Antibodies comprising common light chain and uses thereof

Abstract

To provide peptides that can act as light chains for antibodies and can be combined with a variety of heavy chains regardless of the target that the heavy chain binds to.SOLUTION: The present invention provides a protein and pharmaceutical compositions and uses thereof, the protein comprising: a first amino acid sequence or a first CDR selected from a group consisting of specific amino acid sequences, or a variant of any of the foregoing; a second amino acid sequence or a second CDR selected from a group consisting of specific amino acid sequences, or a variant of any of the foregoing; and a third amino acid sequence or a third CDR selected from a group consisting of specific amino acid sequences, or a variant of any of the foregoing.SELECTED DRAWING: None

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 806,052, filed on February 15, 2019, which is hereby incorporated by reference in its entirety.

Background Art

[0002] Antibodies have a well - defined structure and often will have a combination of what are called V H and V L domains. The domains may be in the conventional "Y" - shaped structure where the antibody has two V H and two V L peptides. Alternatively, the antibody may be in the form of a scFv where the V H and V L peptides are expressed as a fusion protein and there may be one each of V H and V L . The binding specificity of an antibody has been thought to be determined by the CDRs of each peptide that binds to the antigen of interest. However, it is useful for generating general peptides that can be used regardless of the target and can increase the plasticity in generating antibodies with different specificities for the same or different targets. The present disclosure provides these and other needs.

Summary of the Invention

[0003] In some embodiments, peptides, antibodies, compositions, nucleic acid molecules and other types of molecules as described herein are provided.

[0004] In some embodiments, provided is a protein comprising: a first amino acid sequence or a first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, and 76; a second amino acid sequence or a second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, and 79; and a third amino acid sequence or a third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80.

[0005] In some embodiments, provided is a protein comprising a sequence that is at least, or about, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 2 (F10h), SEQ ID NO: 1 (F10), SEQ ID NO: 3 (B9), SEQ ID NO: 4 (B9h), SEQ ID NO: 5 (N6-G3), SEQ ID NO: 6 (N6-C5), SEQ ID NO: 7 (N6-F11), SEQ ID NO: 8 (N5-B4), or SEQ ID NO: 9 (N5-B7), or the sequences of SEQ ID NOs: 18 - 80 and 84.

Mode for Carrying Out the Invention

[0006] Described and disclosed herein are peptides that can act as the light chain of an antibody and can be combined with various heavy chains regardless of the target to which the heavy chain binds.

[0007] This heavy chain may be referred to as a variable heavy chain (V H ). In some embodiments, V H can be a human, mouse, chicken, or humanized V H peptide.

[0008] As used herein, the term "antibody" is meant in a broad sense and includes immunoglobulins or antibody molecules, such as polyclonal antibodies, monoclonal antibodies, such as mouse, human, humanized, and chimeric monoclonal antibodies, and antibody fragments.

[0009] As used herein, the terms “humanized antibody,” “engineered antibody,” “human framework compliant,” and “HFA” shall include antibodies having variable region frameworks derived from sequences of human origin. Further, if the antibody includes a constant region, this constant region may be derived from such human sequences, such as human germline sequences, or naturally occurring (e.g., allotypes) or mutated versions of human germline sequences. A humanized antibody may include amino acid residues not encoded by human sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro or by somatic mutation in vivo).

[0010] Generally, an antibody is a protein or polypeptide that exhibits binding specificity for a particular antigen. An intact antibody is a heterotetrameric glycoprotein composed of two identical light chains and two identical heavy chains. Typically, each light chain is linked to a heavy chain by one covalent disulfide bond, although the number of disulfide bonds varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (V H ) at one end, followed by a number of constant domains. Each light chain has a variable domain at one end (V L ) and a constant domain at the other end, and the constant domain of this light chain is aligned with the first constant domain of the heavy chain, and this light chain variable domain is aligned with the variable domain of the heavy chain. The light chains of antibodies of any vertebrate species can be assigned to one of two clearly distinct types called kappa and lambda based on the amino acid sequence of their constant domains. Immunoglobulins can be assigned to five major classes, namely IgA, IgD, IgE, IgG, and IgM, depending on the amino acid sequence of the heavy chain constant domains. IgA and IgG are further subclassified such as IgA 1 , IgA 2 , IgG 1 , IgG 2 , IgG 3 and IgG 4 .

