 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 254.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 250 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 254.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 250 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 254.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 255, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 256.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 250 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 251, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 252, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 253; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 257 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 261.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 257 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 261.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 257 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 261.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 257 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 261.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 257 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 261.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 262, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 263.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 257 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 258, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 259, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 260; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 264 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 268.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 264 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 268.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 264 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 268.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 264 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 268.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 264 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 268.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 269, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAV, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 270.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 264 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 265, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 266, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 267; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 271 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 275.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 271 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 275.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 271 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 275.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 271 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 275.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 276, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 277.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 271 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 272, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 273, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 274; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 278 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 282.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 278 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 282.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 278 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 282.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 278 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 282.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 278 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 282.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 283, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 284.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 278 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 279, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 280, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 281; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 285 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 289.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 285 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 289.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 285 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 289.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 285 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 289.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 285 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 289.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 290, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 291.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 285 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 286, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 287, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 288; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 292 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 296.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 292 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 296.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 292 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 296.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 292 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 296.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 292 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 296.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 297, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 298.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 292 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 293, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 294, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 295; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 299 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 303.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 299 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 303.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 299 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 303.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 299 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 303.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 299 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 303.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 304, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 305.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 299 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 300, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 301, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 302; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 306 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 310.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 306 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 310.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 306 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 310.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 306 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 310.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 306 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 310.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 306 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 307, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 308, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 309
- VH variable heavy chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 461, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 481, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 313 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 317.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 313 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 317.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 313 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 317.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 313 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 317.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 313 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 317.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 318, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 319.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 313 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 314, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 315, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 316; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 320 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 324.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 320 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 324.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 320 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 324.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 320 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 324.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 320 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 324.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 323; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 320 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 321, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 322, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 3
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 327 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 331.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 327 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 331.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 327 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 331.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 327 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 331.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 327 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 331.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 332, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 333.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 327 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 328, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 329, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 330; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 334 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 338.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 334 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 338.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 334 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 338.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 334 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 338.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 334 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 338.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 337; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 334 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 335, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 336, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 341 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 345.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 341 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 345.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 341 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 345.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 341 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 345.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 341 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 345.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 346, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 347.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 341 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 342, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 343, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 344; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 348 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 352.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 348 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 352.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 348 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 352.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 348 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 352.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 348 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 352.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 353, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DTA, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 354.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 348 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 349, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 350, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 351; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 355 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 359.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 355 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 359.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 355 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 359.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 355 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 359.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 355 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 359.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 360, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 361.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 355 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 356, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 357, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 358; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 362 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 366.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 362 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 366.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 362 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 366.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 362 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 366.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 362 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 366.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 367, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 368.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 362 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 363, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 364, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 365; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 369 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 373.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 369 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 373.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 369 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 373.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 369 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 373.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 369 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 373.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 374, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GTS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 375.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 369 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 370, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 371, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 372; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 376 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 380.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 376 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 380.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 376 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 380.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 376 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 380.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 376 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 380.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 381, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ETS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 382.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 376 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 377, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 378, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 379; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 383 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 387.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 383 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 387.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 383 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 387.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 383 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 387.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 383 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 387.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 388, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 389.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 383 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 384, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 385, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 386; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 390 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 394.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 390 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 394.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 390 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 394.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 390 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 394.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 390 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 394.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 393; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 390 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 391, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 392, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 3
- VH variable heavy chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 462, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 482, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 397 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 401.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 397 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 401.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 397 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 401.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 397 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 401.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 397 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 401.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 402, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 403.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 397 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 398, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 399, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 400; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 404 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 408.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 404 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 408.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 404 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 408.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 404 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 408.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 404 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 408.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 407; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 404 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 405, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 406, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 40
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 411 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 415.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 411 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 415.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 411 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 415.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 411 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 415.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 411 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 415.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 416, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 417.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 411 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 412, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 413, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 414; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 418 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 422.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 418 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 422.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 418 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 422.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 418 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 422.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 418 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 422.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 421; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO:
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 418 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 419, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 420, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 425 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 429.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 425 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 429.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 425 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 429.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 425 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 429.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 425 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 429.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 430, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 431.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 425 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 426, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 427, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 428; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 432 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 436.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 432 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 436.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 432 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 436.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 432 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 436.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 432 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 436.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 437, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 438.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 432 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 433, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 434, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 435; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VL
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 439 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 443.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 439 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 443.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 439 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 443.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 439 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 443.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 439 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 443.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 444, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 445.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 439 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 440, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 441, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 442; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 8
- VH
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: SEQ 446 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 450.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 446 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 450.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 446 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 450.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 446 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 450.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 446 and a variable light chain (VL) region having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 450.
- the antibody comprises a VH comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449; and a VL comprising therein a complementarity determining region (CDR) LI having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 451, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DNF, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 452.
- CDR complementarity determining region
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 446 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 447, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 448, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 449; a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody binds to one or more amino acid residues of the VWF CK domain selected from D2726, R2730, K2735, E2744, D2746, K2757, D2763, and T2789. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, R2730, D2746, and K2757. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, and D2746. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, D2746, and K2757.
- the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, D2746, and K2757. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735, E2744, D2746, and D2763. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: R2730, K2735, E2744, D2746, K2757, and D2763. In some embodiments, the antibody binds to at least amino acid residue K2735 of the VWF CK domain.
- the antibody binds to at least the following amino acid residues of the VWF CK domain: D2726, K2735, and K2757. In some embodiments, the antibody binds to at least the following amino acid residues of the VWF CK domain: K2735 and D2763. In some embodiments, the modified Fc region increases the blood plasma halflife of the antibody as compared to a blood plasma half-life of an antibody lacking modifications in the Fc region.
- the modified Fc region increases the blood plasma half-life of an antibody disclosed herein by at least 1.5-fold, 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold greater as compared to a blood plasma half-life of an antibody lacking modifications in the Fc region.
- the modified Fc region increases the blood plasma half-life of an antibody disclosed herein by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, 10,000%, or greater as compared to a blood plasma half-life of an antibody lacking modifications in the Fc region.
