Antibodies that bind C1S and uses thereof

Abstract

Embodiments provided herein relate to antibodies and compositions that bind to C1s. Also provided are methods of producing the antibodies of the disclosure, as well as the use of the provided antibodies and compositions for the treatment of C1s mediated diseases and disorders.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 590,980, filed Oct. 17, 2023; U.S. Provisional Application No. 63 / 501,807, filed May 12, 2023; U.S. Provisional Application No. 63 / 485,765, filed Feb. 17, 2023; and U.S. Provisional Application No. 63 / 384,537, filed Nov. 21, 2022, each of which is incorporated herein by reference in its entirety.

[0003] Reference to Electronic Sequence Listing

[0004] This application contains a Sequence Listing, which is submitted electronically in XML format and is incorporated herein by reference in its entirety. The Sequence Listing is named “DIN002WOsequencelisting.xml,” was created on Nov. 17, 2023, and is 495,158 bytes in size. Field of the Invention

[0005] The field of the invention is immunology, particularly therapeutic antibodies, and the treatment of diseases using those antibodies. Background of the Invention

[0006] The complement system is a well-known effector mechanism of the innate immune response that provides protection not only against pathogens and other harmful agents but also plays a role in recovery from injury. Complement activation by autoantibodies and heterologous antibodies can lead to normal cell damage or transplant tissue rejection. The complement pathway consists of many proteins that are normally present in the body in an inactive form. Complement consists of the alternative pathway, the classical pathway, and the lectin pathway and is essential for immune defense. The classical complement pathway is triggered by activation of the first component of complement, which is called the C1 complex and is composed of C1q, C1r, and C1s proteins. When C1 binds to an immune complex or other activating factor, the C1s component and diisopropylfluorophosphate (DFP)-sensitive serine protease cleave complement components C4 and C2 to initiate activation of the classical complement pathway. Binding of C1 to an antigen-antibody complex induces cleavage of the zymogen C1s to the active C1s enzyme and ultimately leads to the formation of the pore-forming membrane attack complex (MAC) responsible for disrupting the neuromuscular junction. The classical complement pathway appears to play a role in many diseases and disorders.

[0007] For example, sutimlimab (TNT009), sold as is an antibody that inhibits C1s to treat hemolysis in adults with cold agglutinin disease.

[0008] However, sutimlimab binds to both the active form of C1s and the inactive zymogen proC1s, and because sutimlimab lacks specificity for either form of C1s, extremely high doses must be administered to overcome the circulating levels of proC1s, which may limit the clinical use of sutimlimab.

[0009] Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by autoantibodies targeting proteins at the neuromuscular junction, which results in impaired neurotransmission, muscle fatigue, and weakness. The most common autoantibodies in myasthenia gravis are anti - nicotinic acetylcholine receptor (AChR), which are proposed to induce pathology through three different mechanisms, including activation of the complement system. The treatment of MG lacks effectiveness.

[0010] Accordingly, there is a need in the art for compounds that treat complement classical pathway - mediated diseases or disorders and are specific for the active form of complement proteins. The embodiments provided herein meet these and other needs. Summary of the Invention

[0011] In some embodiments, there is provided an antibody or an antigen - binding fragment thereof that binds to the active form of C1s. In some embodiments, there is provided an antibody or an antigen - binding fragment thereof that specifically binds to the active form of C1s. In some embodiments, the antibody or an antigen - binding fragment thereof is as provided herein.

[0012] In some embodiments, there is provided a variant of an antibody or an antigen - binding fragment thereof, wherein the variant has 1 to 10 substitutions, deletions, or insertions.

[0013] In some embodiments, there is provided a variant of an antibody or an antigen - binding fragment thereof, wherein the variant has 1 to 10 conservative substitutions.

[0014] In some embodiments, there is provided a recombinant antibody or an antigen - binding fragment thereof, wherein the recombinant antibody or an antigen - binding fragment thereof binds to C1s. In some embodiments, the recombinant antibody or an antigen - binding fragment thereof is the antibody or an antigen - binding fragment thereof as provided herein.

[0015] In some embodiments, there is provided an isolated nucleic acid molecule. In some embodiments, the isolated nucleic acid molecule encodes an antibody or an antigen - binding fragment thereof, a heavy - chain variable region, a light - chain variable region, a heavy chain, a light chain, or a combination thereof. In some embodiments, the antibody or an antigen - binding fragment thereof, the heavy - chain variable region, the light - chain variable region, the heavy chain, or the light chain is as provided herein.

[0016] In some embodiments, there is provided an expression vector. In some embodiments, the expression vector contains the nucleic acid molecule as provided herein.

[0017] In some embodiments, a host cell is provided. In some embodiments, the host cell comprises a nucleic acid molecule or an expression vector as provided herein. In some embodiments, the host cell comprises a nucleic acid molecule as provided herein. In some embodiments, the host cell comprises an expression vector as provided herein.

[0018] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the antibody or the antigen-binding fragment thereof is produced by the host cell.

[0019] In some embodiments, a pharmaceutical composition is provided. In some embodiments, the pharmaceutical composition comprises an antibody or an antigen-binding fragment thereof as provided herein.

[0020] In some embodiments, a method for producing a polypeptide comprising a heavy chain variable region or a light chain variable region is provided. In some embodiments, the method comprises (a) growing a host cell as provided herein under conditions such that the host cell expresses a polypeptide comprising the heavy chain variable region or the light chain variable region; and (b) purifying the polypeptide comprising the heavy chain variable region and / or the light chain variable region. In some embodiments, the heavy chain variable region is as provided herein. In some embodiments, the light chain variable region is as provided herein.

[0021] In some embodiments, a method for producing an antibody or an antigen-binding fragment of the antibody is provided. In some embodiments, the antibody or the antigen-binding fragment binds to human C1s. In some embodiments, the method comprises (a) growing a host cell as provided herein under conditions such that the host cell expresses one or more polypeptides comprising the immunoglobulin heavy chain variable region and / or the immunoglobulin light chain variable region, thereby producing the antibody or the antigen-binding fragment of the antibody; and (b) purifying the antibody or the antigen-binding fragment of the antibody.

[0022] In some embodiments, a method for treating a subject having a C1s-mediated disorder is provided. In some embodiments, the method comprises administering to the subject an antibody or an antigen-binding fragment thereof as provided herein, or a pharmaceutical composition as provided herein.

[0023] In some embodiments, an antibody or an antigen-binding fragment thereof or a pharmaceutical composition is provided, wherein the antibody or an antigen-binding fragment thereof or the pharmaceutical composition is for treating C1s-mediated disorders. In some embodiments, the antibody or an antigen-binding fragment thereof is as provided herein. In some embodiments, the pharmaceutical composition is as provided herein. In some embodiments, the C1s-mediated disorders are as provided herein. In some embodiments, the C1s-mediated disorders are hemolysis, cold agglutinin disease, immune thrombocytopenia (ITP), myasthenia gravis, glomerular lesions, atypical hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), dermatomyositis or anti-MAG neuropathy. In some embodiments, the condition can be caused by a stroke or a spinal cord injury.

[0024] In some embodiments, an antibody or an antigen-binding fragment thereof or a pharmaceutical composition is provided, wherein the antibody or an antigen-binding fragment thereof or the pharmaceutical composition is used as an agent. In some embodiments, the antibody or an antigen-binding fragment thereof is as provided herein. In some embodiments, the pharmaceutical composition is as provided herein.

[0025] In some embodiments, a use of an antibody or an antigen-binding fragment thereof or a pharmaceutical composition is provided, wherein the use is for treating C1s-mediated disorders. In some embodiments, the antibody or an antigen-binding fragment thereof is as provided herein. In some embodiments, the pharmaceutical composition is as provided herein. In some embodiments, the C1s-mediated disorders are as provided herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The amino acid sequence of hProC1s RQ is depicted, where the underlined portion represents the expressed protein secretion signal sequence (first 19 amino acids), the bold portion represents the sequence in which arginine 437 has been changed to glutamate, and the italicized region represents the spacer for protein purification and 10 histidine residues (last 19 amino acids).

[0027] Figures 2A - 2C Shows the binding of hProC1s RQ and human C1s to the antibodies disclosed herein. Figure 2A Shows the binding to antibody 4011g and derivatives. Figure 2B Shows the binding to antibody 5L3g and derivatives. Figure 2C Shows the binding to antibody 191g and derivatives.

[0028] Figure 3Depict the inhibition of antibodies IgG4-MAB17, IgG4-MAB4, and IgG4-MAB9 as disclosed herein in 1% human serum for the Wieslab complement classical pathway assay.

[0029] Figures 4A - 4C Depict the antibodies IgG4-MAB17, IgG4-MAB4, and IgG4-MAB9 as disclosed herein ( Figure 4A ), antibodies 191g, MAB4, and MAB9 ( Figure 4B ), and antibodies MAB2 (US20220380483A1) and MAB9 ( Figure 4C ) for antibody-mediated inhibition of complement-mediated hRBC lysis in 25% human serum.

[0030] Figure 5 Depict the antibody-mediated inhibition of antibodies IgG4-MAB17, IgG4-MAB4, and IgG4-MAB9 as disclosed herein for C3b deposition on hRBCs.

[0031] Figure 6 Show the mean antibody concentrations over time of antibodies IgG4-MAB17, IgG4-MAB4, and IgG4-MAB9 as disclosed herein in cynomolgus monkeys after a single IV injection of 3 or 30 mg / kg body weight (mpk).

[0032] Figure 7 Show the concentration of IgG4-MAB39 in serum diluted to the dilution factor required to obtain 50% sensitized sheep RBC lysis (CH50). The serum was obtained from cynomolgus monkeys treated with a single subcutaneous dose of 20 mg / kg body weight (mpk) of IgG4-MAB39. The concentration of IgG4-MAB39 at CH50 was monitored over time for up to 30 days.

[0033] Figure 8Describe a preclinical cellular model of myasthenia gravis used to evaluate the effect of IgG4-MAB39 on the inhibition of the classical complement pathway in terms of neuromuscular junction functionality. Human induced pluripotent stem cell (iPSC)-derived motor neurons and skeletal muscle cells were co-cultured in a dual-chamber compartmentalized microfluidic device, where motor neurons were cultured on one chamber and muscle cells were cultured on a second chamber. In the absence or presence of IgG4-MAB39 or anti-C5 antibody recombinant ravulizumab (from a published patent), serum (10% concentration) from AChR+MG patients (n = 3) supplemented with pooled normal human serum (1%) retaining complement was added to the skeletal muscle cell reservoir. The motor neuron chamber received electrical stimulation at 2 Hz for 2 minutes, and skeletal muscle contractions were monitored in real time. The muscle contraction fatigue index score was calculated as the area under the curve (AUC) of the region of interest (ROI) divided by the tetanic response of the myotubes (maximum ROI trace height x stimulation duration). IgG4-MAB39 decreased the muscle contraction fatigue index score in the serum of AChR+MG patients, indicating improved neurotransmission, neuromuscular junction functionality, and muscle contraction. The response curve of IgG-MAB39 was similar to that of anti-C5 antibody recombinant ravulizumab. IgG4-MAB39 improved neurotransmission impairment in a physiologically relevant in vitro model of AChR+MG. This finding provides a scientific basis for targeting the classical complement pathway in AChR+MG.

[0034] Figure 9 Show the dose-dependent complete inhibition of the classical pathway by MAB39 and its preclinical precursor MAB9 in the Wieslab assay.

[0035] Figure 10 Show the dose-dependent complete inhibition of the classical pathway by MAB39 and its preclinical precursor MAB9 in the antibody-sensitized sheep red blood cell lysis assay.

[0036] Figure 11 Show the percentage of bacterial survival (%) of Neisseria meningitidis in complement-containing serum with anti-C7 antibody, ravulizumab, or MAB39 and heat-inactivated anticapsular antibody. Detailed Description

[0037] Provided herein are binding proteins, such as antibodies or fragments thereof, that selectively bind to C1s and have low binding affinity for the zymogen proC1s. In some embodiments, the antibody inhibits the activation of the classical complement pathway and can be used in methods for treating complement-mediated disorders, such as but not limited to those provided herein. In some embodiments, the selectivity of C1s relative to proC1s can be used to reduce or prevent target-mediated clearance of therapeutic antibodies, thus requiring lower doses and reduced frequencies of antibody administration.

[0038] Before describing the compositions and methods of the present invention, it should be understood that the scope of the present invention is not limited to the specific processes, compositions, or methods described herein, as these may vary. It should also be understood that the terminology used in this specification is for the purpose of describing particular versions or embodiments only and is not intended to limit the scope of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the embodiments of the methods and systems disclosed herein, the preferred methods, devices, and materials will now be described.

[0039] The following explanations of terms and methods are provided to better describe the present invention and to guide one of ordinary skill in the art in practicing the present invention.

[0040] One of ordinary skill in the art will understand that, given the amino acid sequences of the variable regions of the binding molecules (e.g., antibodies) described herein, the CDR sequences therein can be determined using these or any other protocols for defining CDRs (such as IMGT, Kabat, Chothia, or Contact) with available web tools for determining CDRs in such variable domains based on any known convention. Such tools include the websites

[0041] www.abysis.org / abysis / sequence_input / key_annotation / key_annotation.cgi and

[0042] the tools visible at www.novoprolabs.com / tools / cdr.

[0043] Accordingly, a set of three CDRs in the heavy or light chain variable region based on a CDR protocol disclosed herein is considered equivalent to the equivalent of the same set of CDRs determined according to any other protocol, which may be referred to as "protocol equivalents" or "protocol-equivalent CDRs".

[0044] As used herein, unless the context clearly dictates otherwise, "comprising" means "including", and the singular forms "a", "an", or "the" include plural referents. For example, reference to "comprising a therapeutic agent" includes one or more such therapeutic agents. Unless the context clearly indicates otherwise, the term "or" refers to a single one of the recited alternative elements. For example, the phrase "A or B" refers to A alone, or B alone. The phrase "A, B, or a combination thereof" refers to A alone, B alone, or a combination of A and B. Similarly, "one or more of A and B" refers to a combination of A, B, or both A and B. The phrase "A and B" refers to a combination of A and B. In addition, the various elements, features, and steps discussed herein, as well as other known equivalents for each such element, feature, or step, may be mixed and matched by one of ordinary skill in the art to perform a method in accordance with the principles described herein. Among the various elements, features, and steps, some will be specifically included in a particular example, while others will be specifically excluded.

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although any methods and materials similar or equivalent to those described herein can be used to practice or test the present invention, the suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting. All references cited herein are incorporated herein by reference in their entirety.

[0046] As used herein, the term "antibody" refers to any form of antibody that exhibits the desired biological activity. Thus, it is used in the broadest sense and specifically encompasses (but is not limited to) monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized fully human antibodies, chimeric antibodies, and camelized single-domain antibodies. A "parent antibody" is an antibody obtained by exposing the immune system to an antigen prior to modifying the antibody for a predetermined use, such as humanizing the antibody for use as a human therapeutic antibody.

[0047] As used herein, unless otherwise indicated, "antibody fragment" or "antigen-binding fragment" refers to an antigen-binding fragment of an antibody, i.e., an antibody fragment that retains the ability to specifically bind an antigen bound by the full-length antibody, such as a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include (but are not limited to) Fab, Fab', F(ab')2, and Fv fragments; bispecific antibodies; linear antibodies; single-chain antibody molecules, such as sc-Fv; nanobodies; and multispecific antibodies formed from antibody fragments.

[0048] "Fab fragment" comprises a light chain, and the C of one heavy chain H1 and variable regions. The heavy chain of the Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0049] The "Fc" region contains two heavy chain fragments comprising antibody C H 2 and C H 3 domains. The two heavy chain fragments are held together by two or more disulfide bonds and hydrophobic interactions of the C H 3 domains.

[0050] The "Fab' fragment" contains one light chain and a portion or fragment of a heavy chain containing the V H domain and C H 1 domain, as well as the region between C H 1 and C H 2 domains, such that an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form an F(ab')2 molecule.