[0011] As used herein, unless otherwise specified, "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 to an antigen bound by the full-length antibody, for example, a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab’, F(ab’) 2 , and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules, e.g., sc-Fv; nanobodies; and multispecific antibodies formed from antibody fragments.

[0012] "Fab fragment" consists of one light chain and the variable regions of the C H1 and one heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0013] The "Fc" region contains two heavy chain fragments that include the C H1 and C H2 domains. The two heavy chain fragments are held together by two or more disulfide bonds and hydrophobic interactions of the C H 3 domain.

[0014] "Fab" fragment" includes one light chain and a part or fragment of one heavy chain, which is the V H domain and the C H1 domain, and also includes the region between the C H1 and C H2 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.

[0015] "F(ab’) 2 fragment" includes two light chains and two heavy chains, which are the C H1 domain and the C H2It includes a part of the constant region between domains, as a result, an inter-chain disulfide bond is formed between the two heavy chains. Therefore, AF(ab’) 2 The fragment is composed of two Fab’ fragments held together by a disulfide bond between the two heavy chains.

[0016] The "Fv region" contains variable regions derived from both the heavy and light chains, but lacks the constant region.

[0017] The term "single-chain Fv" or "scFv" antibody refers to an antibody fragment that contains the V H and V L domains, and these domains are present within a single polypeptide chain. Generally, the Fv polypeptide further contains a polypeptide linker between the V H and V L domains, which enables the scFv to form a structure desirable for antigen binding. For an overview of scFv, see Pluckthun (1994) The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenberg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also International Patent Application Publication No. WO88 / 01649 and U.S. Patent Nos. 4,946,778 and 5,260,203.

[0018] A "domain antibody" is an immunologically functional immunoglobulin fragment that contains only the variable region of the heavy chain or the variable region of the light chain. In some cases, two or more V H regions are covalently linked to a peptide linker to create a bivalent domain antibody. The two V H regions of the bivalent domain antibody can target the same or different antigens.

[0019] 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).

[0020] In certain embodiments, the monoclonal antibodies herein also include camelized single domain antibodies. See, for example, Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO94 / 04678; WO94 / 25591; U.S. Patent No. 6,005,079). In some embodiments, a provided single domain antibody is formed such that a modified two V H domains form a single domain antibody. In some embodiments, the V H domains are combined with V L domains such as those provided herein.

[0021] As used herein, the term "diabody" refers to a small antibody fragment having two antigen-binding sites, and these fragments are heavy chain variable domains (V L ) connected to light chain variable domains (V H ) within the same polypeptide chain (V H -V L or V L -V H ). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are paired with complementary domains on another chain to generate two antigen-binding sites. Diabodies are described in more detail, for example, in European Patent No. 404,097; WO 93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448. For a review of engineered antibody variants, generally see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0022] As used herein, the term "antigen" means any molecule having the ability to directly or indirectly generate an antibody. The definition of "antigen" includes nucleic acids encoding proteins. An antigen can also refer to a target bound by an antibody or a protein.

[0023] "CDR" is defined as the amino acid sequence of the complementarity-determining regions of an antibody, which are the hypervariable regions of the immunoglobulin heavy and light chains. See, for example, Kabat et al., Sequences of Proteins of Immunological Interest, 4th ed., U.S. Department of Health and Human Services, National Institutes of Health (1987). The variable portion of an immunoglobulin has three heavy-chain and three light-chain CDRs or CDR regions. Thus, as used herein, "CDR" refers to, as appropriate, all three heavy-chain CDRs, or all three light-chain CDRs, or both all heavy-chain and all light-chain CDRs.