- the modified Fc region reduces one or more effector functions of an antibody disclosed herein as compared to the effector functions of an antibody lacking modifications in the Fc region.
- the one or more effector functions are selected from the group consisting of antibody-dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), opsonization, phagocytosis, transcytosis, neutralization of infectivity, inflammation, mucosal immunity, and neonatal immunity.
- the modified Fc region reduces one or more effector functions of an antibody disclosed herein by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% as compared to the one or more effector functions of the antibody lacking modifications in the Fc region.
- the modified Fc region reduces one or more effector functions of an antibody disclosed herein by at least 1.5-fold, 2-fold, 3-fold, 4- fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold as compared to the one or more effector functions of the antibody lacking modifications in the Fc region.
- binding of an antibody disclosed herein to the VWF protein does not result in a change in function of the VWF protein.
- binding of an antibody disclosed herein to VWF does not inhibit VWF protein binding to one or more binding partners.
- the one or more binding partners are selected from the group consisting of Factor VIII (FVIII), collagen, glycoprotein lb (gp lb), glycoprotein Ilb/IIIa (gpIIb/IIIa), and ADAM Metallopeptidase With Thrombospondin Type 1 Motif 13 (ADAMTS13).
- binding of an antibody disclosed herein does not inhibit binding of the VWF protein to platelet cells.
- the accumulation of the VWF protein in blood plasma results in a blood plasma level of the VWF protein that is at least 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9- fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold greater as compared to a blood plasma level of the VWF protein in the absence of the antibody.
- the accumulation of the VWF protein in blood plasma results in a blood plasma level of the VWF protein that is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, 10,000%, or greater as compared to a blood plasma level of the VWF protein in the absence of the antibody.
- binding of an antibody disclosed herein to VWF in blood plasma increases a blood plasma half-life of the VWF protein as compared to a blood plasma half-life of the VWF protein in the absence of the antibody. In some embodiments, binding of an antibody disclosed herein to VWF in blood plasma increases the blood plasma half-life of the VWF protein by at least 1.5- fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13- fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold as compared to the blood plasma half-life of the VWF protein in the absence of the antibody.
- binding of an antibody disclosed herein to VWF in blood plasma increases the blood plasma half-life of the VWF protein by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, or 10,000% as compared to the blood plasma half-life of the VWF protein in the absence of the antibody.
- binding of an antibody disclosed herein to the VWF protein in blood plasma results in accumulation of a FVIII protein in blood plasma as compared to a blood plasma level of a FVIII protein in the absence of the antibody.
- the accumulation of the FVIII protein in blood plasma results in a blood plasma level of the FVIII protein that is at least 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold greater as compared to a blood plasma level of the FVIII protein in the absence of the antibody.
- the accumulation of the FVIII protein in blood plasma results in a blood plasma level of the FVIII protein that is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, 10,000%, or greater as compared to the blood plasma level of a FVIII protein in the absence of the antibody.
- binding of an antibody disclosed herein to VWF in blood plasma increases a blood plasma half-life of FVIII protein as compared to a blood plasma half-life of the FVIII protein in the absence of the antibody. In some embodiments, binding of an antibody disclosed herein to VWF in blood plasma increases the blood plasma half-life of the FVIII protein by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17- fold, 18-fold, 19-fold, or 20-fold as compared to the blood plasma half-life of the FVIII protein in the absence of the antibody.
- binding of an antibody disclosed herein to VWF in blood plasma increases the blood plasma half-life of the FVIII protein by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, or 10,000% as compared to the blood plasma half-life of the FVIII protein in the absence of the antibody.
- an antibody disclosed herein binds specifically to a VWF homodimer comprising two VWF monomers linked tail-to-tail via CK-domain joining in a 1 : 1 stoichiometry. In some embodiments, an antibody disclosed herein binds specifically to a VWF homodimer comprising two VWF monomers linked tail-to-tail via CK domain joining in 2: 1 stoichiometry.
- an antibody disclosed herein binds to the CK domain of the VWF protein with a dissociation constant (Ka) of less than 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 7 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 0.5 nM, 0.25 nM, 0.1 nM, 0.075 nM, 0.05 nM, 0.025 nM, 0.01 nM, or less.
- Ka dissociation constant
- an antibody disclosed herein is cross-reactive with a VWF protein of Macaca fascicularis, Mus muscuhis. and/or Canis familiaris.
- an antibody disclosed herein has an affinity with a VWF protein of Macaca fascicularis. Mus muscuhis. and/or Canis familiaris that is at most 10-fold (e.g., at most 10-fold, 9-fold, 8-fold, 7-fold, 6- fold, 5-fold, 4-fold, 3-fold, 2-fold, 1.5-fold, or less) lower than an affinity of the antibody to a human VWF protein.
- an antibody disclosed herein is a human antibody, humanized antibody, or chimeric antibody.
- the CK domain is positioned between amino acid positions 2,723 and 2,813 of SEQ ID NO: 1.
- the CK domain is a CK domain of a human VWF protein having at least 85% sequence identity (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) to the amino acid sequence of any one of SEQ ID NOs: 5, 6, 486, or 487.
- the CK domain has an amino acid sequence of SEQ ID NO: 5.
- the CK domain is a CK domain of a non-human primate (NHP) VWF protein having at least 85% sequence identity (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) to the amino acid sequence of SEQ ID NO: 6.
- the CK domain has an amino acid sequence of SEQ ID NO: 6.
- a complex comprising a VWF protein and a monospecific antibody of the foregoing aspects and embodiments.
- the complex comprises a VWF monomer.
- the complex comprises a VWF dimer.
- the complex comprises a VWF multimer.
- the multimer has a molecular weight of at least 250 kDa (e.g., at least 250 kDa, 500 kDa, 750 kDa, 1000 kDa, 1,250 kDa, 1,500 kDa, 1,750 kDa, 2,000 kDa, 3,000 kDa, 4,000 kDa, 5,000 kDa, 6,000 kDa, 7,000 kDa, 8,000 kDa, 9,000 kDa, 10,000 kDa, 11,000 kDa, 12,000 kDa, 13,000 kDa, 14,000 kDa, 15,000 kDa, 16,000 kDa, 17,000 kDa, 18,000 kDa, 19,000 kDa, 20,000 kDa, 21,000 kDa, 22,000 kDa, 23,000 kDa, 24,000 kDa, 25,000 kDa, or more).