[0051] The "F(ab')2 fragment" contains two light chains and two heavy chains containing a portion of the constant region between C H 1 and C H 2 domains, such that an interchain disulfide bond is formed between the two heavy chains. Thus, the F(ab')2 fragment consists of two Fab' fragments held together by a disulfide bond between the two heavy chains.

[0052] The "Fv region" contains the variable regions from the heavy and light chains, but lacks the constant regions.

[0053] The term "single-chain Fv" or "scFv" antibody refers to an antibody fragment containing the V H and V L domains of an antibody, where these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further contains a polypeptide linker between the V H and V L domains that enables the scFv to form the required structure for antigen binding. For a review of scFv, see Pluckthun (1994) The Pharmacology of Monoclonal Antibodies, Volume 113, edited by Rosenberg and Moore, Springer-Verlag, New York, pages 269 - 315. See also International Patent Application Publication No. WO 88 / 01649 and U.S. Patents Nos. 4,946,778 and 5,260,203.

[0054] A "single-domain antibody" is an immunofunctional immunoglobulin fragment containing only the variable region of the heavy chain or the variable region of the light chain. In some cases, two or more VH The regions are covalently linked to a peptide linker to produce a bivalent domain antibody. The two V H regions of the bivalent domain antibody can target the same or different antigens.

[0055] A "bivalent antibody" contains two antigen-binding sites. In some cases, the two binding sites have the same antigen specificity. However, a bivalent antibody can be bispecific (see below).

[0056] In certain embodiments, monoclonal antibodies also include camelid single-domain antibodies herein. See, e.g., Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO 94 / 04678; WO 94 / 25591; U.S. Patent No. 6,005,079). In one embodiment, the invention provides a single-domain antibody that includes two modified VH domains so as to form a single-domain antibody.

[0057] As used herein, the term "bispecific antibody" refers to a small antibody fragment having two antigen-binding sites, the fragment including a heavy-chain variable domain (V H -V L or V L -V H ) linked to a light-chain variable domain (V L ) in the same polypeptide chain (V H ). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domain on the other chain and create two antigen-binding sites. Bispecific antibodies are more fully described, e.g., in EP404,097; WO 93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448. For an assessment of engineered antibody variants, generally see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0058] Typically, the variant antibodies or antigen-binding fragments of the antibodies provided by the present invention retain at least 10% of their C1s-binding activity when expressed in terms of molar concentration of their human C1s-binding activity (when compared to the modified parental antibody). In some embodiments, the variant antibodies (or antigenic fragments thereof) or antigen-binding fragments of the antibodies provided herein retain at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the C1s-binding affinity as the parental antibody. As described herein, the antibodies or antigen-binding fragments of the present invention are also intended to optionally include conservative or non-conservative amino acid substitutions that do not substantially alter their biological activity (referred to as "conservative variants" or "functionally conservative variants" of the antibody).

[0059] "Isolated antibody" refers to a purified state and in this context means that the molecule is substantially free of other biomolecules, such as nucleic acids, proteins, lipids, carbohydrates or other substances (such as cell debris and growth medium). In general, the term "isolated" is not intended to mean the complete absence of such substances or the absence of water, buffer or salt, unless present in an amount that substantially interferes with the experimental or therapeutic use of the binding compound as described herein.

[0060] As used herein, the term "monoclonal antibody" refers to a substantially homogeneous population of antibodies, i.e., the amino acid sequences of the antibody molecules comprising the population are identical except for possible naturally-occurring mutations and / or post-translational modifications present in minor amounts. In contrast, conventional (polyclonal) antibody preparations typically include large numbers of different antibodies that have different amino acid sequences in the variable domains, particularly in the CDRs, and that usually have specificities for different epitopes. The modifier "monoclonal" indicates the character of the antibody as obtained from a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies used according to the present invention can be made by the hybridoma method first described by Kohler et al., (1975) Nature 256:495, or can be prepared by recombinant DNA methods (see, e.g., U.S. Patent No. 4,816,567). "Monoclonal antibodies" can also be isolated from phage antibody libraries using, for example, the techniques described in Clackson et al. (1991) Nature 352:624-628 and Marks et al. (1991) J. Mol. Biol. 222:581-597. See also Presta (2005) J. Allergy Clin. Immunol. 116:731.

[0061] As used herein, a "chimeric antibody" is an antibody having a variable domain from a first antibody and a constant domain from a second antibody, wherein the first and second antibodies are from different species. (U.S. Patent No. 4,816,567; and Morrison et al., (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855). Generally, the variable domain is obtained from an antibody of an experimental animal such as a rodent ("parent antibody"), and the constant domain sequence is obtained from a human antibody, such that the resulting chimeric antibody is less likely to elicit an adverse immune response in a human subject as compared to the parent (e.g., rodent) antibody.

[0062] As used herein, the term "humanized antibody" refers to an antibody form that contains sequences from human and non-human (e.g., murine or rat) antibodies. Generally, a humanized antibody will contain substantially all of at least one and usually two variable domains, wherein all or substantially all of the hypervariable loops correspond to those regions of the non-human immunoglobulin, and all or substantially all of the framework (FR) regions are those regions of the human immunoglobulin sequences. A humanized antibody may optionally contain at least a portion of the human immunoglobulin constant region (Fc).

[0063] The term "fully human antibody" refers to an antibody that contains only human immunoglobulin sequences. If produced in a mouse, in mouse cells, or in a hybridoma derived from mouse cells, a fully human antibody may contain murine carbohydrate chains. Similarly, a "mouse antibody" refers to an antibody that contains only murine immunoglobulin sequences. Alternatively, if produced in a rat, in rat cells, or in a hybridoma derived from rat cells, a fully human antibody may contain rat carbohydrate chains. Similarly, a "rat antibody" refers to an antibody that contains only rat immunoglobulin sequences.

[0064] In some embodiments, the basic antibody structural unit comprises a tetramer. Each tetramer includes two pairs of identical polypeptide chains, each pair having one "light" chain (about 25 kDa) and one "heavy" chain (about 50-70 kDa). The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids that is primarily responsible for antigen recognition. The carboxyl-terminal portion of the heavy chain may define the constant region that is primarily responsible for effector functions. Generally, human light chains are classified as kappa and lambda light chains. In addition, human heavy chains are generally classified as mu, delta, gamma, alpha, or epsilon, and define the isotypes of the antibody as IgM, IgD, IgG, IgA, and IgE, respectively. Within the light and heavy chains, the variable and constant regions are joined by a "J" region of about 12 or more amino acids, wherein the heavy chain also includes a "D" region of about more than 10 amino acids. See generally Fundamental Immunology, Chapter 7 (Paul, W. ed., 2nd ed., Raven Press, N.Y. (1989).

[0065] The variable regions of each light chain / heavy chain pair form the antibody binding site. Thus, generally, an intact antibody has two binding sites. However, except in bispecific or bifunctional antibodies, the two binding sites are usually identical.

[0066] Typically, the variable domains of the heavy and light chains contain three hypervariable regions, also known as complementarity determining regions (CDRs), which are located within relatively conserved framework regions (FRs). The CDRs are typically aligned by the framework regions such that binding to a specific epitope is enabled. Typically, from the N-terminus to the C-terminus, the light and heavy chain variable domains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The amino acids assigned to each domain are typically defined according to the following: Sequences of Proteins of Immunological Interest, Kabat et al.; National Institutes of Health, Bethesda, Md.; 5th ed.; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia et al., (1987) J. Mol. Biol. 196:901-917 or Chothia et al., (1989) Nature 342:878-883.

[0067] As used herein, the term "hypervariable region" refers to the amino acid residues in an antibody that are responsible for antigen binding. The hypervariable regions include amino acid residues from "complementary determining regions" or "CDRs" (i.e., residues 24-34 (CDRL1), 50-56 (CDRL2), and 89-97 (CDRL3) in the light chain variable domain and residues 31-35 (CDRH1), 50-65 (CDRH2), and 95-102 (CDRH3) in the heavy chain variable domain; Kabat et al., (1991) Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, Md.) and / or residues from "hypervariable loops" (i.e., residues 26-32 (CDRL1), 50-52 (CDRL2), and 91-96 (CDRL3) in the light chain variable domain and 26-32 (CDRH1), 53-55 (CDRH2), and 96-101 (CDRH3) in the heavy chain variable domain; Chothia and Lesk, (1987) J. Mol. Biol. 196:901-917). CDRs can also be identified with reference to the IMGT system, which is described in Lefranc MP. Unique database numbering system for immunogenetic analysis. Immunol Today (1997) 18:509. As used herein, the term "framework" or "FR" residues refers to those variable domain residues other than the hypervariable region residues defined herein as CDR residues. The CDRs provide most of the contact residues for antibody binding to an antigen or epitope. The CDRs of interest can be derived from donor antibody variable heavy and light chain sequences and include analogs of naturally occurring CDRs that also share or retain the same antigen binding specificity and / or neutralizing capacity as the donor antibody from which they are derived.

[0068] As used herein, "specifically binds" or "immunologically specifically binds" or "immunologically binds specifically" means that an antibody binds to a predetermined antigen with a much higher affinity than to another antigen(s) (e.g., selectively binds to the active form of complement component C1s as compared to the inactive C1s, which can also be referred to as proC1s zymogen). In some embodiments, the antibody binds to the predetermined antigen with a dissociation constant (K -7 d) of 10 D M or lower, and this K D is at least two-fold lower than its K D for binding to a non-specific antigen (e.g., BSA, casein, or another non-specific polypeptide).

[0069] The phrases "antibody that recognizes C1s" and "antibody specific for C1s" are used interchangeably herein with the term "antibody that immunospecifically binds to C1s". In some embodiments, the antibody specifically or preferentially binds to C1s, such as the active form of C1s rather than other proteins, such as (but not limited to) the inactive form of C1s (proC1). The degree of specificity required of the anti-C1s antibody can depend on the intended use of the antibody, and any rate is defined by its suitability for the intended purpose. In some embodiments, the antibody or binding compound derived from the antigen-binding site of the antibody in the methods encompassed herein binds to its antigen (active form of C1s) with an affinity that is at least two-fold greater, at least ten-fold greater, at least 20-fold greater, or at least 100-fold greater than the affinity for any other antigen, including but not limited to inactive C1s.

[0070] Methods for determining mAb specificity and affinity by competitive inhibition are found in Harlow et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., (1988), Colligan et al., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1992, 1993), and Muller, Meth. Enzymol. 92:589 - 601 (1983), which references are incorporated herein by reference in their entirety.

[0071] The term "homolog" means a protein sequence that has between 40% and 100% sequence homology or identity with a reference sequence. The percent identity between two peptide chains can be determined by pairwise alignment using the default settings of the AlignX module of VectorNTI v.9.0.0 (Invitrogen, Carlsbad, Calif.) or other suitable alignment software such as BLAST. In some embodiments, the antibody or its antigen-binding fragment has at least 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology or identity with the sequences described herein. In some embodiments, the antibody has conservative substitutions compared to the sequences described herein. Exemplary conservative substitutions are illustrated in Table 1 and are within the scope of the disclosed subject matter. Conservative substitutions can be present in the framework region or in the antigen-binding site, provided that they do not adversely affect the properties of the antibody. Substitutions can be made to improve antibody properties such as stability or affinity. Conservative substitutions will result in molecules having functional and chemical characteristics similar to those of the molecules in which such modifications are made. Exemplary amino acid substitutions are shown in the table below.

[0072] Table 1

[0073]

[0074] In some embodiments, variants of the proteins and peptides provided herein are provided. In some embodiments, the variant comprises a substitution, deletion, or insertion. In some embodiments, the variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) substitutions. As described herein, the substitution can be a conservative substitution. In some embodiments, the substitution is non-conservative. In some embodiments, the variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) deletions. In some embodiments, the variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) insertions. In some embodiments, the substitution, deletion, or insertion is present in the CDRs provided herein. In some embodiments, the substitution, deletion, or insertion is not present in the CDRs provided herein.

[0075] As used herein, the term "in combination with" means that the agents can be administered to an animal or subject together (simultaneously as a single agent) in a mixture or sequentially as a single agent in any order.

[0076] The term "epitope" means any molecular moiety capable of being recognized and bound by an antibody at one or more sites in the antigen-binding region of the Ab. Epitopes are usually composed of the chemically reactive surface groups of a molecule such as amino acids or sugar side chains, and have specific three-dimensional structural features as well as specific charge characteristics.

[0077] The term "expression vector" refers to a vector containing a recombinant polynucleotide comprising an expression control sequence operably linked to a nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression; other elements for expression may be supplied by the host cell or in an in vitro expression system. Expression vectors include all expression vectors known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses and adeno-associated viruses) incorporating recombinant polynucleotides.

[0078] In some embodiments, the antibody is a monoclonal antibody that binds to C1s. The sequence of active C1s is as follows (SEQ ID NO:258): residues 1-15 (SEQ ID NO:259) constitute a signal peptide that is cleaved during translation, while residues 16-688 (SEQ ID NO:260) constitute the mature protein, as shown below

[0079] MWCIVLFSLLAWVYAEPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKCVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQENSTPRED(SEQ ID NO:258);

[0080] MWCIVLFSLLAWVYA(SEQ ID NO:259);

[0081] EPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKCVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQE NSTPRED(SEQ ID NO:260).

[0082] The difference between inactive C1s and active C1s is that inactive proC1s cleaves at the peptide bond between R437 and I438 and undergoes a conformational change. The two fragments resulting from this cleavage remain associated via a disulfide bond. Without wishing to be bound by a particular theory, proC1s is a single-chain 86,000 Da protein of the native form of the C1s protein (e.g., a serine protease). C1s is a subunit of the C1 complex, which is the first complement component in a cascade called the classical complement pathway. ProC1s is an inactive zymogen until C1 is activated. The C1 complex binds to and is activated by an antigen-antibody complex (immune complex) that generates the C1r enzyme. The C1r enzyme in the C1 complex activates proC1s to generate the C1s enzyme. The C1 complex is a non-covalent calcium-dependent complex containing one C1q molecule, two C1r molecules, and two C1s molecules. C1q binds to the Fc domain of IgG or IgM via two or more of its six arms. Binding of multiple arms to the immune complex leads to activation of the two C1r proteins (protease zymogens) in the complex to generate two proteases that cleave and activate the two proC1s in the complex (Morikis, D. and Lambris, J.D. (2005)). This activation of proC1s results in cleavage into a two-chain C1s enzyme with 58,000 and 28,000 Dalton fragments.

[0083] In some embodiments, the antibodies provided herein do not inhibit or significantly inhibit protease cleavage of non-complement substrates. Examples of non-complement substrates include, but are not limited to, collagen, HMC I, HMGB1, IGFBP5, LRP6, NCL, and NPM1. Without being bound by any theory, such substrates are important in the clearance of antigens on apoptotic cells or in blood clotting in bone, muscle, and connective tissue. Thus, antibodies that do not inhibit or significantly inhibit protease cleavage of non-complement substrates, such as the antibodies provided herein, may allow the antibodies to be utilized with fewer side effects or at higher doses. In some embodiments, the non-complement substrate is collagen. In some embodiments, the non-complement substrate is HMC I. In some embodiments, the non-complement substrate is HMGB1. In some embodiments, the non-complement substrate is IGFBP5. In some embodiments, the non-complement substrate is LRP6. In some embodiments, the non-complement substrate is NCL. In some embodiments, the non-complement substrate is NPM1.