[0024] CDRs provide most of the contact residues for binding an antibody to an antigen or epitope. The CDRs of interest may be derived from the variable heavy and light chain sequences of a donor antibody, and may include analogs of naturally occurring CDRs, which also share or retain the same antigen-binding specificity and / or neutralizing ability as the donor antibody from which they are derived. In some embodiments, the CDRs present in the V H domain determine what the antibody binds to, and the CDRs present in a common light chain do not significantly contribute to the binding specificity to the target.

[0025] The term "identity" means a protein sequence having 40% to 100% sequence identity to 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 Vector NTI v.9.0.0 (Invitrogen Corp., Carslbad, Calif.). In some embodiments, the antibody or fragment thereof has at least 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the sequences described herein, such as the sequences of SEQ ID NOs: 1-9 or SEQ ID NOs: 18-80, or 84. These may also be referred to as variants. In some embodiments, this sequence or variant has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions as compared to the sequences provided herein. In some embodiments, the substitutions are conservative substitutions. In some embodiments, the mutation or substitution is in the framework region of the light chain. In some embodiments, the substitution is in a CDR region such as CDR1, CDR2, or CDR3. In some embodiments, the mutation or substitution is in CDR1 rather than CDR2 or CDR3. In some embodiments, the light chain contains a substitution or change in the framework region rather than in the CDR regions as provided herein. In some embodiments, a light chain or protein is provided that is at least or about 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NOs: 1-9, provided that this sequence does not contain a first amino acid sequence or first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, 76 and 84; a second amino acid sequence or second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, and 79; and a third amino acid sequence or third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80. Thus, in some embodiments, the CDRs are not variants of those provided herein.In some embodiments, the antibody has conservative substitutions compared to the sequences described herein. Antibodies having conservative substitutions in the heavy and light chain sequences shown in Table 1 are included within the scope of the disclosed subject matter. Conservative substitutions may be present in the framework regions or in the antigen-binding sites, so long as they do not adversely affect the properties of the antibody. Substitutions may be made to improve properties of the antibody, such as stability or affinity. Conservative substitutions result in molecules having functional and chemical properties similar to those of the molecule in which such modifications are made. Exemplary amino acid substitutions are shown in the following table.

Table 1

[0026] As used herein, the term "in combination with" means that the described agent(s) can be administered to an animal in any order, together in a mixture, simultaneously as a single agent, or sequentially as a single agent.

[0027] Polyclonal antibodies are a heterogeneous population of antibody molecules derived from the sera of animals immunized with an antigen. Monoclonal antibodies include a substantially homogeneous population of antibodies specific for an antigen, the population containing substantially similar epitope binding sites. MAbs may be obtained by methods known to those skilled in the art. For example, see Kohler and Milstein, Nature 256:495-497 (1975); U.S. Patent No. 4,376,110; Ausubel et al., eds., Current Protocols in Molecular Biology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1987, 1992); as well as Harlow and Lane ANTIBODIES: A Laboratory Manual Cold Spring Harbor Laboratory (1988); Colligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1992, 1993), the contents of which are hereby incorporated by reference in their entirety. Such antibodies can be of any immunoglobulin class including IgG, IgM, IgE, IgA, GILD and any of their subclasses. Hybridomas producing mAbs can be cultured in vitro, in situ, or in vivo. Production of high-titer mAbs in vivo or in situ has now become the preferred production method.