- kDa e.g.,
- compositions comprising a monospecific antibody of the foregoing aspects and embodiments and a pharmaceutically acceptable carrier, diluent, or excipient.
- the pharmaceutically acceptable carrier, diluent, or excipient is selected from the group consisting of a stabilizer, buffer, surfactant, filler, solvent, tonicity or osmolarity adjusting agent, antioxidant, adjuvant, and antimicrobial agent.
- the blood disorder is selected from the group consisting of von Willebrand disease (VWD), Heydes syndrome, hemophilia A, disorders of platelet function, and connective tissue disorders.
- VWD von Willebrand disease
- the VWD is congenital VWD (cVWD) or acquired VWD (aVWD).
- the VWD is type 1, type 2 A, type 2B, type 2M, type 2N, or type 3.
- a composition disclosed herein treats one or more (e.g., 1, 2, 3, 4, 5, 6 ,7, 8, 9, 10, or more) symptoms of the blood disorder selected from the group consisting of epistaxis, cutaneous bleeding, bleeding from minor wounds, oral-cavity bleeding, angiodysplasia, gastrointestinal bleeding, bleeding from tooth extraction, postoperative bleeding, heavy menstrual bleeding, obstetric hemorrhage, hematuria, muscle hematoma, joint bleeding, visceral bleeding, and central nervous system (CNS) bleeding.
- a composition or pharmaceutical composition disclosed herein promotes platelet adhesion, activation, and aggregation in the subject.
- a VWF protein in blood plasma of a subject in need thereof comprising administering to the subject a composition comprising a monospecific antibody of the foregoing aspects and embodiments.
- methods of accumulating a FVIII protein in blood plasma of a subject in need thereof comprising administering to the subject a composition comprising a monospecific antibody of the foregoing aspects and embodiments.
- a composition comprising a monospecific antibody of the foregoing aspects and embodiments.
- compositions comprising a monospecific antibody disclosed herein and a pharmaceutically acceptable carrier, diluent, or excipient.
- the pharmaceutically acceptable carrier, diluent, or excipient is selected from the group consisting of a stabilizer, buffer, surfactant, filler, solvent, tonicity or osmolarity adjusting agent, antioxidant, adjuvant, and antimicrobial agent.
- a pharmaceutical composition disclosed herein is administered in combination with one or more (e.g., 1, 2, 3, 4, 5, or more) additional therapeutic modalities.
- the one or more additional therapeutic modalities is one or more therapeutic agents.
- the one or more therapeutic agents is selected from the group consisting of desmopressin (DDAVP), tranexamic acid (TXA), thalidomide, tamoxifen, ocreotide, a concentrate of plasma-derived VWF protein, a concentrate of VWF protein in complex with FVIII (VWF :F VIII; e.g., Humate P and Wilate), a concentrate of recombinant VWF protein (e.g., Vonicog alfa), a concentrate of FVIII protein (e.g., Alphanate and Koate-HP), hormonal treatment (e.g., an oral contraceptive pill, e.g., an estrogen-containing contraceptive and an intrauterine device).
- DDAVP desmopressin
- TXA tranexamic acid
- thalidomide e.g., thalidomide
- tamoxifen e.g., thalidomide
- thalidomide e.g.
- the one or more additional therapeutic modalities is surgery. In some embodiments, the one or more additional therapeutic modalities is blood transfusion. In some embodiments, the one or more additional therapeutic modalities is platelet transfusion. In some embodiments, the one or more additional therapeutic modalities is cauterization. In some embodiments, the one or more additional therapeutic modalities is gene therapy. In some embodiments, the gene therapy is FVIII gene therapy. For example, an antibody or composition of the disclosure may be administered in combination with a FVIII gene therapy to extend the half-life of FVIII and/or promote accumulation of FVIII in blood plasma of a subject.
- an antibody or composition of the disclosure is administered to a patient for whom FVIII gene therapy alone is insufficient to attain therapeutically effective levels of FVIII in blood plasma. In some embodiments, an antibody or composition of the disclosure achieves therapeutically effective levels of FVIII in blood plasma.
- the one or more additional therapeutic modalities are administered to the subject prior to, concurrently with, or subsequent to administration of the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject prior to administration of the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject concurrently with the composition or the pharmaceutical composition. In some embodiments, the one or more additional therapeutic modalities are administered to the subject subsequent to administration of the composition or the pharmaceutical composition.
- kits comprising a monospecific antibody or a pharmaceutical composition of the foregoing aspects and embodiments, and a package insert instructing a user of the kit to perform a method of the foregoing aspects and embodiments.
- a monospecific antibody or the pharmaceutical composition of the foregoing embodiments is for use in the treatment of a blood disorder characterized by excessive bleeding.
- the blood disorder characterized by excessive bleeding is selected from the group consisting of VWD, Heydes syndrome, hemophilia A, disorders of platelet function, and connective tissue disorders.
- the VWD is cVWD or aVWD.
- the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
- reference to a range of 1-5,000 fold includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 fold, etc., as well as 1.1, 1.2, 1.3, 1.4, 1.5 fold, etc., 2.1, 2.2, 2.3, 2.4, 2.5 fold, etc., and so forth.
- “About” a number refers to range including the number and ranging from 10% below that number to 10% above that number. “About” a range refers to 10% below the lower limit of the range, spanning to 10% above the upper limit of the range.
- the term “accumulation” refers to an increase in a level (e.g., concentration) of a particular protein, such as, e.g., VWF or FVIII, in a blood compartment (e.g., blood plasma) of a subject following administration of an antibody of the disclosure or a composition (e.g., pharmaceutical composition) containing the same to the subject.
- Various factors may influence the rate of accumulation of a protein in a blood compartment of a subject, including but not limited to, the half-life of the target protein and/or the antibody in the blood compartment, the rate of sequestration of the protein by other tissues, clearance of the protein from the body, among others.