[0084] In some embodiments, the antibody comprises an Fc domain. The Fc domain may be linked to the heavy or light chain of the antibody. In some embodiments, the Fc domain comprises a mutation to extend the half-life of the antibody. In some embodiments, the Fc domain comprises a mutation, such as the mutation described in U.S. Patent No. 7,670,600, which is incorporated herein by reference in its entirety. In some embodiments, the constant region comprises a mutation at the position corresponding to amino acid residue 428 of the wild-type human IgG constant domain, which position is numbered according to the Kabat EU numbering index ("EU numbering"). Without being limited to any particular theory, an antibody comprising a mutation corresponding to residue 428 may have an extended half-life compared to the half-life of an IgG having a wild-type human IgG constant domain. In some embodiments, the mutation is a substitution of the native residue with threonine, leucine, phenylalanine, or serine. In some embodiments, the antibody further comprises one or more amino acid substitutions relative to the corresponding wild-type human IgG constant domain at one or more of amino acid residues 251-256, 285-290, 308-314, 385-389, and 429-436, which amino acid residues are numbered according to the Kabat EU numbering index. Specific mutations or substitutions at these positions are described in U.S. Patent No. 7,670,600, which is incorporated herein by reference in its entirety.

[0085] Other mutations may be used in the Fc domain, such as the mutations provided in U.S. Patent No. 8,394,925, which is incorporated herein by reference in its entirety. In some embodiments, the Fc region is a variant Fc region comprising amino acid substitutions at positions 428 and 434, wherein the amino acid substitutions are leucine, a non-wild-type amino acid at position 428, and serine, a non-wild-type amino acid at position 434, wherein the polypeptide is an antibody and wherein the numbering is according to the EU index of Kabat et al. In some embodiments, the Fc region comprises an S228P, L235E, M428L, or N434S substitution. In some embodiments, the Fc region comprises an M428L substitution. In some embodiments, the Fc region comprises an N434S substitution. In some embodiments, the Fc region comprises M428L and N434S substitutions (EU numbering), which may be collectively referred to as "LS mutation" or "LS". In some embodiments, the Fc region comprises an M252Y, S254T, and / or T256E substitution (EU numbering). In some embodiments, the Fc region comprises M252Y, S254T, and T256E substitutions. When all three M252Y, S254T, and T256E mutations are present in the Fc region, it may be referred to as "YTE" or "YTE mutation".

[0086] In some embodiments, the antibody comprises a constant region as described below with or without the mutations provided in the following list:

[0087] >IgG4 S228P L235E LS

[0088] ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVLHEALHSHYTQKSLSLSLGK(SEQ ID NO:261);

[0089] >IgG4 S228P L235E YTE

[0090] ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK(SEQ ID NO:262).

[0091] In some embodiments, the antibody comprises a constant region as provided herein, wherein the C-terminal lysine (K) amino acid has been deleted. In some embodiments, the antibody comprises a constant region as set forth below:

[0092] >IgG4 S228P L235E LS-truncated

[0093] ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVLHEALHSHYTQKSLSLSLG(SEQ ID NO:263);

[0094] >IgG4 S228P L235E YTE-truncated

[0095] ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS VMHEALHNHYTQKSLSLSLG(SEQ ID NO:264).

[0096] In some embodiments, the antibody (such as the light chain) comprises a κ constant region (such as a human constant domain), which may comprise the following sequence:

[0097] RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (human κ constant domain, SEQ ID NO:265).

[0098] As used herein and unless otherwise specified, the term "about" is intended to mean ±5% of the value it modifies. Thus, about 100 means 95 to 105.

[0099] In some embodiments, the presence of an antigen is detected using the antibodies described herein. The antibodies of the invention can be used in any device or method for detecting the presence of an antigen. In some embodiments, the antibody is used to detect the active form of C1s. In some embodiments, the antibody is used to preferentially (specifically) detect the active form of C1s rather than the inactive form.

[0100] The term "purified" with reference to an antibody means an antibody that is substantially free of other materials that are associated with the molecule in its natural environment. For example, a purified protein is substantially free of cellular material or other proteins from the cells or tissues from which it is derived. The term refers to a preparation in which the purity of the isolated protein is sufficient for analysis or is at least 70% to 80% (w / w) pure, at least 80%-90% (w / w) pure, 90-95% pure; and at least 95%, 96%, 97%, 98%, 99% or 100% (w / w) pure. In some embodiments, the antibody is purified.

[0101] Antibody conjugate

[0102] The antibodies provided herein can also be conjugated to a chemical moiety. The chemical moiety can in particular be a polymer, a radionuclide, or a cytotoxic agent. In some embodiments, this can be referred to as an antibody-drug conjugate. In some embodiments, the chemical moiety is a polymer that extends the half-life of the antibody molecule in a subject. Suitable polymers include, but are not limited to, polyethylene glycol (PEG) (e.g., PEG having a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa, or 40 kDa), dextran, and monomethoxypolyethylene glycol (mPEG). Lee et al., (1999) (Bioconj. Chem. 10:973-981) disclose PEG-conjugated single-chain antibodies. Wen et al., (2001) (Bioconj. Chem. 12:545-553) disclose conjugated antibodies having PEG attached to a radiometal chelator (diethylenetriaminepentaacetic acid (DTPA)). Examples of chemical moieties include, but are not limited to, mitotic inhibitors such as calicheamicin (e.g., ozogamicin), monomethyl auristatin E, mertansine, and analogs. Other examples include, but are not limited to, bioactive antimicrotubule agents, alkylating agents, and DNA minor groove binders. Other examples are provided herein and below. The chemical moiety can be linked to the antibody via a linking group (maleimide), a cleavable linker (such as a cathepsin-cleavable linker (valine-citrulline)), and in some embodiments one or more spacers (e.g., p-aminobenzyl carbamate).

[0103] The antibodies and antibody fragments of the invention can also be conjugated to labels such as: 99 Tc, 90 Y, 111In, 32 P, 14 C, 125 I, 3 H, 131 I, 11 C, 15 O, 13 N, 18 F, 35 S, 51 Cr, 57 To, 226 Ra, 60Co, 59 Fe, 57 Se, 152 Eu, 67 CU, 217 Ci, 211 At, 212 Pb, 47 Sc, 109 Pd, 234 Th, and 40K,157 Gd, 55 Mn, 52 Tr, and 56 Fe.

[0104] Antibodies and antibody fragments can also be conjugated to fluorescent or chemiluminescent labels, which include fluorophores such as rare earth chelates, fluorescein and its derivatives, rhodamine and its derivatives, isothiocyanates, phycoerythrin, phycocyanin, allophycocyanin, o-phthalaldehyde, fluorescamine, 152 Eu, dansyl, umbelliferone, luciferin, luminal label, isoluminal label, aromatic acridinium ester label, imidazole label, acridinium salt label, oxalate ester label, aequorin label, 2,3-dihydrophthalazinedione, biotin / avidin, spin labels, and stable free radicals.

[0105] Antibody molecules can also be conjugated to cytotoxic agents such as diphtheria toxin, Pseudomonas aeruginosa exotoxin A chain, ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii protein and compounds (e.g., fatty acids), saponin, Phytolacca americana proteins PAPI, PAPII, and PAP-S, momordica charantia inhibitor, curcin, croton toxin, saponaria officinalis inhibitor, mitogens, restrictocin, phenomycin, and enomycin.

[0106] Any method known in the art for conjugating the antibody molecules of the invention to the respective moieties can be employed, including those described by Hunter et al., (1962) Nature 144:945; David et al., (1974) Biochemistry 13:1014; Pain et al., (1981) J. Immunol. Methods 40:219; and Nygren, J., (1982) Histochem. and Cytochem. 30:407. Methods for conjugating antibodies are well known and well established in the art.

[0107] In some embodiments, antibodies (e.g., anti-C1s) are provided herein. In some embodiments, the antibody is a recombinant antibody that binds to C1s. In some embodiments, the antibody binds to the active form of C1s. In some embodiments, the antibody preferentially binds to the active form of C1s rather than the inactive form. In some embodiments, the antibody binds to its active form with an affinity that is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or 200% higher than its affinity for the inactive form of C1s. In some embodiments, the C1s protein is a human C1s protein, such as the active form of C1s. In some embodiments, the antibody does not specifically bind to the inactive form of the C1s protein. As used herein, the term "recombinant antibody" refers to an antibody that is not naturally occurring. In some embodiments, the term "recombinant antibody" refers to an antibody that is not isolated from a human subject. In some embodiments, the antibody binds to the active form of C1s with an affinity that is at least 100-fold higher than that for proC1s.

[0108] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the following table and its CDRs are described according to Kabat numbering.

[0109] Table 2:

[0110]

[0111]

[0112]

[0113]

[0114]

[0115]

[0116] The CDRs in the above table can also be represented according to Chothia CDR or IMGT CDR. Different antibodies are described in the following table.

[0117] Table 3:

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124] Table 4:

[0125]

[0126]

[0127]

[0128]

[0129]

[0130] In some embodiments, the antibody comprises a variable heavy chain that comprises HCDR1 of SEQ ID NO:128, HCDR2 of SEQ ID NO:129, and HCDR3 of DEQLGGX1X2YYYYYMDX3 (SEQ ID NO:333), wherein:

[0131] X1 is N, T, I, Q, L, K or R;

[0132] X2 is Y, T, K, H or V; and

[0133] X3 is V or A.

[0134] In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is Y, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is Y, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is T, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is T, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is K, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is K, and X3 is A.

[0135] In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is H, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is H, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is V, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is V, and X3 is A. In some embodiments, X1 is N, X2 is Y, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is T, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is T, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is K, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is K, and X3 is A.

[0136] In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is H, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is H, and X3 is A. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is V, and X3 is V. In some embodiments, X1 is N, T, I, Q, L, K or R, X2 is V, and X3 is A. In some embodiments, X1 is not N. In some embodiments, X1 is not T. In some embodiments, X1 is not I. In some embodiments, X1 is not Q. In some embodiments, X1 is not L. In some embodiments, X1 is not K. In some embodiments, X1 is not R.

[0137] In some embodiments, an antibody is provided that comprises a variable light chain LCDR1 of SEQ ID NO:106, an LCDR2 of SEQ ID NO:107, and an LCDR3 comprising the amino acid sequence:

[0138] X4QX5X6X7X8PLX9 (SEQ ID NO:332),

[0139] X4 is L or F;

[0140] X5 is Y or T;

[0141] X6 is N, K, A, H or R;

[0142] X7 is S, Q, I or A;

[0143] X8 is Y, V or H; and

[0144] X9 is T, G, K, R, I or A.

[0145] In some embodiments, X4 is L; X5 is Y or T; X6 is N, K, A, H, or R; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y; X6 is N, K, A, H, or R; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is T; X6 is N, K, A, H, or R; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is K; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is A; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is H; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is R; X7 is S, Q, I, or A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is S; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is Q; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is I; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is A; X8 is Y, V, or H; and X9 is T, G, K, R, I, or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H, or R; X7 is S, Q, I, or A; X8 is Y; and X9 is T, G, K, R, I, or A.In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is V; and X9 is T, G, K, R, I or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is H; and X9 is T, G, K, R, I or A. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is T. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is G. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is K. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is R. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is I. In some embodiments, X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is A.

[0146] In some embodiments, an antibody is provided that comprises a variable heavy chain comprising an HCDR1 of SEQ ID NO:128, an HCDR2 of SEQ ID NO:129, and an HCDR3 of DEQLGGX1X2YYYYYMDX3 (SEQ ID NO:333), wherein X1 is N, T, I, Q, L, K or R; X2 is Y, T, K, H or V; and X3 is V or A; and a variable light chain comprising an LCDR1 of SEQ ID NO:106, an LCDR2 of SEQ ID NO:107, and an LCDR3 comprising the amino acid sequence X4QX5X6X7X8PLX9 (SEQ ID NO:332), wherein X4 is L or F; X5 is Y or T; X6 is N, K, A, H or R; X7 is S, Q, I or A; X8 is Y, V or H; and X9 is T, G, K, R, I or A. In some embodiments, the mutations of HCDR3 and LCDR3 are as described above.

[0147] In some embodiments, the antibody comprises a variable light chain and a heavy chain as shown in MAB21, MAB22, MAB23, MAB24, MAB25, MAB26, MAB27, MAB28, MAB29, MAB30, MAB51, MAB52, MAB53, MAB54, MAB55, MAB56, MAB57, MAB58, MAB59 or MAB60, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO: 333 and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 332 as described herein. In some embodiments, the antibody comprises a variable light chain and a heavy chain, each independently at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the VL and VH of MAB21, MAB22, MAB23, MAB24, MAB25, MAB26, MAB27, MAB28, MAB29, MAB30, MAB51, MAB52, MAB53, MAB54, MAB55, MAB56, MAB57, MAB58, MAB59 or MAB60, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO: 333 and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 332 as described herein.

[0148] In some embodiments, the antibody does not comprise an HCDR3 consisting of EQLGGNYYYYYYMDV and / or an LCDR3 consisting of LQYNSYPLT. In some embodiments, when the antibody comprises an HCDR3 consisting of EQLGGNYYYYYYMDV, the antibody does not comprise an LCDR3 consisting of LQYNSYPLT.

[0149] In some embodiments, the antibody comprises a variable heavy chain comprising an HCDR1 of SEQ ID NO: 61, an HCDR2 of SEQ ID NO: 62, and DX 10 X 11 X 12 YX 13 X 14 DX 15 (SEQ ID NO: 329) of HCDR3, wherein: X 10 is E, Q or N; X 11 is T, E, S or N; X 12 is D or Q; X 13 is A or G; X 14 is L, W, F or Y; and X 15 is Y, E, L, N, F or W. In some embodiments, X10 is E. In some embodiments, X 10 is Q. In some embodiments, X 10 is N. In some embodiments, X 11 is T. In some embodiments, X 11 is E. In some embodiments, X 11 is S. In some embodiments, X 11 is N. In some embodiments, X 12 is D. In some embodiments, X 12 is D. In some embodiments, X 13 is A. In some embodiments, X 13 is G. In some embodiments, X 14 is L. In some embodiments, X 14 is W. In some embodiments, X 14 is F. In some embodiments, X 14 is or Y. In some embodiments, X 15 is Y. In some embodiments, X 15 is E. In some embodiments, X 15 is L. In some embodiments, X 15 is N. In some embodiments, X 15 is F. In some embodiments, X 15 is W.

[0150] In some embodiments, the antibody comprises a variable light chain that comprises LCDR1 of SEQ ID NO:64, LCDR2 of SEQ ID NO:65, and an LCDR3 comprising the amino acid sequence X 16 X 17 X 18 EDX 19 X 20 X 21 X 22 (SEQ ID NO:328), wherein X 16 is Q, E, K or H; X 17 is Q or H; X 18 is Y or H, X 19 is L or Y; X 20 is P or I; X 21 is L or P, and X 22 is T or V. In some embodiments, X 16 is Q. In some embodiments, X 16 is E. In some embodiments, X 16 is K. In some embodiments, X 16is H. In some embodiments, X 17 is Q. In some embodiments, X 17 is H. In some embodiments, X 18 is Y. In some embodiments, X 18 is H. In some embodiments, X 19 is L. In some embodiments, X 19 is Y. In some embodiments, X 20 is P. In some embodiments, X 20 is I. In some embodiments, X 21 is L. In some embodiments, X 21 is P. In some embodiments, X 22 is T. In some embodiments, X 22 is V.

[0151] In some embodiments, an antibody is provided that comprises a variable heavy chain comprising HCDR1 of SEQ ID NO:61, HCDR2 of SEQ ID NO:62, and HCDR3 of SEQ ID NO:329 as described herein, and a variable light chain comprising LCDR1 of SEQ ID NO:63, LCDR2 of SEQ ID NO:64, and LCDR3 comprising the amino acid sequence of SEQ ID NO:328 as described herein.

[0152] In some embodiments, the antibody comprises a variable light chain and a heavy chain as shown by MAB1, MAB2, MAB3, MAB4, MAB5, MAB6, MAB7, MAB8, MAB9, MAB10, MAB31, MAB32, MAB33, MAB34, MAB35, MAB36, MAB38, MAB39 or MAB40, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO: 329 and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 328 as described herein. In some embodiments, the antibody comprises a variable light chain and a heavy chain, each independently being at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the VL and VH of MAB1, MAB2, MAB3, MAB4, MAB5, MAB6, MAB7, MAB8, MAB9, MAB10, MAB31, MAB32, MAB33, MAB34, MAB35, MAB36, MAB38, MAB39 or MAB40, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO: 329 and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 328 as described herein.