[0028] Chimeric antibodies are molecules in which different parts are derived from different animal species, for example, those having a variable region derived from a murine mAb and a human immunoglobulin constant region, and these are mainly used to reduce immunogenicity in application and increase yield in production. For example, murine mAbs have a high yield from hybridomas but are highly immunogenic in humans, so human / murine chimeric mAbs are used. Chimeric antibodies and methods for their production are known in the art (Cabilly et al., Proc. Natl. Acad. Sci. USA 81:3273 3277 (1984); Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851 6855 (1984); Boulianne et al., Nature 312:643 646 (1984); Cabilly et al., European Patent Application 125023 (published Nov. 14, 1984); Neuberger et al., Nature 314:268 270 (1985); Taniguchi et al., European Patent Application 171496 (published Feb. 19, 1985); Morrison et al., European Patent Application 173494 (published Mar. 5, 1986); Neuberger et al., PCT Application WO 86 / 01533, (published Mar. 13, 1986); Kudo et al., European Patent Application 184187 (published Jun. 11, 1986); Morrison et al., European Patent Application 173494 (published Mar. 5, 1986); Sahagan et al., J. Immunol. 137:1066 1074 (1986); Robinson et al., International Patent Publication No. WO1987 / 002671 (published May 7, 1987); Liu et al., Proc. Natl. Acad. Sci. USA 84:3439 3443 (1987); Sun et al., Proc. Natl. Acad. Sci. USA 84:214 - 218 (1987); Better et al., Science 240:1041 - 1043 (1988); and Harlow and Lane Antibodies, a Laboratory Manual, Cold Spring Harbor Laboratory (1988)). These references are hereby incorporated by reference in their entirety into this specification.

[0029] Anti - idiotypic (anti - Id) antibodies are antibodies that recognize unique determinants generally associated with the antigen - binding site of an antibody. Id antibodies can be prepared by immunizing animals of the same species and genotype as the source of the mAb (e.g., a mouse strain) with the mAb against which the anti - Id is to be prepared. The immunized animals will recognize and respond to the idiotypic determinants of the immunizing antibody by producing antibodies (anti - Id antibodies) against these idiotypic determinants. See, for example, U.S. Patent No. 4,699,880, which is hereby incorporated by reference in its entirety into this specification. Anti - Id antibodies can also be used as an "immunogen" to induce an immune response in yet another animal, producing so - called anti - anti - Id antibodies. The anti - anti - Id can be epitopically identical to the original mAb that induced the anti - Id. Thus, by using antibodies against the idiotypic determinants of an mAb, it is possible to identify other clones expressing antibodies of the same specificity.

[0030] As used herein, the term "monoclonal antibody" (mAb) means an antibody (or antibody fragment) obtained from a substantially homogeneous population of antibodies. Monoclonal antibodies are highly specific and typically target a single antigenic determinant. The modifier "monoclonal" indicates the substantially homogeneous nature of the antibody and does not require the antibody to be produced by any particular method. For example, murine mAbs may be produced by the hybridoma method of Kohler et al., Nature 256:495-497 (1975). Chimeric mAbs that include light and heavy chain variable regions derived from a donor antibody (typically murine) and light and heavy chain constant regions related to an acceptor antibody (typically another mammalian species such as human) may be prepared by the method disclosed in U.S. Patent No. 4,816,567 Humanized mAbs having CDRs derived from non-human donor immunoglobulins (usually murine) and the remaining immunoglobulin-derived portions of the molecule derived from one or more human immunoglobulins and having framework support residues modified optionally to maintain binding affinity may be obtained by the techniques disclosed in Queen et al., Proc. Natl. Acad. Sci. (USA), 86:10029-10032 (1989) and Hodgson et al., Bio / Technology, 9:421 (1991).

[0031] As used herein, the term "humanized antibody" refers to an antibody form that includes sequences derived from both human and non-human (e.g., murine, rat, chicken) antibodies. Generally, a humanized antibody includes substantially all of at least one, typically two, variable domains, with all or substantially all of the hypervariable loops corresponding to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions being those of a human immunoglobulin sequence. A humanized antibody may optionally include at least a portion of a human immunoglobulin constant region (Fc).

[0032] The term "fully human antibody" refers to an antibody that contains only human immunoglobulin protein sequences. A fully human antibody may contain mouse carbohydrate chains if it is produced by a mouse, mouse cells, or a hybridoma derived from mouse cells. Similarly, a "mouse antibody" refers to an antibody that contains only mouse immunoglobulin sequences. Alternatively, a fully human antibody may contain rat carbohydrate chains if it is produced by a rat, rat cells, or a hybridoma derived from rat cells. Similarly, a "rat antibody" refers to an antibody that contains only rat immunoglobulin sequences. Similarly, a "chicken antibody" refers to an antibody that contains only chicken immunoglobulin sequences. For example, the term "chicken antibody" refers to an antibody produced in a chicken. For example, a protein of interest may be introduced into a chicken, such as a VLP, to stimulate an immune response against the protein of interest and produce an antibody in the chicken. Next, the antibody may be humanized or, if not, modified as necessary.