- accumulation of a target protein may result in a blood plasma level of the protein that is at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11- fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, or 20-fold greater as compared to a blood plasma level of the protein in the absence of the antibody.
- accumulation of the target protein may results in a blood plasma level of the protein that is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, 1,000%, 1,500%, 2,000%, 2,500%, 3,000%, 3,500%, 4,000%, 4,500%, 5,000%, 5,500%, 6,000%, 6,500%, 7,000%, 7,500%, 8,000%, 8,500%, 9,000%, 9,500%, 10,000%, or greater as compared to a blood plasma level of the protein in the absence of the antibody.
- accumulation of a protein results directly from specific binding of an antibody of the disclosure to the protein.
- accumulation of a protein results indirectly from binding of the protein (e.g., FVIII) to another protein (e.g., VWF) bound by an antibody of the disclosure.
- antibody refers to a naturally-occurring or non-naturally-occurring protein that binds an antigen.
- An antibody often comprises a variable domain and a constant domain in each of a heavy chain and a light chain. Accordingly, most antibodies have a heavy chain variable domain (VH) and a light chain variable domain (VL) that together form the portion of the antibody that binds to the antigen, sometimes referred to as the “antigen receptor.” Within each variable domain are three complementarity-determining regions (CDR), which form loops in the VH and VL and contact the surface of the antigen.
- VH heavy chain variable domain
- VL light chain variable domain
- CDR complementarity-determining regions
- Antibody includes, but is not limited to monoclonal antibodies, monospecific antibodies, monovalent antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized antibodies, chimeric antibodies, synthetic antibodies, recombinant antibodies, hybrid antibodies, mutated antibodies, grafted antibodies, antibody fragments, and in vitro-generated antibodies having the antigen-binding activity.
- the term also includes antibody conjugates having advantageous properties as compared to an unconjugated antibody (e.g., antibodies conjugated to a half-life extending moiety, e.g., a fatty acid)).
- CDRs complementarity-determining regions
- hypervariable regions refer to the parts of the variable domains in antibodies that determine the antibodies’ binding specificities to their specific antigen.
- a single variable region of an antibody polypeptide will typically comprise three CDRs, usually designated CDR1, CDR2, and CDR3. More particularly, a heavy chain variable region may contain CDRs designated Hl, H2, and H3; likewise, light chain variable region may contain CDRs LI, L2, and L3. Multiple methods may be used to define a CDR. The current art utilizes various numbering schemes with different definitions of CDR lengths and positions.
- IMGT numbering scheme is a standardized numbering system based on alignments of sequences from a complete reference gene database including the whole immunoglobulin superfamily.
- the Kabat numbering scheme is based on sequence alignment and uses "variability parameter" of a given amino acid position (the number of different amino acids at a given position divided by the frequency of the most occurring amino acid at that position) to predict CDRs.
- the Chothia numbering scheme is a structure-based numbering scheme where antibody crystal structures are aligned as define the loop structures as CDRs.
- the Martin numbering scheme focuses on the structure alignment of different framework regions of unconventional lengths.
- Honneger's numbering scheme is based on structural alignments of the 3D structure of the variable regions and uses structurally conserved Ca positions to deduce framework and CDR lengths.
- CDR sequences of a given heavy or light chain variable region may vary depending on the numbering system used. Any method of defining a CDR is contemplated with the sequences disclosed herein. Unless stated otherwise, the CDRs disclosed herein are defined according to the IMGT numbering scheme.
- antibody fragment refers to one or more fragments of an antibody that retain the ability to specifically bind to the antigen.
- Non-limiting examples of antibody fragments included within such terms include, but are not limited to, e.g., a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CHI domains.
- one-arm antibodies comprising a single heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain.
- blood disorder characterized by excessive bleeding refers to one or more disorders in a subject (e.g., a human) that confers a susceptibility to bleed to the subject (e.g., bleeding diathesis). Such a disorder is, in some embodiments, due to a condition associated with atypical and slow blood clotting.
- a “blood disorder characterized by excessive bleeding” may be genetic or acquired in origin. Platelet activation, adhesion, and/or aggregation (e.g., primary hemostasis) is, in some embodiments, impaired in a subject with said disorder.
- function or expression of blood proteins that mediate or facilitate the production of insoluble cross-linked fibrin proteins during blood coagulation is impaired in a subject with the disorder.
- a blood disorder characterized by excessive bleeding include von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders.
- VWD von Willebrand disease
- hemophilia A disorders of platelet function
- connective tissue disorders include von Willebrand disease (VWD), hemophilia A, disorders of platelet function, and connective tissue disorders.
- the VWD is congenital VWD (cVWD) or acquired VWD (aVWD).
- the aVWD includes Heydes syndrome.
- the VWD is type 1, type 2A, type 2B, type 2M, type 2N, or type 3.
- the term “change in function” when referring to the VWF protein means an increase or a decrease by any amount (e.g., increase or decrease by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or increase by 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 600%, 700%, 800%, 900%, 1000%, 2000%, 3000%, 4000%, 5000%, 6000%, 7000%, 8000%, 9000%, 10000%, or more) in the intrinsic function of the VWF protein when bound to an antibody of the disclosure.
- VWF lacks enzymatic activity and its function is associated with binding and stabilization of other proteins involved in blood clotting. Therefore, the function of VWF is primarily to bind to other proteins, including binding partners described herein. Accordingly, a “change in function” of VWF corresponds to an increase or decrease in the ability of VWF to bind to other proteins, such as, e.g., its binding partners.
- the term “complex” refers to a molecular entity formed by two or more physically associated molecules (e.g., proteins), such as, e.g., a VWF protein and an antibody described herein.
- the two or more molecules are associated by any physical means, including covalent bonds, ionic bonds, hydrogen bonds, and van der Waal forces.
- a physical association between the two or more molecules is reversible.
- a physical association between the two or more molecules is irreversible.
- the term “effective amount” as used herein refers to that amount of an antibody, or an antigen-binding portion thereof as described herein, that is sufficient to induce a disclosed effect, e.g., to effect treatment (e.g., accumulation of a VWF and/or FVIII protein in blood plasma), prognosis, or diagnosis of a disease (e.g., a blood disorder characterized by excessive bleeding), as described herein, when administered to a subject.