[0153] In some embodiments, a VH and a VL are provided, provided that when the HCDR3 is DETDYALDY, the LCDR3 is not QQYEDLPLT. In some embodiments, SEQ ID NO: 329 is not DETDYALDY. In some embodiments, SEQ ID NO: 328 is not QQYEDLPLT.

[0154] In some embodiments, the antibody comprises an HCDR1 comprising SEQ ID NO: 82, an HCDR2 comprising SEQ ID NO: 83, and X 23 GX 24 X 25 X 26 X 27 PX 28 X 29 X 30Variable heavy chain of the HCDR3 of (SEQ ID NO:330), wherein: X23 is E or K, X24 is L or E; X25 is A or G, X26 is G or W, X27 is R, V, L, I or F, X28 is F, Y or T, X29 is D or Y, and X30 is A, V, L, S, H or I. In some embodiments, X23 is E. In some embodiments, X24 is L. In some embodiments, X25 is A. In some embodiments, X26 is G. In some embodiments, X27 is R. In some embodiments, X27 is V. In some embodiments, X27 is L. In some embodiments, X27 is I. In some embodiments, X27 is F. In some embodiments, X28 is F. In some embodiments, X28 is Y. In some embodiments, X29 is D. In some embodiments, X30 is S or L.

[0155] In some embodiments, the antibody comprises a variable light chain that comprises the LCDR1 of SEQ ID NO:85, the LCDR2 of SEQID NO:86, and X 31 QX 32 X 33 SX 34 X 35 X 36 X 37 (SEQ ID NO:331) of the LCDR3, wherein X31 is Q or V; X32 is Y, A, V or H; X33 is N, P, S or R; X34 is Y, L, or P; X35 is S, K, V, A, D or R; X36 is W or L; and X37 is T or L. In some embodiments, X31 is Q. In some embodiments, X31 is V. In some embodiments, X32 is Y. In some embodiments, X32 is A. In some embodiments, X32 is V. In some embodiments, X32 is H. In some embodiments, X33 is N. In some embodiments, X33 is P. In some embodiments, X33 is S. In some embodiments, X33 is R. In some embodiments, X34 is Y. In some embodiments, X34 is L. In some embodiments, X34 is P. In some embodiments, X35 is S. In some embodiments, X35 is K. In some embodiments, X35 is V. In some embodiments, X35 is A. In some embodiments, X35 is D. In some embodiments, X35 is R. In some embodiments, X36 is W. In some embodiments, X36 is L. In some embodiments, X37 is T. In some embodiments, X37 is L.

[0156] In some embodiments, an antibody is provided that comprises a variable heavy chain comprising HCDR1 of SEQ ID NO:82, HCDR2 of SEQ ID NO:83, and HCDR3 of SEQ ID NO:330 as described herein, and a variable light chain comprising LCDR1 of SEQ ID NO:84, LCDR2 of SEQ ID NO:85, and LCDR3 comprising the amino acid sequence of SEQ ID NO:331 as described herein.

[0157] In some embodiments, the antibody comprises a variable light chain and heavy chain as shown in MAB11, MAB12, MAB13, MAB14, MAB15, MAB16, MAB17, MAB18, MAB19, MAB20, MAB41, MAB42, MAB43, MAB44, MAB45, MAB46, MAB47, MAB48, MAB49 or MAB50, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO:330 and the LCDR3 comprises the amino acid sequence of SEQ ID NO:331 as described herein. In some embodiments, the antibody comprises a variable light chain and heavy chain that are each independently at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of VL and VH of MAB11, MAB12, MAB13, MAB14, MAB15, MAB16, MAB17, MAB18, MAB19, MAB20, MAB41, MAB42, MAB43, MAB44, MAB45, MAB46, MAB47, MAB48, MAB49 or MAB50, provided that the HCDR3 comprises the amino acid sequence of SEQ ID NO:330 and the LCDR3 comprises the amino acid sequence of SEQ ID NO:331 as described herein.

[0158] In some embodiments, a VH and VL are provided, provided that when the HCDR3 is EGLAGRPFDS, the LCDR3 is not QQYNSYSWTY. In some embodiments, SEQ ID NO:330 is not EGLAGRPFDS. In some embodiments, SEQ ID NO:331 is not QQYNSYSWTY.

[0159] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy or light chain CDR provided in the above table. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain LCDR having the sequence of SEQ ID NO: 64, 65, 66, 68, 71, 75, 77, 79, 81, 85, 86, 87, 89, 92, 94, 95, 97, 99, 101, 102, 106, 107, 108, 110, 112, 113, 115, 118, 119, 121, 123, 133, 134, 147, 148, 159, 160 or a combination thereof. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain HCDR having the sequence of SEQ ID NO: 61, 62, 63, 67, 69, 70, 72, 73, 74, 76, 78, 80, 82, 83, 84, 88, 90, 91, 93, 96, 98, 100, 103, 104, 105, 109, 111, 114, 116, 117, 120, 122, 124, 125, 126, 127, 128, 129, 130, 131, 132, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 161, 162, 163, 164, 165, 166, 167 or a combination thereof.

[0160] In some embodiments, the sequence of the heavy chain HCDR comprises a combination of one or more of the following: SEQ ID NO: 61, 62, 63, 67, 69, 70, 72, 73, 74, 76, 78, 80, 82, 83, 84, 88, 90, 91, 93, 96, 98, 100, 103, 104, 105, 109, 111, 114, 116, 117, 120, 122, 124, 125, 126, 127, 128, 129, 130, 131, 132, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 161, 162, 163, 164, 165, 166 and 167.

[0161] It should be understood that the CDRs cited in the embodiments described in this specification can be interchanged with CDRs having different formats (such as Chothia and IMGT) characteristics as shown in the above table.

[0162] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:66.

[0163] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:68.

[0164] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:71.

[0165] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:75.

[0166] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:77.

[0167] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:79.

[0168] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:64, the LCDR2 has the sequence of SEQ ID NO:65, and the LCDR3 has the sequence of SEQ ID NO:81.

[0169] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:87.

[0170] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:89.

[0171] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:92.

[0172] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:94.

[0173] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:95.

[0174] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:97.

[0175] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:99.

[0176] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:101.

[0177] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:85, the LCDR2 has the sequence of SEQ ID NO:86, and the LCDR3 has the sequence of SEQ ID NO:102.

[0178] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:106, the LCDR2 has the sequence of SEQ ID NO:107, and the LCDR3 has the sequence of SEQ ID NO:108.

[0179] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:106, the LCDR2 has the sequence of SEQ ID NO:107, and the LCDR3 has the sequence of SEQ ID NO:110.

[0180] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 112.

[0181] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 113.

[0182] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 115.

[0183] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 118.

[0184] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 119.

[0185] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 121.

[0186] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 106, the LCDR2 has the sequence of SEQ ID NO: 107, and the LCDR3 has the sequence of SEQ ID NO: 123.

[0187] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 133, the LCDR2 has the sequence of SEQ ID NO: 134, and the LCDR3 has the sequence of SEQ ID NO: 66.

[0188] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 133, the LCDR2 has the sequence of SEQ ID NO: 134, and the LCDR3 has the sequence of SEQ ID NO: 68.

[0189] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 133, the LCDR2 has the sequence of SEQ ID NO: 134, and the LCDR3 has the sequence of SEQ ID NO: 71.

[0190] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 133, the LCDR2 has the sequence of SEQ ID NO: 134, and the LCDR3 has the sequence of SEQ ID NO: 75.

[0191] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 133, the LCDR2 has the sequence of SEQ ID NO: 134, and the LCDR3 has the sequence of SEQ ID NO: 77.

[0192] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:133, the LCDR2 has the sequence of SEQ ID NO:134, and the LCDR3 has the sequence of SEQ ID NO:79.

[0193] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:133, the LCDR2 has the sequence of SEQ ID NO:134, and the LCDR3 has the sequence of SEQ ID NO:81.

[0194] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:147, the LCDR2 has the sequence of SEQ ID NO:148, and the LCDR3 has the sequence of SEQ ID NO:87.

[0195] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:147, the LCDR2 has the sequence of SEQ ID NO:148, and the LCDR3 has the sequence of SEQ ID NO:89.

[0196] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:147, the LCDR2 has the sequence of SEQ ID NO:148, and the LCDR3 has the sequence of SEQ ID NO:92.

[0197] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:147, the LCDR2 has the sequence of SEQ ID NO:148, and the LCDR3 has the sequence of SEQ ID NO:94.

[0198] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 147, the LCDR2 has the sequence of SEQ ID NO: 148, and the LCDR3 has the sequence of SEQ ID NO: 95.

[0199] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 147, the LCDR2 has the sequence of SEQ ID NO: 148, and the LCDR3 has the sequence of SEQ ID NO: 97.

[0200] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 147, the LCDR2 has the sequence of SEQ ID NO: 148, and the LCDR3 has the sequence of SEQ ID NO: 99.

[0201] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 147, the LCDR2 has the sequence of SEQ ID NO: 148, and the LCDR3 has the sequence of SEQ ID NO: 101.

[0202] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 147, the LCDR2 has the sequence of SEQ ID NO: 148, and the LCDR3 has the sequence of SEQ ID NO: 102.

[0203] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 159, the LCDR2 has the sequence of SEQ ID NO: 160, and the LCDR3 has the sequence of SEQ ID NO: 108.

[0204] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of SEQ ID NO:110.

[0205] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of SEQ ID NO:112.

[0206] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of EQ ID NO:113.

[0207] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of SEQ ID NO:115.

[0208] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of SEQ ID NO:118.

[0209] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO:159, the LCDR2 has the sequence of SEQ ID NO:160, and the LCDR3 has the sequence of SEQ ID NO:119.

[0210] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 159, the LCDR2 has the sequence of SEQ ID NO: 160, and the LCDR3 has the sequence of SEQ ID NO: 112.

[0211] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a light chain variable region having an LCDR1, an LCDR2, and an LCDR3, wherein the LCDR1 has the sequence of SEQ ID NO: 159, the LCDR2 has the sequence of SEQ ID NO: 160, and the LCDR3 has the sequence of SEQ ID NO: 123.

[0212] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO: 61, the HCDR2 has the sequence of SEQ ID NO: 62, and the HCDR3 has the sequence of SEQ ID NO: 63.

[0213] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO: 61, the HCDR2 has the sequence of SEQ ID NO: 62, and the HCDR3 has the sequence of SEQ ID NO: 67.

[0214] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO: 61, the HCDR2 has the sequence of SEQ ID NO: 62, and the HCDR3 has the sequence of SEQ ID NO: 69.

[0215] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO: 61, the HCDR2 has the sequence of SEQ ID NO: 62, and the HCDR3 has the sequence of SEQ ID NO: 70.

[0216] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:72.

[0217] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:73.

[0218] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:74.

[0219] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:76.

[0220] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:78.

[0221] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:61, the HCDR2 has the sequence of SEQ ID NO:62, and the HCDR3 has the sequence of SEQ ID NO:80.

[0222] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:84.

[0223] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:88.

[0224] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:90.

[0225] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:91.

[0226] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:93.

[0227] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:96.

[0228] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:98.

[0229] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:82, the HCDR2 has the sequence of SEQ ID NO:83, and the HCDR3 has the sequence of SEQ ID NO:100.

[0230] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:105.

[0231] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:109.

[0232] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:111.

[0233] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:114.

[0234] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:116.

[0235] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:117.

[0236] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:120.

[0237] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:103, the HCDR2 has the sequence of SEQ ID NO:104, and the HCDR3 has the sequence of SEQ ID NO:122.

[0238] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:63.

[0239] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:67.

[0240] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:69.

[0241] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:70.

[0242] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:72.

[0243] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:73.

[0244] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:74.

[0245] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:76.

[0246] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:78.

[0247] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:124, the HCDR2 has the sequence of SEQ ID NO:125, and the HCDR3 has the sequence of SEQ ID NO:80.

[0248] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:84.

[0249] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:88.

[0250] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:90.

[0251] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:91.

[0252] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:93.

[0253] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:96.

[0254] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:98.

[0255] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:126, the HCDR2 has the sequence of SEQ ID NO:127, and the HCDR3 has the sequence of SEQ ID NO:100.

[0256] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:105.

[0257] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:109.

[0258] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:111.

[0259] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:114.

[0260] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:116.

[0261] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:117.

[0262] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:120.

[0263] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:128, the HCDR2 has the sequence of SEQ ID NO:129, and the HCDR3 has the sequence of SEQ ID NO:122.

[0264] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:132.

[0265] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:135.

[0266] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:136.

[0267] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:137.

[0268] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:138.

[0269] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:139.

[0270] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:140.

[0271] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:141.

[0272] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:142.

[0273] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:130, the HCDR2 has the sequence of SEQ ID NO:131, and the HCDR3 has the sequence of SEQ ID NO:143.

[0274] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:146.

[0275] In some embodiments, the antibody or an antibody-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:149.

[0276] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:150.

[0277] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:151.

[0278] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:152.

[0279] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:153.

[0280] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:154.

[0281] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:144, the HCDR2 has the sequence of SEQ ID NO:145, and the HCDR3 has the sequence of SEQ ID NO:155.

[0282] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:158.

[0283] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:161.

[0284] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:162.

[0285] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:163.

[0286] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:164.

[0287] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:165.

[0288] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:166.

[0289] In some embodiments, the antibody or an antigen-binding fragment thereof comprises a heavy chain variable domain having an HCDR1, an HCDR2, and an HCDR3, wherein the HCDR1 has the sequence of SEQ ID NO:156, the HCDR2 has the sequence of SEQ ID NO:157, and the HCDR3 has the sequence of SEQ ID NO:167.

[0290] In some embodiments, the antibody or an antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:66; and (ii) a heavy chain variable region comprising heavy chain HCDRl, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:63; or variants or conventional equivalents of any of the foregoing.

[0291] In some embodiments, the antibody or an antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:68; and (ii) a heavy chain variable region comprising heavy chain HCDRl, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62, and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:67; or variants or conventional equivalents of any of the foregoing.

[0292] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:68; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:69; or a variant or conventional equivalent of any of the foregoing.

[0293] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62, and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:70; or a variant or conventional equivalent of any of the foregoing.

[0294] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:71; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62, and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:72; or a variant or conventional equivalent of any of the foregoing.

[0295] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:71; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:73; or a variant or conventional equivalent of any of the foregoing.

[0296] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:75; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:74; or a variant or conventional equivalent of any of the foregoing.

[0297] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:77; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:76; or a variant or conventional equivalent of any of the foregoing.

[0298] In some embodiments, an antibody or an antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:79; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:78; or a relative of any of the foregoing.

[0299] In some embodiments, an antibody or an antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:81; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO:61; the HCDR2 has the amino acid sequence of SEQ ID NO:62; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO:80; or a variant or conventional equivalent of any of the foregoing.

[0300] In some embodiments, an antibody or an antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:87; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:84; or a variant or conventional equivalent of any of the foregoing.

[0301] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:89; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:88; or a variant or conventional equivalent of any of the foregoing.

[0302] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:89; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:90; or a variant or conventional equivalent of any of the foregoing.

[0303] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:92; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:91; or a variant or conventional equivalent of any of the foregoing.

[0304] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:94; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:93; or a variant or conventional equivalent of any of the foregoing.

[0305] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:95; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:84; or a variant or conventional equivalent of any of the foregoing.

[0306] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:97; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:96; or a variant or conventional equivalent of any of the foregoing.

[0307] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:99; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:98; or a variant or conventional equivalent of any of the foregoing.

[0308] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:101; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:100; or a variant or conventional equivalent of any of the foregoing.

[0309] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:102; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:100; or a variant or conventional equivalent of any of the foregoing.

[0310] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 108; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 105; or variants or conventional equivalents of any of the foregoing.