- Therapeutically effective amounts of antibodies provided herein when used alone or in combination, will vary depending upon the relative activity of the disclosed antibodies and combinations (e.g., in treating, reducing, or ameliorating a disease or disorder described herein) and depending upon the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration, and the like, which, in some cases, are readily determined by one of ordinary skill in the art.
- the term “monospecific” refers to an antibody that displays a preferential affinity for one particular epitope (e.g., an epitope contained in a CK domain of the VWF protein, such as, e.g., a human, NHP, murine, or canine VWF protein).
- the term “monovalent” refers to a property of an antibody or antigen- binding fragment thereof in which the antibody has one antigen-binding site to a target epitope of a particular protein.
- an monovalent antibody of the disclosure binds to an epitope (e.g., an epitope in a CK domain) of a VWF protein with a single antigenbinding site.
- a monovalent antibody is, in some embodiments, a one-armed antibody (e.g., having a heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain).
- one-armed antibody or “single-armed antibody” refer to a type of monovalent antibody fragment containing an antibody heavy chain, a truncated heavy chain lacking a Fab region, and a single light chain.
- Percent identity and “% identity” refers to the extent to which two sequences (nucleotide or amino acid) have the same residue at the same positions in an alignment.
- an amino acid sequence is X% identical to SEQ ID NO: Y refers to % identity of the amino acid sequence to SEQ ID NO: Y and is elaborated as X% of residues in the amino acid sequence are identical to the residues of sequence disclosed in SEQ ID NO: Y.
- computer programs are employed for such calculations. Exemplary programs that compare and align pairs of sequences, include ALIGN (Myers and Miller, Comput Appl Biosci.
- polypeptide refers to a chain of amino acids (e.g., naturally-occurring or non-naturally-occurring amino acids). In some embodiments, the polypeptide comprises amino acids that are naturally-occurring.
- the polypeptide comprises amino acids that are non-naturally-occurring (cystine, desmosine, isodesmosine, hydroxyproline, hydroxylysine, gamma-carboxyglutamate, phosphoserine, phosphothreonine, phosphotyrosine, N-acetyl lysine, methyllysine, inositol, L-homoalanine, L-2-aminobutyric acid, L-azidohomoalanine, beta-phenylalanine, norleucine, 3-fluorotyrosine, 4- fluorophenylalanine, L-3,4-dyhydroxyphenylalanine, pNCSF, L-(7-hydroxycoumarin-4- yl)ethylglycine, 2,3 -dihydroxypropyl cysteine, arylglycine, PrDiAzK, (S)-N-(2- Benzoylphenyl)-l
- polypeptides are not limited to a specific length of the product (e.g., polypeptides can comprise at least 2 amino acids linked together by way of peptide bonds).
- Peptides, oligopeptides, and proteins are included within the definition of polypeptide, and such terms are used interchangeably herein unless specifically indicated otherwise.
- This term also encompasses chains of peptides with post-expression modifications, e.g., glycosylation, acetylation, phosphorylation, and the like, as well as other modifications known in the art, both naturally occurring and non-naturally occurring.
- a polypeptide is an entire protein, or a fragment thereof.
- the terms “preferentially binds” or “specifically binds” mean that the antibodies or fragments thereof bind to an epitope with greater affinity than it binds unrelated amino acid sequences, and, if cross-reactive to other polypeptides containing the epitope, are not toxic at the levels at which they are formulated for administration to human use.
- such affinity is at least 1.5-fold greater, 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, 10-fold greater, at least 20-fold greater, at least 30- fold greater, at least 40-fold greater, at least 50-fold greater, at least 58-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 94-fold greater, or at least 1000-fold greater than the affinity of the antibody or fragment thereof for unrelated amino acid sequences.
- the terms “recipient,” “individual,” “subject,” “host,” and “patient,” are used interchangeably herein and refer to any mammalian subject for whom diagnosis, treatment, or therapy is desired, particularly humans.
- “Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and laboratory, zoo, sports, or pet animals, such as dogs, horses, cats, cows, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, etc.
- the mammal is a human. None of the terms require the supervision of a medical professional.
- the term “specific” refers to a situation in which an antibody will preferentially bind to molecules other than the antigen containing the epitope recognized by the antibody.
- the term is also applicable where e.g., an antigen-binding domain is specific for a particular epitope which is carried by a number of antigens, in which case the antibody or antigenbinding fragment thereof carrying the antigen-binding domain will be able to bind to the various antigens carrying the epitope.
- terapéuticaally effective amount generally refers to an amount of a disclosed antibody or a drug effective to “treat” a disease or disorder in a subject or mammal.
- a composition described herein is administered to a subject in an amount that is effective for producing some desired therapeutic effect by inhibiting a disease or disorder as described herein at a reasonable benefit/risk ratio applicable to any medical treatment.
- a therapeutically effective amount is an amount that achieves at least partially a desired therapeutic or prophylactic effect in an organ or tissue.
- the amount of an antibody necessary to bring about prevention and/or therapeutic treatment of a disease or disorder is not fixed per se.
- the amount of the antibody administered varies with the type of disease, extensiveness of the disease, and size of the mammal suffering from the disease or disorder.
- therapeutically effective means that, after treatment, one or more signs or symptoms of the disease or disorder is ameliorated or eliminated.
- An effective response of the present disclosure is achieved when the subject experiences partial or total alleviation or reduction of signs or symptoms of illness and, in the case of the treatment of a disease (e.g., a blood disorder characterized by excessive bleeding), specifically includes, without limitation, amelioration of symptoms, prolongation of progression, cure, remission, prolongation of survival, or other objective responses.
- a disease e.g., a blood disorder characterized by excessive bleeding
- the expected progression-free survival times are measured in months to years, depending on prognostic factors including the number of relapses, stage of disease, and other factors.
- Prolonging survival includes without limitation times of at least 1 month (mo.), about at least 2 mos., about at least 3 mos., about at least 4 mos., about at least 6 mos., about at least 1 year, about at least 2 years, about at least 3 years, etc. Overall survival is also measured, e.g., in months to years.
- an effective response in some embodiments, is that a subject’s symptoms remain static. Further indications of treatment of indications are described in more detail below.
- administration of a therapeutic agent in a prophylactic method occurs prior to the manifestation of symptoms of an undesired disease or disorder, such that the disease or disorder is prevented or, alternatively, delayed in its progression.
- therapeutically effective means that, after treatment, a smaller number of subjects (on average) develop the undesired disease or disorder or progress in severity of symptoms.
- treatment refers to administering an agent, or carrying out a procedure, for the purposes of obtaining an effect.
- the effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or is therapeutic in terms of effecting a partial or complete cure for a disease and/or symptoms of the disease.
- Treatment includes treatment of a disease or disorder (e.g., blood disorder characterized by excessive bleeding) in a mammal, particularly in a human, and includes: (a) preventing the disease or a symptom of a disease from occurring in a subject which is predisposed to the disease but has not yet been diagnosed as having it (e.g., including diseases that is associated with or caused by a primary disease; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease.
- a disease or disorder e.g., blood disorder characterized by excessive bleeding
- treating includes to any indicia of success in the treatment or amelioration or prevention of a disease or disorder, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the disease condition more tolerable to the patient; slowing in the rate of degeneration or decline; or making the final point of degeneration less debilitating.
- the treatment or amelioration of symptoms is based on one or more objective or subjective parameters, including the results of an examination by a physician.
- treating includes the administration of the agents of the present disclosure to prevent or delay, to alleviate, or to arrest or inhibit development of the symptoms or conditions associated with diseases.
- therapeutic effect refers to the reduction, elimination, or prevention of the disease, symptoms of the disease, or side effects of the disease in the subject.
- a subject is “treated” for a disease or disorder if, after receiving a therapeutic amount of an antibody of the present disclosure, the patient shows observable and/or measurable change in a parameter or symptom of the disease or disorder.
- FIG. 1 shows a flowchart of the protocol used for selection of antibodies that specifically bind to the cysteine knot (CK) domain of human von Willebrand Factor (VWF) protein.
- CK cysteine knot
- VWF von Willebrand Factor
- FIG. 2 shows an overview of the experimental setup used for measurement of the apparent equilibrium dissociation constant (Ka) between monovalent (one-arm; OA) anti- VWF CK domain antibody and CK domain of VWF.
- Ka apparent equilibrium dissociation constant
- FIG. 3 shows a bar graph illustrating the distribution of low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW) VWF multimers following overnight incubation of normal human plasma with 600 nM of monovalent (one-arm) antibody and 1.5 mg/mL ristocetin.
- Two control conditions include plasma without antibody and ristocetin (Untreated) and plasma treated with ristocetin only (Control). Results are shown as mean ⁇ standard deviation across plasma from three healthy human donors.
- FIG. 4A-4E are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) Libl_Pl_A6 (Lib_Pl_A6 OA) antibody administered subcutaneously at 4 mg/kg on day 1 and 2 to two cynomolgus monkeys (“cynos”; 3FG2 and 4FG2, respectively).
- FIG. 4B VWF antigen (VWF:Ag; Example 15),
- FIG. 4C VWF ristocetin cofactor activity (VWF:RCo; Example 18),
- FIG. 4D distribution of low (LMW), intermediate (IMW) and high (HMW) molecular weight VWF multimers (Example 19), and
- FVIII antigen FVIII: Ag; Example 20).
- FIGS. 5A-5E are plots showing pharmacokinetics and pharmacodynamics of monovalent (one-arm) Libl_Pl_A9 (Lib_Pl_A9 OA) antibody administered subcutaneously at 4 mg/kg on day 1 and 2 to two cynos (1MG1 and 2FG1, respectively).
- VWF von Willebrand Factor
- pharmaceutical compositions containing the disclosed antibody and one or more pharmaceutically acceptable carriers, diluents or excipients are also disclosed herein.
- the disclosure also provides methods of using the disclosed antibodies or compositions containing the same for the treatment of a blood disorder characterized by excessive bleeding (e.g., von Willebrand disease (VWD), Hey des syndrome, hemophilia A, disorders of platelet function, and connective tissue disorders).
- a subject with a blood disorder characterized by excessive bleeding is treated in accord with the methods disclosed herein by administering an antibody of the disclosure or a composition containing the same (e.g., a pharmaceutical composition) to the subject by any acceptable route (e.g., subcutaneously).
- an antibody of the disclosure or a composition containing the same e.g., a pharmaceutical composition
- Blood circulation provides cells and tissues with necessary substances such as nutrients and oxygen and disposes of metabolic waste products from these cells.
- the blood vasculature establishes a physical barrier that ensures the containment of blood, regulation of its pressure throughout the organism, and tissue-directed delivery of nutrients and waste products. Disruption or damage to this barrier can result in potentially life-threatening blood loss.
- Blood plasma contains numerous soluble proteins that act in a concerted cascade of enzymatic reactions to produce a blood clot that can readily “plug” the damaged blood vessel and prevent or reduce further blood loss. This plug is stabilized by the proteolytic cleavage of fibrinogen into fibrin, which forms a mesh that ensheathes and reinforces the clot.
- hemostasis Formation and degradation of blood clots are part of a process called hemostasis, which is regulated by a number of soluble and membrane-tethered pro-coagulant and anti -coagulant proteins.
- a balance between coagulation and fibrinolysis i.e., degradation of insoluble fibrin proteins controls the stability of the blood clot.
- zymogens i.e., inactive protein precursors
- proteolytic cleavage a serine protease that activates downstream zymogens to drive clot formation.
- Protein cofactors also act in the blood clotting cascade, generally circulating as inactive pro-cofactors in blood plasma until activated by limited proteolysis.
- the extrinsic pathway is initiated when a cell-surface complex of an integral membrane protein, tissue factor (TF), and Factor Vila (TF:VIIa) activates Factor IX (FIX) and Factor X (FX) by limited proteolysis, thereby producing activated FIX (FIXa) and activated FX (FXa).