[0311] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 110; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 109; or variants or conventional equivalents of any of the foregoing.

[0312] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 112; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 111; or a variant or conventional equivalent of any of the foregoing.

[0313] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 113; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 105; or a variant or conventional equivalent of any of the foregoing.

[0314] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 115; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 114; or a variant or conventional equivalent of any of the foregoing.

[0315] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 113; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 116; or a variant or conventional equivalent of any of the foregoing.

[0316] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 118; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 117; or a variant or conventional equivalent of any of the foregoing.

[0317] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 119; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 116; or a variant or conventional equivalent of any of the foregoing.

[0318] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 121; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 120; or a variant or conventional equivalent of any of the foregoing.

[0319] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 123; and (ii) a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 122; or a variant or conventional equivalent of any of the foregoing.

[0320] Although the foregoing paragraphs may refer to CDRs under the Kabat system, equivalent CDR sequences as designated by IMGT and Chothia may be used.

[0321] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:63, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:63, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:132, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:66, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:66, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:66.

[0322] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:67, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:67, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:135, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:68, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:68, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:68.

[0323] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:69, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:69, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:136, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:68, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:68, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:68.

[0324] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:70, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:70, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:137, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:71.

[0325] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:72, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:72, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:138, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:71.

[0326] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:73, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:73, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:139, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:71, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:71.

[0327] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:74, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:74, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:140, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:75, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:75, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:75.

[0328] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62, and SEQ ID NO:76, respectively selected from SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:76, or respectively selected from SEQ ID NO:130, SEQ ID NO:131, and SEQ ID NO:141, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:77, respectively selected from SEQ ID NO:64, SEQ ID NO:65, and SEQ ID NO:77, or respectively selected from SEQ ID NO:133, SEQ ID NO:134, and SEQ ID NO:77.

[0329] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2 and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62 and SEQ ID NO:78, respectively selected from SEQ ID NO:124, SEQ ID NO:125 and SEQ ID NO:78, or respectively selected from SEQ ID NO:130, SEQ ID NO:131 and SEQ ID NO:142, and the LCDR1, LCDR2 and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65 and SEQ ID NO:79, respectively selected from SEQ ID NO:64, SEQ ID NO:65 and SEQ ID NO:79, or respectively selected from SEQ ID NO:133, SEQ ID NO:134 and SEQ ID NO:79.

[0330] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2 and HCDR3 are respectively selected from SEQ ID NO:61, SEQ ID NO:62 and SEQ ID NO:80, respectively selected from SEQ ID NO:124, SEQ ID NO:125 and SEQ ID NO:80, or respectively selected from SEQ ID NO:130, SEQ ID NO:131 and SEQ ID NO:143, and the LCDR1, LCDR2 and LCDR3 are respectively selected from SEQ ID NO:64, SEQ ID NO:65 and SEQ ID NO:81, respectively selected from SEQ ID NO:64, SEQ ID NO:65 and SEQ ID NO:81, or respectively selected from SEQ ID NO:133, SEQ ID NO:134 and SEQ ID NO:81.

[0331] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:84, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:84, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:146, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:87, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:87, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:87.

[0332] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:88, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:88, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:149, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:89, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:89, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:89.

[0333] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:90, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:90, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:150, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:89, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:89, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:89.

[0334] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:91, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:91, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:151, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:92, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:92, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:92.

[0335] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:93, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:93, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:152, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:94, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:94, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:94.

[0336] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:84, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:84, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:146, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:95, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:95, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:95.

[0337] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:96, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:96, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:153, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:97, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:97, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:97.

[0338] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:98, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:98, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:154, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:99, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:99, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:99.

[0339] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:100, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:100, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:155, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:101, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:101, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:101.

[0340] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO:82, SEQ ID NO:83, and SEQ ID NO:100, respectively selected from SEQ ID NO:126, SEQ ID NO:127, and SEQ ID NO:100, or respectively selected from SEQ ID NO:144, SEQ ID NO:145, and SEQ ID NO:155, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:102, respectively selected from SEQ ID NO:85, SEQ ID NO:86, and SEQ ID NO:102, or respectively selected from SEQ ID NO:147, SEQ ID NO:148, and SEQ ID NO:102.

[0341] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 105, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 105, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 108, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 108, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 108.

[0342] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 109, or respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 109, are respectively the sense strand or the antisense strand 156, SEQ ID NO: 157, and SEQ ID NO: 161, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 110, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 110, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 110.

[0343] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 111, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 111, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 162, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 112, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 112, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 112.

[0344] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 105, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 105, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 113, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 113, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 113.

[0345] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 114, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 114, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 163, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 115, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 115, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 115.

[0346] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 116, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 116, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 164, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 113, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 113, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 113.

[0347] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 117, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 117, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 165, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 118, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 118, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 118.

[0348] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 116, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 116, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 164, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 119, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 119, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 119.

[0349] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 120, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 120, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 166, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 121, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 121, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 121.

[0350] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, wherein the HCDR1, HCDR2, and HCDR3 are respectively selected from SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 122, respectively selected from SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 122, or respectively selected from SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 167, and the LCDR1, LCDR2, and LCDR3 are respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 123, respectively selected from SEQ ID NO: 106, SEQ ID NO: 107, and SEQ ID NO: 123, or respectively selected from SEQ ID NO: 159, SEQ ID NO: 160, and SEQ ID NO: 123.

[0351] In some embodiments, the antibody comprises a heavy chain variable region peptide having one of the following sequences or a variant thereof:

[0352] Table 5:

[0353]

[0354]

[0355]

[0356]

[0357]

[0358]

[0359] In some embodiments, the antibody comprises the following variable heavy chain sequence:

[0360] VQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISRSGSTKYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDENYALDWWGQGTLVTVSS (SEQ ID NO: 454). The variable heavy chain comprising this amino acid sequence pairs with, for example, a variable light chain comprising the amino acid sequence of SEQ ID NO 18 or a light chain of SEQ ID NO: 236. The variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO: 454 can be fused to a constant domain comprising a YTE or LS mutation as exemplified herein. For example, in some embodiments, the constant domain comprises the amino acid sequence SEQ ID NO: 262 or SEQ ID NO: 261.

[0361] In some embodiments, the antibody comprises the following heavy chain sequence:

[0362] VQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISRSGSTKYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDENYALDWWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ IDNO: 455).

[0363] In some embodiments, the antibody comprises a light chain variable region peptide having one of the following sequences or a variant thereof:

[0364] Table 6:

[0365]

[0366]

[0367]

[0368] In some embodiments, the antibody or antigen-binding fragment thereof comprises a sequence selected from one or more of the following: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:334, SEQ ID NO:335, SEQ ID NO:336, SEQ ID NO:337, SEQ ID NO:338, SEQ ID NO:339, SEQ ID NO:340, SEQ ID NO:341, SEQ ID NO:342, SEQ ID NO:343, SEQ ID NO:344, SEQ ID NO:345, SEQ ID NO:346, SEQ ID NO:347, SEQ IDNO:348, SEQ ID NO:349, SEQ ID NO:350, SEQ ID NO:351, SEQ ID NO:352, SEQ ID NO:353, SEQ ID NO:354, SEQ ID NO:355, SEQ ID NO:356, SEQ ID NO:357, SEQ ID NO:358, SEQ ID NO:359, SEQ ID NO:360, SEQ ID NO:361, SEQ ID NO:362, SEQ ID NO:363, or any variant thereof.

[0369] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 358, 359, 360, 361, 362, or 363 or any variant thereof.

[0370] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 358, 359, 360, 361, 362 or 363.

[0371] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 35358, 359, 360, 361, 362 or 363.

[0372] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide of SEQ ID NO: 1. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 1. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1.

[0373] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide of SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 3.

[0374] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 3.

[0375] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide of SEQ ID NO: 5. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 5. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 5.

[0376] In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH of SEQ ID NO: 7 HPeptide. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85% identity with SEQ ID NO:7. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:7.

[0377] In some embodiments, the antibody or its antigen-binding fragment comprises the VH peptide of SEQ ID NO:9. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85% identity with SEQ ID NO:9. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:9.

[0378] In some embodiments, the antibody or its antigen-binding fragment comprises the VH peptide of SEQ ID NO:11. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85% identity with SEQ ID NO:11. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:11.

[0379] In some embodiments, the antibody or its antigen-binding fragment comprises the VH peptide of SEQ ID NO:13. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85% identity with SEQ ID NO:13. In some embodiments, the antibody or its antigen-binding fragment comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:13.

[0380] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:15. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:15. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:15.

[0381] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:17. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:17. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:17.

[0382] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:19. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:19. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:19.

[0383] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:21. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:21. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:21.

[0384] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:23. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:23. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:23.

[0385] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:25. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:25. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:25.

[0386] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:27. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:27. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:27.

[0387] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:29. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:29. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:29.

[0388] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:31. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO:31. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:31.

[0389] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:33. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO:33. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:33.

[0390] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:35. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO:35. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:35.

[0391] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:37. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO:37. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:37.

[0392] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:39. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:39. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:39.

[0393] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:41. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:41. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:41.

[0394] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:43. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:43. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:43.

[0395] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:45. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:45. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:45.

[0396] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:47. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:47. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:47.

[0397] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:49. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:49. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:49.

[0398] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:51. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:51. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:51.

[0399] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:53. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:53. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:53.

[0400] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:55. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:55. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:55.

[0401] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:57. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:57. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:57.

[0402] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:59. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:59. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:59.

[0403] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:334. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:334. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:334.

[0404] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 335. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 335. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 335.

[0405] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 336. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 336. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 336.

[0406] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 337. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 337. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 337.

[0407] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 338. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 338. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 338.

[0408] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 339. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 339. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 339.

[0409] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 340. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 340. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 340.

[0410] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 341. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 341. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 341.

[0411] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 342. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 342. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 342.

[0412] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 343. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 343. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 343.

[0413] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 344. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 344. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 344.

[0414] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 345. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 345. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 345.

[0415] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 346. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 346. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 346.

[0416] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 347. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO: 347. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 347.

[0417] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 348. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO: 348. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 348.

[0418] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 349. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO: 349. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 349.

[0419] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 350. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity with SEQ ID NO: 350. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 350.

[0420] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 351. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 351. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 351.

[0421] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 352. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 352. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 352.

[0422] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 353. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 353. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 353.

[0423] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 354. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 354. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 354.

[0424] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 355. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 355. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 355.

[0425] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 356. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 356. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 356.

[0426] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 357. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 357. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 357.

[0427] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 358. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 358. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 358.

[0428] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:359. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:359. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:359.

[0429] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:360. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:360. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:360.

[0430] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:361. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:361. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:361.

[0431] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO:362. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO:362. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:362.

[0432] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VH peptide of SEQ ID NO: 363. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85% identity to SEQ ID NO: 363. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 363.

[0433] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, or 60 or any variant thereof. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60. In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60.

[0434] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO: 2. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO: 2. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2.

[0435] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:4. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:4. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:4.

[0436] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:6. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:6. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:6.

[0437] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:8. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:8. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:8.

[0438] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:10. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:10. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:10.

[0439] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:12. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity with SEQ ID NO:12. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:12.

[0440] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:14. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity with SEQ ID NO:14. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:14.

[0441] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:16. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity with SEQ ID NO:16. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:16.

[0442] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:18. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity with SEQ ID NO:18. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO:18.

[0443] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:20. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:20. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:20.

[0444] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:22. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:22. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:22.

[0445] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:24. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:24. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:24.

[0446] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:26. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:26. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:26.

[0447] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:28. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:28. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:28.

[0448] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:30. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:30. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:30.

[0449] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:32. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:32. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:32.

[0450] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:34. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:34. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:34.

[0451] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:36. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:36. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:36.

[0452] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:38. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:38. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:38.

[0453] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:40. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:40. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:40.

[0454] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:42. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:42. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:42.

[0455] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:44. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:44. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:44.

[0456] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:46. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:46. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:46.

[0457] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:48. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:48. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:48.

[0458] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:50. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:50. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:50.

[0459] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:52. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:52. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:52.

[0460] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:54. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:54. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:54.

[0461] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:56. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:56. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:56.

[0462] In some embodiments, the antibody or an antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:58. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:58. In some embodiments, the antibody or an antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:58.

[0463] In some embodiments, the antibody or antigen-binding fragment thereof comprises the VL peptide of SEQ ID NO:60. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85% identity to SEQ ID NO:60. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL peptide having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:60.

[0464] In some embodiments, the antibody or antigen-binding fragment thereof comprises V H peptide and V L peptide, wherein the V H peptide comprises the sequence of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 35358, 359, 360, 361, 362, or 363 or a variant thereof; and the V L peptide comprises the sequence of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, or 60 or a variant thereof. In some embodiments, the antibody or antigen-binding fragment thereof comprises V H peptide and V L peptide, wherein the V H peptide has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 35358, 359, 360, 361, 362 or 363; and the VL The peptide has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60. In some of these embodiments, the V H The peptide comprises the sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 35358, 359, 360, 361, 362 or 363; and the V L The peptide comprises the sequence of SEQID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58 or 60.

[0465] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 1, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 61, SEQ IDNO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 63 or SEQ ID NO: 132, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQID NO: 66.

[0466] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:3, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:67 or SEQ ID NO:135, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:1339, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0467] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:5, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:69 or SEQ ID NO:136, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0468] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:7, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:70 or SEQ ID NO:137, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0469] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:9, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:72 or SEQ ID NO:138, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0470] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:11, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:73 or SEQ ID NO:139, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0471] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:13, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:74 or SEQ ID NO:140, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:75.

[0472] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:15, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:76 or SEQ ID NO:141, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:77.

[0473] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:17, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:78 or SEQ ID NO:142, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:79.

[0474] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 19, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 80 or SEQ ID NO: 143, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 81.

[0475] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 21, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 84 or SEQ ID NO: 146, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 87.

[0476] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 23, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 88 or SEQ ID NO: 149, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0477] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 25, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 90 or SEQ ID NO: 150, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0478] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 27, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 91 or SEQ ID NO: 151, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 92.

[0479] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 29, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 93 or SEQ ID NO: 152, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 94.

[0480] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:31, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:84 or SEQ ID NO:146, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:95.

[0481] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:33, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:96 or SEQ ID NO:153, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:97.

[0482] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 35, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 98 or SEQ ID NO: 154, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 99.

[0483] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 37, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 100 or SEQ ID NO: 155, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 101.

[0484] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:39, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:100 or SEQ ID NO:155, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:102.

[0485] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:41, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:105 or SEQ ID NO:158, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:108.

[0486] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 43, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 109 or SEQ ID NO: 161, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 110.

[0487] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 45, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 111 or SEQ ID NO: 162, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 112.

[0488] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 47, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 105 or SEQ ID NO: 158, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 113.

[0489] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 49, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 114 or SEQ ID NO: 163, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 115.

[0490] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:51, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:116 or SEQ ID NO:164, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:113.

[0491] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:53, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:117 or SEQ ID NO:165, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:118.

[0492] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:55, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:116 or SEQ ID NO:164, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:119.

[0493] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:57, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:120 or SEQ ID NO:166, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:121.

[0494] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:59, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:122 or SEQ ID NO:167, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:123.

[0495] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:334, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:63 or SEQ ID NO:132, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:66.

[0496] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 335, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 67 or SEQ ID NO: 135, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 1339, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 68.

[0497] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 336, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 69 or SEQ ID NO: 136, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 68.

[0498] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 337, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 70 or SEQ ID NO: 137, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 71.

[0499] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 338, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 72 or SEQ ID NO: 138, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 71.

[0500] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 339, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 73 or SEQ ID NO: 139, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 71.

[0501] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 340, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 74 or SEQ ID NO: 140, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 75.

[0502] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 341, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 76 or SEQ ID NO: 141, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 77.

[0503] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 342, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 78 or SEQ ID NO: 142, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 79.

[0504] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 343, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 61, SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 80 or SEQ ID NO: 143, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 81.

[0505] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 344, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 84 or SEQ ID NO: 146, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 87.

[0506] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 345, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 88 or SEQ ID NO: 149, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0507] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 346, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 90 or SEQ ID NO: 150, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0508] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 347, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 91 or SEQ ID NO: 151, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 92.

[0509] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 348, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 93 or SEQ ID NO: 152, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 94.

[0510] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 349, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 84 or SEQ ID NO: 146, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 95.

[0511] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 350, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 96 or SEQ ID NO: 153, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 97.

[0512] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 351, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 98 or SEQ ID NO: 154, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 99.

[0513] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 352, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 100 or SEQ ID NO: 155, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 101.

[0514] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 353, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 100 or SEQ ID NO: 155, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 102.

[0515] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 354, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 105 or SEQ ID NO: 158, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 108.

[0516] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 355, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 109 or SEQ ID NO: 161, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 110.

[0517] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 356, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 111 or SEQ ID NO: 162, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 112.

[0518] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 357, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 105 or SEQ ID NO: 158, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 113.

[0519] In some embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 358, wherein the antibody or its antigen-binding fragment retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 114 or SEQ ID NO: 163, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 115.

[0520] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 359, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 116 or SEQ ID NO: 164, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 113.

[0521] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 360, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 117 or SEQ ID NO: 165, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 118.

[0522] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 361, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 116 or SEQ ID NO: 164, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 119.

[0523] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 362, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 120 or SEQ ID NO: 166, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 121.

[0524] In some embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 363, wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 122 or SEQ ID NO: 167, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 123.

[0525] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 2, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence 61 of SEQ ID NO: 2, the HCDR1 sequence of SEQ ID NO: 124 or SEQ ID NO: 130, retains the HCDR2 sequence of SEQ ID NO: 62, SEQ ID NO: 125 or SEQ ID NO: 131, retains the HCDR3 sequence of SEQ ID NO: 63 or SEQ ID NO: 132, retains the LCDR1 sequence of SEQ ID NO: 64 or SEQ ID NO: 133, retains the LCDR2 sequence of SEQ ID NO: 65 or SEQ ID NO: 134, and retains the LCDR3 sequence of SEQ ID NO: 66.

[0526] In some embodiments, the light chain of the antibody or its antigen-binding fragment comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:4, wherein the antibody or its antigen-binding fragment maintains the HCDR1 sequence of SEQ ID NO:61, the HCDR1 sequence of SEQ ID NO:124 or the HCDR1 sequence of SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, the HCDR2 sequence of SEQ ID NO:125 or the HCDR2 sequence of SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:67 or the HCDR3 sequence of SEQ ID NO:135, retains the LCDR1 sequence of SEQ ID NO:64 or the LCDR1 sequence of SEQ ID NO:1339, retains the LCDR2 sequence of SEQ ID NO:65 or the LCDR2 sequence of SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0527] In some embodiments, the light chain of the antibody or its antigen-binding fragment comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:6 and having HCDR1, wherein the antibody or its antigen-binding fragment maintains the HCDR1 sequence of SEQ ID NO:61, the HCDR1 sequence of SEQ ID NO:124 or the HCDR1 sequence of SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, the HCDR2 sequence of SEQ ID NO:125 or the HCDR2 sequence of SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:69 or the HCDR3 sequence of SEQ ID NO:136, retains the LCDR1 sequence of SEQ ID NO:64 or the LCDR1 sequence of SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or the LCDR2 sequence of SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0528] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:8 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:70 or SEQ ID NO:137, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0529] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:10 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:72 or SEQ ID NO:138, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0530] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:12 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:73 or SEQ ID NO:139, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0531] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:14 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:74 or SEQ ID NO:140, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:75.

[0532] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:16 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:76 or SEQ ID NO:141, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:77.

[0533] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:18 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:78 or SEQ ID NO:142, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:79.

[0534] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:20 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:80 or SEQ ID NO:143, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:81.

[0535] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:22 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:84 or SEQ ID NO:146, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:87.

[0536] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 24 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 88 or SEQ ID NO: 149, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0537] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 26 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 90 or SEQ ID NO: 150, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0538] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:28 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:91 or SEQ ID NO:151, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:92.

[0539] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:30 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:93 or SEQ ID NO:152, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:94.

[0540] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 32 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 84 or SEQ ID NO: 146, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 95.

[0541] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 34 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 96 or SEQ ID NO: 153, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 97.

[0542] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:36 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:98 or SEQ ID NO:154, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:99.

[0543] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:38 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:100 or SEQ ID NO:155, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:101.

[0544] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:40 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:100 or SEQ ID NO:155, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:102.

[0545] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:42 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:105 or SEQ ID NO:158, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:108.

[0546] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 44 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 109 or SEQ ID NO: 161, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 110.

[0547] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 46 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156, retains the HCDR2 sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157, retains the HCDR3 sequence of SEQ ID NO: 111 or SEQ ID NO: 162, retains the LCDR1 sequence of SEQ ID NO: 106 or SEQ ID NO: 159, retains the LCDR2 sequence of SEQ ID NO: 107 or SEQ ID NO: 160, and retains the LCDR3 sequence of SEQ ID NO: 112.

[0548] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:48 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:105 or SEQ ID NO:158, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:113.

[0549] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:50 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:114 or SEQ ID NO:163, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:115.

[0550] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:52 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:116 or SEQ ID NO:164, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:113.

[0551] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:54 HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:117 or SEQ ID NO:165, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:118.

[0552] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:56 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:116 or SEQ ID NO:164, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:119.

[0553] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:58 in HCDR1, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:120 or SEQ ID NO:166, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:121.

[0554] In some embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain variable region having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:60, wherein the antibody or antigen-binding fragment thereof maintains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:122 or SEQ ID NO:167, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:123.

[0555] The V H and V L sequences can be in any form, including but not limited to the scFv format, wherein the V H and V L regions are linked by a peptide linker. Examples of peptide linkers that can be used to link the various peptides provided herein include but are not limited to: (GGGGS) n (SEQ ID NO:266); (GGGGA) n (SEQ ID NO:267), or any combination thereof, wherein each n is independently 1-5. In some embodiments, each n is independently 1. In some embodiments, each n is independently 2. In some embodiments, each n is independently 3. In some embodiments, each n is independently 4. In some embodiments, each n is independently 5. In some embodiments, the variable regions are not linked by a peptide linker.

[0556] In some embodiments, the antibody comprises SEQ ID NO:1 and SEQ ID NO:2. In some embodiments, the antibody comprises SEQ ID NO:3 and SEQ ID NO:4. In some embodiments, the antibody comprises SEQ ID NO:5 and SEQ ID NO:6. In some embodiments, the antibody comprises SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the antibody comprises SEQ ID NO:9 and SEQ ID NO:10. In some embodiments, the antibody comprises SEQ ID NO:11 and SEQ ID NO:12. In some embodiments, the antibody comprises SEQ ID NO:13 and SEQ ID NO:14. In some embodiments, the antibody comprises SEQ ID NO:15 and SEQ ID NO:16. In some embodiments, the antibody comprises SEQ ID NO:17 and SEQ ID NO:18. In some embodiments, the antibody comprises SEQ ID NO:19 and SEQ ID NO:20. In some embodiments, the antibody comprises SEQ ID NO:21 and SEQ ID NO:22. In some embodiments, the antibody comprises SEQ ID NO:23 and SEQ ID NO:24. In some embodiments, the antibody comprises SEQ ID NO:25 and SEQ ID NO:26. In some embodiments, the antibody comprises SEQ ID NO:27 and SEQ ID NO:28. In some embodiments, the antibody comprises SEQ ID NO:29 and SEQ ID NO:30. In some embodiments, the antibody comprises SEQ ID NO:31 and SEQ ID NO:32. In some embodiments, the antibody comprises SEQ ID NO:33 and SEQ ID NO:34. In some embodiments, the antibody comprises SEQ ID NO:35 and SEQ ID NO:36. In some embodiments, the antibody comprises SEQ ID NO:37 and SEQ ID NO:38. In some embodiments, the antibody comprises SEQ ID NO:39 and SEQ ID NO:40. In some embodiments, the antibody comprises SEQ ID NO:41 and SEQ ID NO:42. In some embodiments, the antibody comprises SEQ ID NO:43 and SEQ ID NO:44. In some embodiments, the antibody comprises SEQ ID NO:45 and SEQ ID NO:46. In some embodiments, the antibody comprises SEQ ID NO:47 and SEQ ID NO:48. In some embodiments, the antibody comprises SEQ ID NO:49 and SEQ ID NO:50. In some embodiments, the antibody comprises SEQ ID NO:51 and SEQ ID NO:52.In some embodiments, the antibody comprises SEQ ID NO:53 and SEQ ID NO:54. In some embodiments, the antibody comprises SEQ ID NO:55 and SEQ ID NO:56. In some embodiments, the antibody comprises SEQ ID NO:57 and SEQ ID NO:58. In some embodiments, the antibody comprises SEQ ID NO:59 and SEQ ID NO:60. In some embodiments, the antibody comprises SEQ ID NO:334 and SEQ ID NO:2. In some embodiments, the antibody comprises SEQ ID NO:335 and SEQ ID NO:4. In some embodiments, the antibody comprises SEQ ID NO:336 and SEQ ID NO:6. In some embodiments, the antibody comprises SEQ ID NO:337 and SEQ ID NO:8. In some embodiments, the antibody comprises SEQ ID NO:338 and SEQ ID NO:10. In some embodiments, the antibody comprises SEQ ID NO:339 and SEQ ID NO:12. In some embodiments, the antibody comprises SEQ ID NO:340 and SEQ ID NO:14. In some embodiments, the antibody comprises SEQ ID NO:341 and SEQ ID NO:16. In some embodiments, the antibody comprises SEQ ID NO:342 and SEQ ID NO:18. In some embodiments, the antibody comprises SEQ ID NO:343 and SEQ ID NO:20. In some embodiments, the antibody comprises SEQ ID NO:344 and SEQ ID NO:22. In some embodiments, the antibody comprises SEQ ID NO:345 and SEQ ID NO:24. In some embodiments, the antibody comprises SEQ ID NO:346 and SEQ ID NO:26. In some embodiments, the antibody comprises SEQ ID NO:347 and SEQ ID NO:28. In some embodiments, the antibody comprises SEQ ID NO:348 and SEQ ID NO:30. In some embodiments, the antibody comprises SEQ ID NO:349 and SEQ ID NO:32. In some embodiments, the antibody comprises SEQ ID NO:350 and SEQ ID NO:34. In some embodiments, the antibody comprises SEQ ID NO:351 and SEQ ID NO:36. In some embodiments, the antibody comprises SEQ ID NO:352 and SEQ ID NO:38. In some embodiments, the antibody comprises SEQ ID NO:353 and SEQ ID NO:40. In some embodiments, the antibody comprises SEQ ID NO:354 and SEQ ID NO:42.In some embodiments, the antibody comprises SEQ ID NO:355 and SEQ ID NO:44. In some embodiments, the antibody comprises SEQ ID NO:356 and SEQ ID NO:46. In some embodiments, the antibody comprises SEQ ID NO:357 and SEQ ID NO:48. In some embodiments, the antibody comprises SEQ ID NO:358 and SEQ ID NO:50. In some embodiments, the antibody comprises SEQ ID NO:359 and SEQ ID NO:52. In some embodiments, the antibody comprises SEQ ID NO:360 and SEQ ID NO:54. In some embodiments, the antibody comprises SEQ ID NO:361 and SEQ ID NO:56. In some embodiments, the antibody comprises SEQ ID NO:362 and SEQ ID NO:58. In some embodiments, the antibody comprises SEQ ID NO:363 and SEQ ID NO:60.

[0557] As provided herein, the different peptides (V H or V L ) described herein may be linked to a peptide linker or, instead of being linked to a peptide linker, form a continuous sequence. In some embodiments, the heavy chain variable region and the light chain variable region are not linked by a linker. In some embodiments, the heavy chain variable region and the light chain variable region are linked via a peptide linker. In some embodiments, the peptide linker comprises (GGGGS) n (SEQ ID NO:266); (GGGGA) n (SEQ ID NO:267) or a sequence of any combination thereof, where each n is independently 1-5. In some embodiments, each n is independently 1. In some embodiments, each n is independently 2. In some embodiments, each n is independently 3. In some embodiments, each n is independently 4. In some embodiments, each n is independently 5. The linked peptide format may be represented by the formula V H -Z-V L or V L -Z-V H , where Z is the peptide linker. In some embodiments, Z is (GGGGS) n (SEQ ID NO:266); (GGGGA) n (SEQ ID NO:267) or any combination thereof, where each n is independently 1-5. In some embodiments, each n is independently 1. In some embodiments, each n is independently 2. In some embodiments, each n is independently 3. In some embodiments, each n is independently 4. In some embodiments, each n is independently 5.

[0558] In some embodiments, the VH and VL polypeptides are linked to an Fc region, such as "IgG4 S228P L235E LS" or "IgG4 S228P L235E YTE". In some embodiments, the Fc region is as provided herein. In some embodiments, the Fc region is "IgG4 S228P L235E LS". In some embodiments, the Fc region is "IgG4 S228 L235E YTE".

[0559] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H peptide and a V L peptide. In some embodiments, each of VH and VL independently comprises 1, 2, 3, 4, or 5 conservative amino acid substitutions. In some embodiments, the CDRs of VH and VL comprise no more than 1 conservative amino acid substitution. Thus, in some embodiments, HCDR1, HCDR2, or HCDR3 may comprise one or no conservative amino acid substitutions. Additionally, in some embodiments, LCDR1, LCDR2, or LCDR3 may comprise one or no conservative amino acid substitutions.

[0560] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO:2, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO:1, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:63 or SEQ ID NO:132, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:66.

[0561] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:4, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:3, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:67 or SEQ ID NO:135, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:1339, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0562] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:6, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:5, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:69 or SEQ ID NO:136, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:68.

[0563] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:8, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:7, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:70 or SEQ ID NO:137, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0564] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:10, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:9, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:72 or SEQ ID NO:138, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0565] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:12, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:11, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:73 or SEQ ID NO:139, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:71.

[0566] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:14, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:13, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:74 or SEQ ID NO:140, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:75.

[0567] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:16, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:15, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:76 or SEQ ID NO:141, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:77.

[0568] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:18, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:17, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:78 or SEQ ID NO:142, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:79.

[0569] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:20, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:19, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:61, SEQ ID NO:124 or SEQ ID NO:130, retains the HCDR2 sequence of SEQ ID NO:62, SEQ ID NO:125 or SEQ ID NO:131, retains the HCDR3 sequence of SEQ ID NO:80 or SEQ ID NO:143, retains the LCDR1 sequence of SEQ ID NO:64 or SEQ ID NO:133, retains the LCDR2 sequence of SEQ ID NO:65 or SEQ ID NO:134, and retains the LCDR3 sequence of SEQ ID NO:81.

[0570] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:22, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:21, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:84 or SEQ ID NO:146, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:87.

[0571] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 24, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 23, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 88 or SEQ ID NO: 149, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 89.

[0572] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:26, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:25, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:90 or SEQ ID NO:150, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:89.

[0573] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:28, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:27, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:91 or SEQ ID NO:151, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:92.

[0574] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:30, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:29, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:93 or SEQ ID NO:152, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:94.

[0575] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:32, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:31, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:84 or SEQ ID NO:146, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:95.

[0576] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 34, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 33, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 96 or SEQ ID NO: 153, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 97.

[0577] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 36, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 35, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO: 82, SEQ ID NO: 126 or SEQ ID NO: 144, retains the HCDR2 sequence of SEQ ID NO: 83, SEQ ID NO: 127 or SEQ ID NO: 145, retains the HCDR3 sequence of SEQ ID NO: 98 or SEQ ID NO: 154, retains the LCDR1 sequence of SEQ ID NO: 85 or SEQ ID NO: 147, retains the LCDR2 sequence of SEQ ID NO: 86 or SEQ ID NO: 148, and retains the LCDR3 sequence of SEQ ID NO: 99.