- the contact pathway initiates when Factor Xlla (FXII), prekallikrein (PK), and kininogen (HK) assemble on a surface or polymer. Assembly results in reciprocal activation of FXII to FXIIa by kallikrein (KK), and PK to KK by FXIIa.
- FXIIa then activates Factor XI (FXI) to FXIa, which then enzymatically converts FIX to FIXa.
- Activated FVIII (FVIIIa) combines with FIXa to form an Xase (FVIIIa:FIXa) complex responsible for the generation of FXa together with the initiating TF:FVIIa complex.
- Extrinsic and intrinsic pathways ultimately converge on the production of FXa, which leads to the activation of thrombin from prothrombin, thrombin-mediated cleavage of fibrinogen to fibrin, and activation, adhesion, and aggregation of platelets at the site of the clot.
- VWF plays a critical role in platelet adhesion, activation, and aggregation during blood coagulation.
- Increased local shear stress near sites of vascular injury results in VWF binding to collagen in the sub-endothelial membrane, which in turn induces platelets to attach to tethered VWF by way of surface glycoprotein to initiate formation of the platelet plug.
- the interaction between VWF and platelets occurs strictly in the context of vascular damage, since VWF does not interact with circulating platelets in the absence of injury.
- the Al and C4 domains of VWF are essential for binding with platelet glycoproteins, such as, e.g., the platelet gplb and gpllbllla receptors, respectively.
- VWF and FVIII circulate as a complex in plasma under physiological conditions, accumulation of VWF at the site of vascular injury may increase the local concentration of FVIII. Similarly, reduced levels of VWF, as occurs, e.g., in VWD, may lead to reduced levels of FVIII.
- the thrombomodulin-thrombin complex can enzymatically activate the thrombin-activatable fibrinolysis inhibitor (TAFI) protein, a carboxypeptidase enzyme that reduces fibrinolysis by removing C-terminal lysine residues exposed on fibrin that are critical for the conversion of plasminogen to plasmin.
- TAFFs ability to attenuate fibrinolysis is highly dependent on its concentration, rate of activation, and blood plasma half-life.
- AT antithrombin
- serpin serine protease inhibitor
- the mature VWF polypeptide is a large (2,050 amino acid residues) blood glycoprotein that functions in hemostasis and platelet adhesion.
- VWF is generally localized to the blood plasma, vascular endothelium, megakaryocytes, and subendothelial connective tissue, and exists in multimers of various sizes ranging from about 500 to 20,000 kDa.
- VWF multimer size typically scales with its role in hemostasis, i.e., larger VWF multimers are more effective at promoting clotting. Different domains of VWF are involved different functions.
- VWF contains the following domains, from N-terminus to C-terminus: D1-D2-D’- D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK.
- the D1-D2 domains corresponding to the VWF propeptide, are proteolytically cleaved during processing of VWF into mature VWF.
- the D’-D3 domain mediates multimerization of VWF dimers and also binds to Factor VIII.
- the Al domain binds to platelet gplb receptor, heparin, and collagen.
- the A2 domain is cleaved by ADAMTS13, resulting in generation of smaller VWF multimers.
- the A3 domain binds to collagen.
- the C4 domain binds to platelet to gpIIa/IIIb.
- the CK domain is important for tail-to-tail homodimerization of VWF monomers (Springer, J Thromb Hemo 9: 130-43 (2011)). Binding of VWF to other proteins, such as, e.g., FVIII, results in the stabilization of the binding partner and increases its blood plasma half-life. For example, in the absence of VWF, FVIII has a half-life of about 1-2 hours, but extends to 8-12 hours when bound by VWF. In addition to acting as a carrier of FVIII, VWF promotes clotting by facilitating platelet adhesion, activation, and aggregation. Deficiency or dysfunction of VWF is associated with a tendency to bleed and occurs in a number of blood disorders characterized by excessive bleeding, including, e.g., VWD and Hey des syndrome.
- the VWF protein is a human VWF protein.
- the human VWF protein has an amino acid sequence having at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 1.
- the human VWF protein has an amino acid sequence having at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 1. In some embodiments, the human VWF protein has an amino acid sequence of SEQ ID NO: 1.
- the VWF protein is a VWF protein of a non-human primate (NHP; e.g., Macaca fascicularis).
- NHP VWF protein has an amino acid sequence having at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 2.
- the NHP VWF protein has an amino acid sequence having at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence having at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the NHP VWF protein has an amino acid sequence of SEQ ID NO: 2.
- the VWF protein is a VWF protein of a canine (e.g., Canis familiaris).
- the canine VWF protein has an amino acid sequence having at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence having at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 3.
- the canine VWF protein has an amino acid sequence having at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, the canine VWF protein has an amino acid sequence of SEQ ID NO: 3.
- the VWF protein is a VWF protein of a mouse (e.g., Mus musculus).
- the murine VWF protein has an amino acid sequence having at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 4.
- the murine VWF protein has an amino acid sequence having at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence having at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, the murine VWF protein has an amino acid sequence of SEQ ID NO: 4.
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 12.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 12 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 16.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 16 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 17, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of KAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 18.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 12 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 13, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 14, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 15; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 453.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 473.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 463.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 453, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 473, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 19 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 23.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 23 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 24, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of AAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 25.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 19 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 20, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 21, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 22; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 454.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 474.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 464.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 454, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 474, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 26 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 30.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 30 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 31, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of ESS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 32.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 26 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 27, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 28, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 29; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 33 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 37.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 37 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 38, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 39.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 33 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 34, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 35, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 36; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 455.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 475.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 465.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 455, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 475, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 40.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 40 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 44.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 44 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 45, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GSS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 46.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 40 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 41, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 42, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 43; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 456.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 476.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 466.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 456, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 476, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 47 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 51.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 51 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 52, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 53.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 47 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 48, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 49, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 50; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 54 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 58.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 58 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence SEQ ID NO: 59, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 60.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 54 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 55, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 56, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 57; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 457.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 477.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 467.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 457, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 477, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 61 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 65.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 65 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 66, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 67.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 61 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 62, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 63, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 64; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 68 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 72.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 72 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 73, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 74.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 68 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 69, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 70, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 71; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 75 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 79.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 79 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 80, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of HAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 81.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 75 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 76, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 77, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 78; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 82 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 86.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 86 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 87, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 88.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 82 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 83, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 84, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 85; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 89 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 93.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 93 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 94, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 95.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 89 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 90, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 91, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 92; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 458.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 478.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 468.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 458, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 478, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 96 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 100.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 100 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 101, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 102.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 96 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 97, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 98, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 99; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 103.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 107.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 103 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 107.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 107 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 108, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DIS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 109.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 103 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 104, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 105, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 106; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 110.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 114.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 110 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 114.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 114 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 115, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 116.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 110 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 111, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 112, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 113; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 8
- VH
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 459.