[0578] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:38, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:37, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:100 or SEQ ID NO:155, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:101.

[0579] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:40, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:39, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144, retains the HCDR2 sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145, retains the HCDR3 sequence of SEQ ID NO:100 or SEQ ID NO:155, retains the LCDR1 sequence of SEQ ID NO:85 or SEQ ID NO:147, retains the LCDR2 sequence of SEQ ID NO:86 or SEQ ID NO:148, and retains the LCDR3 sequence of SEQ ID NO:102.

[0580] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:44, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:41, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:105 or SEQ ID NO:158, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:108.

[0581] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:44, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:43, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:109 or SEQ ID NO:161, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:110.

[0582] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:46, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:45, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:111 or SEQ ID NO:162, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:112.

[0583] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:48, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:47, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:105 or SEQ ID NO:158, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:113.

[0584] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:50, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO:49, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:114 or SEQ ID NO:163, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:115.

[0585] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO:52, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO:51, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:116 or SEQ ID NO:164, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:113.

[0586] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO:54, the heavy chain variable region of the heavy chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO:55, and wherein the antibody or antigen-binding fragment thereof retains the HCDR1 sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156, retains the HCDR2 sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157, retains the HCDR3 sequence of SEQ ID NO:117 or SEQ ID NO:165, retains the LCDR1 sequence of SEQ ID NO:106 or SEQ ID NO:159, retains the LCDR2 sequence of SEQ ID NO:107 or SEQ ID NO:160, and retains the LCDR3 sequence of SEQ ID NO:118.

[0587] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the light chain has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%...

Claims

1. An antibody or antigen-binding fragment thereof, wherein the antibody or antibody fragment comprises: A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 has the amino acid sequence of SEQ ID NO: 61, the HCDR2 has the amino acid sequence of SEQ ID NO: 62, and the HCDR3 has the amino acid sequence of SEQ ID NO: 78; and A light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 has the amino acid sequence of SEQ ID NO: 64, the LCDR2 has the amino acid sequence of SEQ ID NO: 65, and the LCDR3 has the amino acid sequence of SEQ ID NO:

79.

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

342.

3. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

342.

4. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:

342.

5. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

17.

6. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

17.

7. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:

17.

8. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

454.

9. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

454.

10. The antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:

454.

11. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain that is at least 90% identical to the amino acid sequence of SEQ ID NO:

381.

12. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain that is at least 95% identical to the amino acid sequence of SEQ ID NO:

381.

13. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:

381.

14. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

185.

15. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:

185.

16. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:

185.

17. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the light chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

18.

18. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the light chain variable region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:

18.

19. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:

18.

20. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the antibody comprises a light chain that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

236.

21. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the antibody comprises a light chain that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:

236.

22. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 16, wherein the antibody comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:

236.

23. The antibody according to claim 1, wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain region having the amino acid sequence set forth in SEQ ID NO: 342 and a light chain variable region having the sequence set forth in SEQ ID NO:

18.

24. The antibody according to claim 23, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain having the sequence set forth in SEQ ID NO: 381 and a light chain having the sequence set forth in SEQ ID NO:

236.

25. The antibody according to claim 1, wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain region having the amino acid sequence set forth in SEQ ID NO: 17 and a light chain variable region having the sequence set forth in SEQ ID NO18.

26. The antibody according to claim 23, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain having the sequence set forth in SEQ ID NO: 185 and a light chain having the sequence set forth in SEQ ID NO:

236.

27. An antibody or antigen-binding fragment thereof, wherein the antibody or antibody fragment comprises: (a) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has an amino acid sequence selected from SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has an amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131, and the heavy chain HCDR3 sequence has an amino acid sequence of SEQ ID NO:63 or SEQ ID NO:132, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has an amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has an amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has an amino acid sequence of SEQ ID NO:66; or a variant or conventional equivalent of any of the foregoing; (b) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has an amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has an amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has an amino acid sequence of SEQ ID NO:67 or SEQ ID NO:135, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has an amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has an amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has an amino acid sequence of SEQ ID NO:68; or a variant or conventional equivalent of any of the foregoing; (c) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:69 or SEQ ID NO:136, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:68; or a variant or conventional equivalent of any of the foregoing; (d) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:70 or SEQ ID NO:137, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:71; or a variant or conventional equivalent of any of the foregoing; (e) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:72 or SEQ ID NO:138, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:71; or a variant or conventional equivalent of any of the foregoing; (f) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:73 or SEQ ID NO:139, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:71; or a variant or conventional equivalent of any of the foregoing; (g) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:74 or SEQ ID NO:140, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:75; or a variant or conventional equivalent of any of the foregoing; (h) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:76 or SEQ ID NO:141, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:77; or a variant or conventional equivalent of any of the foregoing; (i) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:78 or SEQ ID NO:142, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:79; or a variant or conventional equivalent of any of the foregoing; (j) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:61, SEQ ID NO:124, or SEQ ID NO:130; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:62, SEQ ID NO:125, or SEQ ID NO:131; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:80 or SEQ ID NO:143, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:64 or SEQ ID NO:133; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:65 or SEQ ID NO:134; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:81; or a variant or conventional equivalent of any of the foregoing; (k) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:84 or SEQ ID NO:146, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:87; or a variant or conventional equivalent of any of the foregoing; (l) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:88 or SEQ ID NO:149, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:89; or a variant or conventional equivalent of any of the foregoing; (m) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:90 or SEQ ID NO:150, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:89; or a variant or conventional equivalent of any of the foregoing; (n) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:91 or SEQ ID NO:151, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:92; or a variant or conventional equivalent of any of the foregoing; (o) A heavy chain variable region, which comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:93 or SEQ ID NO:152, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region, which comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:94; or a variant or conventional equivalent of any of the foregoing; (p) A heavy chain variable region, which comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:84 or SEQ ID NO:146, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region, which comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:95; or a variant or conventional equivalent of any of the foregoing; (q) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:96 or SEQ ID NO:153, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:97; or a variant or conventional equivalent of any of the foregoing; (r) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126, or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127, or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:98 or SEQ ID NO:154, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:99; or a variant or conventional equivalent of any of the foregoing; (s) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:100 or SEQ ID NO:155, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:101; or a variant or conventional equivalent of any of the foregoing; (t) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:82, SEQ ID NO:126 or SEQ ID NO:144; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:83, SEQ ID NO:127 or SEQ ID NO:145; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:100 or SEQ ID NO:155, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:85 or SEQ ID NO:147; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:86 or SEQ ID NO:148; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:102; or a variant or conventional equivalent of any of the foregoing; (u) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:105 or SEQ ID NO:158, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:106 or SEQ ID NO:159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:107 or SEQ ID NO:160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:108; or a variant or conventional equivalent of any of the foregoing; (v) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO:103, SEQ ID NO:128 or SEQ ID NO:156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO:104, SEQ ID NO:129 or SEQ ID NO:157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO:109 or SEQ ID NO:161, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO:106 or SEQ ID NO:159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO:107 or SEQ ID NO:160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO:110; or a variant or conventional equivalent of any of the foregoing; (w) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128, or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129, or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 111 or SEQ ID NO: 162, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 112; or a variant or conventional equivalent of any of the foregoing; (x) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128, or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129, or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 105 or SEQ ID NO: 158, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 113; or a variant or conventional equivalent of any of the foregoing; (y) The heavy chain variable region, which comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 114 or SEQ ID NO: 163, or a variant or conventional equivalent of any of the foregoing; and (ii) the light chain variable region, which comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 115; or a variant or conventional equivalent of any of the foregoing; (z) The heavy chain variable region, which comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 164, or a variant or conventional equivalent of any of the foregoing; and (ii) the light chain variable region, which comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 113; or a variant or conventional equivalent of any of the foregoing; (aa) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 117 or SEQ ID NO: 165, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 118; or a variant or conventional equivalent of any of the foregoing; (ab) A heavy chain variable region comprising heavy chain HCDR1, HCDR2 and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128 or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129 or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 164, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2 and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 119; or a variant or conventional equivalent of any of the foregoing; (ac) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128, or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129, or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 166, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 121; or a variant or conventional equivalent of any of the foregoing; (ad) A heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 128, or SEQ ID NO: 156; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 104, SEQ ID NO: 129, or SEQ ID NO: 157; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 167, or a variant or conventional equivalent of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence of SEQ ID NO: 106 or SEQ ID NO: 159; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 160; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 123; or a variant or conventional equivalent of any of the foregoing.

28. The antibody or antigen-binding fragment thereof according to claim 26, wherein the antibody or antigen-binding fragment thereof comprises: (a) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:2, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:1, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection a of claim 1; or (b) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:4, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:3, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection b of claim 1; or (c) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:6, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:5, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection c of claim 1; or (d) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:8, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:7, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection d of claim 1; or (e) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:10, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:9, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection e of claim 1; or (f) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:12, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:11, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection f of claim 1; or (g) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:14, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:13, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection g of claim 1; or (h) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:16, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:15, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection h of claim 1; or (i) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:18, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:17, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection i of claim 1; or (j) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:20, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:19, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection j of claim 1; or (k) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:22, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:21, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection k of claim 1; or (l) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:24, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:23, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection l of claim 1; or (m) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 26, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 25, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart m of claim 1; or (n) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 28, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 27, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart n of claim 1; or (o) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 30, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 29, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart o of claim 1; or (p) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 32, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 31, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart p of claim 1; or (q) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 34, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 33, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart q of claim 1; or (r) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 36, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 35, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart r of claim 1; or (s) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 38, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 37, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part s of claim 1; or (t) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 40, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 39, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part t of claim 1; or (u) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 42, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 41, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part u of claim 1; or (v) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 44, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 43, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part v of claim 1; or (w) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 46, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 45, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part w of claim 1; or (x) the light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO: 48, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO: 47, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in sub-part x of claim 1; or (y) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:50, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:49, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart y of claim 1; or (z) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:52, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:51, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart z of claim 1; or (aa) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:54, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:53, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart ab of claim 1; or (ab) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 56, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 55, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart ac of claim 1; or (ac) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:58, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:57, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart ad of claim 1; or (ad) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:60, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:59, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart ae of claim 1; or (ae) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:2, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:334, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart a of claim 1; or (af) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 4, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 335, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part b of claim 1; or (ag) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 6, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 336, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part c of claim 1; or (ah) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 8, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 337, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part d of claim 1; or (ai) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 10, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 338, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part e of claim 1; or (aj) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 12, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 339, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part f of claim 1; or (ak) The light-chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 14, and the heavy-chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 340, wherein the antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part g of claim 1; or (al) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 16, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 341, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart h of claim 1; or (am) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 18, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 342, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart i of claim 1; or (an) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 20, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 343, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart j of claim 1; or (ao) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 22, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 344, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart k of claim 1; or (ap) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 24, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 345, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart l of claim 1; or (aq) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 26, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 346, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subpart m of claim 1; or (ar)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:28, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:347, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection n of claim 1; or (as)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:30, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:348, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection o of claim 1; or (at)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:32, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:349, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection p of claim 1; or (au)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:34, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:350, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection q of claim 1; or (av)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:36, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:351, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection r of claim 1; or (aw)The light chain variable region of said light chain, which has at least 90% sequence identity with SEQ ID NO:38, and the heavy chain variable region of said heavy chain, which has at least 90% sequence identity with SEQ ID NO:352, wherein said antibody or antigen-binding fragment thereof retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in subsection s of claim 1; or (ax) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 40, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 353, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part t of claim 1; or (ay) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 42, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 354, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part u of claim 1; or (az) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 44, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 355, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part v of claim 1; or (ba) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 46, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 356, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part w of claim 1; or (bb) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 48, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 357, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part x of claim 1; or (bc) The light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO: 50, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO: 358, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences shown in sub-part y of claim 1; or (bd) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:52, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:359, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart z of claim 1; or (be) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:54, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:360, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart ab of claim 1; or (bf) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:56, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:361, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart ac of claim 1; or (bg) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:58, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:362, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart ad of claim 1; or (bh) the light chain variable region of the light chain, which has at least 90% sequence identity with SEQ ID NO:60, and the heavy chain variable region of the heavy chain, which has at least 90% sequence identity with SEQ ID NO:363, wherein the antibody or its antigen-binding fragment retains the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences shown in subpart ae of claim 1.

29. The antibody or its antigen-binding fragment according to claim 28, wherein: (a) the light chain variable region comprises SEQ ID NO:2, and the heavy chain variable region comprises SEQ ID NO:1; (b) the light chain variable region comprises SEQ ID NO:4, and the heavy chain variable region comprises SEQ ID NO:3; (c) the light chain variable region comprises SEQ ID NO:6, and the heavy chain variable region comprises SEQ ID NO:5; (d) the light chain variable region comprises SEQ ID NO:8, and the heavy chain variable region comprises SEQ ID NO:7; (e) The light chain variable region comprises SEQ ID NO:10, and the heavy chain variable region comprises SEQ ID NO:9; (f) The light chain variable region comprises SEQ ID NO:12, and the heavy chain variable region comprises SEQ ID NO:11; (g) The light chain variable region comprises SEQ ID NO:14, and the heavy chain variable region comprises SEQ ID NO:13; (h) The light chain variable region comprises SEQ ID NO:16, and the heavy chain variable region comprises SEQ ID NO:15; (i) The light chain variable region comprises SEQ ID NO:18, and the heavy chain variable region comprises SEQ ID NO:17; (j) The light chain variable region comprises SEQ ID NO:20, and the heavy chain variable region comprises SEQ ID NO:19; (k) The light chain variable region comprises SEQ ID NO:22, and the heavy chain variable region comprises SEQ ID NO:21; (l) The light chain variable region comprises SEQ ID NO:24, and the heavy chain variable region comprises SEQ ID NO:23; (m) The light chain variable region comprises SEQ ID NO:26, and the heavy chain variable region comprises SEQ ID NO:25; (n) The light chain variable region comprises SEQ ID NO:28, and the heavy chain variable region comprises SEQ ID NO:27; (o) The light chain variable region comprises SEQ ID NO:30, and the heavy chain variable region comprises SEQ ID NO:29; (p) The light chain variable region comprises SEQ ID NO:32, and the heavy chain variable region comprises SEQ ID NO:31; (q) The light chain variable region comprises SEQ ID NO:34, and the heavy chain variable region comprises SEQ ID NO:33; (r) The light chain variable region comprises SEQ ID NO:36, and the heavy chain variable region comprises SEQ ID NO:35; (s) The light chain variable region comprises SEQ ID NO:38, and the heavy chain variable region comprises SEQ ID NO:37; (t) The light chain variable region comprises SEQ ID NO:40, and the heavy chain variable region comprises SEQ ID NO:39; (u) The light chain variable region comprises SEQ ID NO:42, and the heavy chain variable region comprises SEQ ID NO:41; (v) The light chain variable region comprises SEQ ID NO:44, and the heavy chain variable region comprises SEQ ID NO:43; (w) The light chain variable region comprises SEQ ID NO:46, and the heavy chain variable region comprises SEQ ID NO:45; (x) The light chain variable region comprises SEQ ID NO:48, and the heavy chain variable region comprises SEQ ID NO:47; (y) The light chain variable region comprises SEQ ID NO:50, and the heavy chain variable region comprises SEQ ID NO:49; (z) The light chain variable region comprises SEQ ID NO:52, and the heavy chain variable region comprises SEQ ID NO:51; (aa) The light chain variable region comprises SEQ ID NO:54, and the heavy chain variable region comprises SEQ ID NO:53; (ab) The light chain variable region comprises SEQ ID NO:56, and the heavy chain variable region comprises SEQ ID NO:55; (ac) The light chain variable region comprises SEQ ID NO:58, and the heavy chain variable region comprises SEQ ID NO:57; (ad) The light chain variable region comprises SEQ ID NO:60, and the heavy chain variable region comprises SEQ ID NO:59; or (ae) The light chain variable region comprises SEQ ID NO:2, and the heavy chain variable region comprises SEQ ID NO:334; (af) The light chain variable region comprises SEQ ID NO:4, and the heavy chain variable region comprises SEQ ID NO:335; (ag) The light chain variable region comprises SEQ ID NO:6, and the heavy chain variable region comprises SEQ ID NO:336; (ah) The light chain variable region comprises SEQ ID NO:8, and the heavy chain variable region comprises SEQ ID NO:337; (ai) The light chain variable region comprises SEQ ID NO:10, and the heavy chain variable region comprises SEQ ID NO:338; (aj) The light chain variable region comprises SEQ ID NO:12, and the heavy chain variable region comprises SEQ ID NO:339; (ak) The light chain variable region comprises SEQ ID NO:14, and the heavy chain variable region comprises SEQ ID NO:340; (al) The light chain variable region comprises SEQ ID NO:16, and the heavy chain variable region comprises SEQ ID NO:341; (am) The light chain variable region comprises SEQ ID NO:18, and the heavy chain variable region comprises SEQ ID NO:342; (an) The light chain variable region comprises SEQ ID NO:20, and the heavy chain variable region comprises SEQ ID NO:343; (ao) The light chain variable region comprises SEQ ID NO:22, and the heavy chain variable region comprises SEQ ID NO:344; (ap) The light chain variable region comprises SEQ ID NO:24, and the heavy chain variable region comprises SEQ ID NO:345; (aq) The light chain variable region comprises SEQ ID NO:26, and the heavy chain variable region comprises SEQ ID NO:346; (ar)The light chain variable region comprises SEQ ID NO:28, and the heavy chain variable region comprises SEQ ID NO:347; (as)The light chain variable region comprises SEQ ID NO:30, and the heavy chain variable region comprises SEQ ID NO:348; (at)The light chain variable region comprises SEQ ID NO:32, and the heavy chain variable region comprises SEQ ID NO:349; (au)The light chain variable region comprises SEQ ID NO:34, and the heavy chain variable region comprises SEQ ID NO:350; (av)The light chain variable region comprises SEQ ID NO:36, and the heavy chain variable region comprises SEQ ID NO:351; (aw)The light chain variable region comprises SEQ ID NO:38, and the heavy chain variable region comprises SEQ ID NO:352; (ax)The light chain variable region comprises SEQ ID NO:40, and the heavy chain variable region comprises SEQ ID NO:353; (ay)The light chain variable region comprises SEQ ID NO:42, and the heavy chain variable region comprises SEQ ID NO:354; (az)The light chain variable region comprises SEQ ID NO:44, and the heavy chain variable region comprises SEQ ID NO:355; (ba)The light chain variable region comprises SEQ ID NO:46, and the heavy chain variable region comprises SEQ ID NO:356; (bb)The light chain variable region comprises SEQ ID NO:48, and the heavy chain variable region comprises SEQ ID NO:357; (bc)The light chain variable region comprises SEQ ID NO:50, and the heavy chain variable region comprises SEQ ID NO:358; (bd)The light chain variable region comprises SEQ ID NO:52, and the heavy chain variable region comprises SEQ ID NO:359; (be)The light chain variable region comprises SEQ ID NO:54, and the heavy chain variable region comprises SEQ ID NO:360; (bf)The light chain variable region comprises SEQ ID NO:56, and the heavy chain variable region comprises SEQ ID NO:361; (bg)The light chain variable region comprises SEQ ID NO:58, and the heavy chain variable region comprises SEQ ID NO:362; or (bh)The light chain variable region comprises SEQ ID NO:60, and the heavy chain variable region comprises SEQ ID NO:

363.

30. The antibody or antigen-binding fragment thereof according to claim 29, wherein: (a) The light chain comprises SEQ ID NO:228, and the heavy chain comprises SEQ ID NO:168 or SEQ ID NO:169; or (b) The light chain comprises SEQ ID NO:229, and the heavy chain comprises SEQ ID NO:170 or SEQ ID NO:171; or (c) The light chain comprises SEQ ID NO:230, and the heavy chain comprises SEQ ID NO:172 or SEQ ID NO:173; or (d) The light chain comprises SEQ ID NO:231, and the heavy chain comprises SEQ ID NO:174 or SEQ ID NO:175; or (e) The light chain comprises SEQ ID NO:232, and the heavy chain comprises SEQ ID NO:176 or SEQ ID NO:177; or (f) The light chain comprises SEQ ID NO:233, and the heavy chain comprises SEQ ID NO:178 or SEQ ID NO:179; or (g) The light chain comprises SEQ ID NO:234, and the heavy chain comprises SEQ ID NO:180 or SEQ ID NO:181; or (h) The light chain comprises SEQ ID NO:235, and the heavy chain comprises SEQ ID NO:182 or SEQ ID NO:183; or (i) The light chain comprises SEQ ID NO:236, and the heavy chain comprises SEQ ID NO:184 or SEQ ID NO:185; or (j) The light chain comprises SEQ ID NO:237, and the heavy chain comprises SEQ ID NO:186 or SEQ ID NO:187; or (k) The light chain comprises SEQ ID NO:238, and the heavy chain comprises SEQ ID NO:188 or SEQ ID NO:189; or (l) The light chain comprises SEQ ID NO:239, and the heavy chain comprises SEQ ID NO:190 or SEQ ID NO:191; or (m) The light chain comprises SEQ ID NO:240, and the heavy chain comprises SEQ ID NO:192 or SEQ ID NO:193; or (n) The light chain comprises SEQ ID NO:241, and the heavy chain comprises SEQ ID NO:194 or SEQ ID NO:195; or (o) The light chain comprises SEQ ID NO:242, and the heavy chain comprises SEQ ID NO:196 or SEQ ID NO:197; or (p) The light chain comprises SEQ ID NO:243, and the heavy chain comprises SEQ ID NO:198 or SEQ ID NO:199; or (q) The light chain comprises SEQ ID NO:244, and the heavy chain comprises SEQ ID NO:200 or SEQ ID NO:201; or (r) The light chain comprises SEQ ID NO:245, and the heavy chain comprises SEQ ID NO:202 or SEQ ID NO:203; or (s) The light chain comprises SEQ ID NO:246, and the heavy chain comprises SEQ ID NO:204 or SEQ ID NO:205; or (t) The light chain comprises SEQ ID NO:247, and the heavy chain comprises SEQ ID NO:206 or SEQ ID NO:207; or (u) The light chain comprises SEQ ID NO:248, and the heavy chain comprises SEQ ID NO:208 or SEQ ID NO:209; or (v) The light chain comprises SEQ ID NO:249, and the heavy chain comprises SEQ ID NO:210 or SEQ ID NO:211; or (w) The light chain comprises SEQ ID NO:250, and the heavy chain comprises SEQ ID NO:212 or SEQ ID NO:213; or (x) The light chain comprises SEQ ID NO:251, and the heavy chain comprises SEQ ID NO:214 or SEQ ID NO:215; or (y) The light chain comprises SEQ ID NO:252, and the heavy chain comprises SEQ ID NO:216 or SEQ ID NO:217; or (z) The light chain comprises SEQ ID NO:253, and the heavy chain comprises SEQ ID NO:218 or SEQ ID NO:219; or (aa) The light chain comprises SEQ ID NO:254, and the heavy chain comprises SEQ ID NO:220 or SEQ ID NO:221; or (ab) The light chain comprises SEQ ID NO:255, and the heavy chain comprises SEQ ID NO:222 or SEQ ID NO:223; or (ac) The light chain comprises SEQ ID NO:256, and the heavy chain comprises SEQ ID NO:224 or SEQ ID NO:225; or (ad) The light chain comprises SEQ ID NO:257, and the heavy chain comprises SEQ ID NO:226 or SEQ ID NO:227; or (ae) The light chain comprises SEQ ID NO:228, and the heavy chain comprises SEQ ID NO:364 or SEQ ID NO:365; or (af) The light chain comprises SEQ ID NO:229, and the heavy chain comprises SEQ ID NO:366 or SEQ ID NO:367; or (ag) The light chain comprises SEQ ID NO:230, and the heavy chain comprises SEQ ID NO:368 or SEQ ID NO:369; or (ah) The light chain comprises SEQ ID NO: 231, and the heavy chain comprises SEQ ID NO: 370 or SEQ ID NO: 371; or (ai) The light chain comprises SEQ ID NO: 232, and the heavy chain comprises SEQ ID NO: 372 or SEQ ID NO: 373; or (aj) The light chain comprises SEQ ID NO: 233, and the heavy chain comprises SEQ ID NO: 374 or SEQ ID NO: 375; or (ak) The light chain comprises SEQ ID NO: 234, and the heavy chain comprises SEQ ID NO: 376 or SEQ ID NO: 377; or (al) The light chain comprises SEQ ID NO: 235, and the heavy chain comprises SEQ ID NO: 378 or SEQ ID NO: 379; or (am) The light chain comprises SEQ ID NO: 236, and the heavy chain comprises SEQ ID NO: 380 or SEQ ID NO: 381; or (an) The light chain comprises SEQ ID NO: 237, and the heavy chain comprises SEQ ID NO: 382 or SEQ ID NO: 383; or (ao) The light chain comprises SEQ ID NO: 238, and the heavy chain comprises SEQ ID NO: 384 or SEQ ID NO: 385; or (ap) The light chain comprises SEQ ID NO: 239, and the heavy chain comprises SEQ ID NO: 386 or SEQ ID NO: 387; or (aq) The light chain comprises SEQ ID NO: 240, and the heavy chain comprises SEQ ID NO: 388 or SEQ ID NO: 389; or (ar) The light chain comprises SEQ ID NO: 241, and the heavy chain comprises SEQ ID NO: 390 or SEQ ID NO: 391; or (as) The light chain comprises SEQ ID NO: 242, and the heavy chain comprises SEQ ID NO: 392 or SEQ ID NO: 393; or (at) The light chain comprises SEQ ID NO: 243, and the heavy chain comprises SEQ ID NO: 394 or SEQ ID NO: 395; or (au) The light chain comprises SEQ ID NO: 244, and the heavy chain comprises SEQ ID NO: 396 or SEQ ID NO: 397; or (av) The light chain comprises SEQ ID NO: 245, and the heavy chain comprises SEQ ID NO: 398 or SEQ ID NO: 399; or (aw) The light chain comprises SEQ ID NO: 246, and the heavy chain comprises SEQ ID NO: 400 or SEQ ID NO: 401; or (ax) The light chain comprises SEQ ID NO: 247, and the heavy chain comprises SEQ ID NO: 402 or SEQ ID NO: 403; or (ay) The light chain comprises SEQ ID NO: 248, and the heavy chain comprises SEQ ID NO: 404 or SEQ ID NO: 405; or (az) The light chain comprises SEQ ID NO: 249, and the heavy chain comprises SEQ ID NO: 406 or SEQ ID NO: 407; or (ba) The light chain comprises SEQ ID NO: 250, and the heavy chain comprises SEQ ID NO: 408 or SEQ ID NO: 409; or (bb) The light chain comprises SEQ ID NO: 251, and the heavy chain comprises SEQ ID NO: 410 or SEQ ID NO: 411; or (bc) The light chain comprises SEQ ID NO: 252, and the heavy chain comprises SEQ ID NO: 412 or SEQ ID NO: 413; or (bd) The light chain comprises SEQ ID NO: 253, and the heavy chain comprises SEQ ID NO: 414 or SEQ ID NO: 415; or (be) The light chain comprises SEQ ID NO: 254, and the heavy chain comprises SEQ ID NO: 416 or SEQ ID NO: 417; or (bf) The light chain comprises SEQ ID NO: 255, and the heavy chain comprises SEQ ID NO: 418 or SEQ ID NO: 419; or (bg) The light chain comprises SEQ ID NO: 256, and the heavy chain comprises SEQ ID NO: 420 or SEQ ID NO: 421; or (bh) The light chain comprises SEQ ID NO: 257, and the heavy chain comprises SEQ ID NO: 422 or SEQ ID NO:

423.

31. An antibody or an antigen-binding fragment thereof, wherein the antibody comprises: A variable heavy chain comprising HCDR1 of SEQ ID NO:61, HCDR2 of SEQ ID NO:62, and HCDR3 of DX 10 X 11 X 12 YX 13 X 14 DX 15 (SEQ ID NO:329), wherein: X 10 is E, Q or N; X 11 is T, E, S or N; X 12 is D or Q; X 13 is A or G; X 14 is L, W, F or Y; and X 15 is Y, E, L, N, F or W; and A variable light chain comprising LCDR1 of SEQ ID NO:64, LCDR2 of SEQ ID NO:65, and an LCDR3 comprising the amino acid sequence X 16 X 17 X 18 EDX 19 X 20 X 21 X 22 (SEQ ID NO:328), where X 16 is Q, E, K or H; X 17 is Q or H; X 18 is Y or H, X 19 is L or Y; X 20 is P or I; X 21 is L or P, and X 22 is T or V.

32. An isolated nucleic acid molecule encoding the antibody or an antigen-binding fragment thereof, heavy chain variable region, light chain variable region, heavy chain or light chain according to any one of the preceding claims.

33. An expression vector comprising the nucleic acid molecule according to claim 32.

34. A host cell comprising the nucleic acid molecule according to claim 32 or the vector according to claim 33.

35. A pharmaceutical composition comprising the antibody or an antigen-binding fragment thereof according to any one of claims 1 to 17 and a pharmaceutically acceptable excipient.

36. A pharmaceutical composition comprising the antibody or an antigen-binding fragment thereof according to claim 18 and a pharmaceutically acceptable excipient.

37. A pharmaceutical composition comprising the antibody or an antigen-binding fragment thereof according to claim 19 and a pharmaceutically acceptable excipient.

38. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof according to any one of claims 20 to 31 and a pharmaceutically acceptable excipient.

39. A pharmaceutical composition according to any one of claims 35 to 38, wherein the composition is formulated for intravenous or subcutaneous injection.

40. A method of producing a polypeptide comprising a heavy chain variable region or a light chain variable region, the method comprising: (a) growing the host cell according to claim 34 under conditions such that the host cell expresses a polypeptide comprising the heavy chain variable region or the light chain variable region; and (b) purifying the polypeptide comprising the heavy chain variable region and / or the light chain variable region.

41. A method of treating a subject suffering from a C1s-mediated disorder, the method comprising administering to the subject the antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a pharmaceutical composition comprising the same.

42. A method of treating a subject suffering from a C1s-mediated disorder, the method comprising administering to the subject the antibody or antigen-binding fragment thereof according to any one of claims 18 to 31, or a pharmaceutical composition comprising the same.

43. The method according to claim 41 or 42, wherein the disorder is myasthenia gravis, hemolysis, cold agglutinin disease, immune thrombocytopenia (ITP), glomerulopathy, atypical hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), dermatomyositis or anti-MAG neuropathy.

44. A method of treating a subject suffering from myasthenia gravis or cold agglutinin disease, the method comprising administering to the subject the antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, or a pharmaceutical composition comprising the same.

45. The method according to claim 44, wherein the antibody or antigen-binding fragment thereof comprises a variable heavy chain region having the amino acid sequence of SEQ ID NO: 342 and a light chain variable region having the sequence of SEQ ID NO:

18.

46. The method according to claim 45, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain having the sequence of SEQ ID NO: 381 and a light chain having the sequence of SEQ ID NO:

236.

47. A method of inhibiting membrane attack complex (MAC) formation or deposition in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject the antibody or antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

48. A method of inhibiting or preventing nerve conduction damage in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject the antibody or antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

49. A method of enhancing, promoting, or allowing muscle contraction in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

50. A method of alleviating or relieving muscle paralysis in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

51. A method of inhibiting muscle tone or muscle mass loss in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

52. A method of reducing the muscle fatigue index in a subject in need thereof (e.g., a patient suffering from myasthenia gravis), the method comprising administering to the subject an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 31, or a pharmaceutical composition comprising the same.

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