- HC first heavy chain
- the antibody comprises a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 479.
- the antibody comprises a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 469.
- LC light chain
- the antibody comprises a first heavy chain (HC) region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 459, a second heavy chain region comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 479, and a light chain (LC) region, comprising an amino acid sequence having at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 8
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 117.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 121.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 117 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 121.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 121 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 122, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 123.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 117 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 118, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 119, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 120; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 124.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 128.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 124 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 128.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 128 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 129, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of EAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 130.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 124 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 125, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 126, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 127; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 131.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 135.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 131 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 135.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 135 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 136, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 137.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 131 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 132, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 133, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 134; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 138.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 142.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 138 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 142.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 142 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 143, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 144.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 138 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 139, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 140, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 141; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 145.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 149.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 145 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 149.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 149 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 150, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 151.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 145 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 146, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 147, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 148; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 152.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 156.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 152 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 156.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 156 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 157, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 158.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 152 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 153, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 154, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 155; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 159.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 163.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 159 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 163.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 163 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 164, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 165.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 159 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 160, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 161, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 162; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 8
- VH
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 166.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 170.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 166 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 170.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 170 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 171, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 172.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 166 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 167, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 168, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 169; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 173.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 177.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 173 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 177.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 177 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 178, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 179.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 173 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 174, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 175, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 176; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 180.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 184.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 180 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 184.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 184 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 185, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DVS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 186.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 180 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 181, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 182, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 183; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 187.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 191.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 187 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 191.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 191 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 192, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 193.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 187 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 188, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 189, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 190; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 194.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 198.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 194 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 198.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 198 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 199, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 200.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 194 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 195, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 196, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 197; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 201.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 205.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 201 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 205.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 205 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 206, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GVD, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 207.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 201 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 202, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 203, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 204; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 208.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 212.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 208 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 212.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 212 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 213, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 214.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 208 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 209, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 210, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 211; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 215.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 219.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 215 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 219.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 219 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 220, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAT, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 221.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 215 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 216, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 217, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 218; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 222.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 226.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 222 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 226.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 226 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 227, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 228.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 222 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 223, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 224, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 225; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 229.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 233.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 229 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 233.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 233 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 234, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of DAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 235.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 229 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 230, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 231, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 232; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 236.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 240.
- the antibody comprises: (a) a complementarity determining SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 236 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 240.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 240 and comprising therein a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 241, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 242.
- VL variable light chain
- the antibody comprises: (a) a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 236 and comprising therein a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 237, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 238, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 239; and (b) a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%,
- VL
- the antibody comprises a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246.
- the antibody comprises a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243.
- VH variable heavy chain
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 243.
- the antibody comprises a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 247.
- the antibody comprises: (a) a complementarity determining region (CDR) Hl having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 244, a CDR H2 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 245, and a CDR H3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 246; and (b) a complementarity determining region (CDR) LI having 100% sequence identity to an amino acid sequence of SEQ ID NO: 248, a CDR L2 having an amino acid sequence 100% identical to the amino acid sequence of GAS, and a CDR L3 having an amino acid sequence 100% identical to the amino acid sequence of SEQ ID NO: 249.
- CDR complementarity determining region
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 80% (e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 85% (e.g., at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 90% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- VH variable heavy chain
- VL variable light chain
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence with at least 95% (e.g., at least 95%, 96%, 97%, 98%, 99%, or more) identity to SEQ ID NO: 247.
- the antibody comprises a variable heavy chain (VH) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 243 and a variable light chain (VL) region having an amino acid sequence 100% identical with the amino acid sequence of SEQ ID NO: 247.
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| AU2023221511A AU2023221511A1 (en) | 2022-02-15 | 2023-02-14 | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
| KR1020247030582A KR20240159860A (ko) | 2022-02-15 | 2023-02-14 | Vwf 표적화 단일특이적 항체를 사용한 혈액 장애의 치료 방법 |
| CN202380034172.8A CN119032109A (zh) | 2022-02-15 | 2023-02-14 | 用靶向vwf的单特异性抗体治疗血液病症的方法 |
| JP2024569671A JP2025507448A (ja) | 2022-02-15 | 2023-02-14 | Vwf標的化単特異性抗体により血液障害を処置する方法 |
| US18/838,515 US20250154283A1 (en) | 2022-02-15 | 2023-02-14 | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
| CA3244108A CA3244108A1 (en) | 2022-02-15 | 2023-02-14 | METHODS FOR TREATING BLOOD DISORDERS WITH MONOSPACTIC ANTIBODY TARGETING VWF |
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| WO2025037032A1 (en) * | 2023-08-16 | 2025-02-20 | Hemab Aps | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
| WO2025174998A1 (en) * | 2024-02-13 | 2025-08-21 | Invetx, Inc. | Anti-il-31ra antibodies and uses thereof |
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| WO2018203086A1 (en) * | 2017-05-04 | 2018-11-08 | Imperial Innovations Limited | Truncated vwf |
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| WO2025037032A1 (en) * | 2023-08-16 | 2025-02-20 | Hemab Aps | Methods of treating blood disorders with vwf-targeted monospecific antibodies |
| WO2025174998A1 (en) * | 2024-02-13 | 2025-08-21 | Invetx, Inc. | Anti-il-31ra antibodies and uses thereof |
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| KR20240159860A (ko) | 2024-11-06 |
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