[0033] In addition to the antibodies described herein, exemplary human framework sequences useful for humanization are disclosed, for example, at the following: www“dot”ncbi“dot”nlm“dot”nih“dot”gov / entrez / query“dot”fcgi;www“dot”ncbi“dot”nih“dot”gov / igblast;www“dot”atcc“dot”org / phage / hdb“dot”html;www“dot”mrc-cpe“dot”cam“dot”ac“dot”uk / ALIGNMENTS“dot”php;“dot” www“dot”kabatdatabase“dot”com / top“dot”html;ftp“dot”ncbi“dot”nih“dot”gov / repository / kabat;www“dot”sciquest“dot”com;www“dot”abcam“dot”com;www“dot”antibodyresource“dot”com / onlinecomp“dot”html;www“dot”public“dot”iastate“dot”edu / “dot”about“dot”pedro / research_tools“dot”html;www“dot”whfreeman“dot”com / immunology / CH05 / kuby05“dot”htm;www“dot”hhmi“dot”org / grants / lectures / 1996 / vlab;www“dot”path“dot”cam“dot”ac“dot”uk / “dot”about“dot”mrc7 / mikeimages“dot”html;mcb“dot”harvard“dot”edu / BioLinks / Immunology“dot”html;www“dot”immunologylink“dot”com;pathbox“dot”wustl“dot”edu / “dot”about“dot”hcenter / index“dot”html;www“dot”appliedbiosystems“dot” com; www “dot” nal “dot” usda “dot” gov / awic / pubs / antibody; www “dot” m “dot” ehime - u “dot” ac “dot” jp / “dot” about “dot” yasuhito / Elisa “dot” html; www “dot” biodesign “dot” com; www “dot” cancerresearchuk “dot” org; www “dot” biotech “dot” ufl “dot” edu; www “dot” isac - net “dot” org; baserv “dot” uci “dot” kun “dot” nl / “dot” about “dot” jraats / links1 “dot” html; www “dot” recab “dot” uni - hd “dot” de / immuno “dot” bme “dot” nwu “dot” edu; www “dot” mrc - cpe “dot” cam “dot” ac “dot” uk; www “dot” ibt “dot” unam “dot” mx / vir / V_mice “dot” html; http: / / www “dot” bioinf “dot” org “dot” uk / abs; antibody “dot” bath “dot” ac “dot” uk; www “dot” unizh “dot” ch; www “dot” cryst “dot” bbk “dot” ac “dot” uk / “dot” about “dot” ubcg07s; www “dot” nimr “dot” mrc “dot” ac “dot” uk / CC / ccaewg / ccaewg “dot” html; www “dot” path “dot” cam “dot” ac “dot” uk / “dot” about “dot” mrc7 / humanisation / TAHHP “dot” html; www “dot” ibt “dot” unam “dot” mx / vir / structure / stat_aim “dot” html; www “dot” biosci “dot” missouri “dot” edu / smithgp / index “dot” html; www “dot” jerini “dot” de; imgt “dot” cines “dot” fr; and Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Dept.Health(1987)(each of which is hereby incorporated by reference in its entirety). The "dot" in the World Wide Web addresses referred to herein may be replaced by "." as appropriate.

[0034] Generally, the basic antibody structural unit contains a tetramer. Each tetramer contains two identical polypeptide chain pairs, and each pair has one "light chain" (about 25 kDa) and one "heavy chain" (about 50 - 70 kDa). The amino-terminal portion of each chain contains a variable region of about 100 - 110 or more amino acids that is mainly involved in antigen recognition. The carboxy-terminal portion of this heavy chain may define a constant region mainly responsible for effector functions. Usually, human light chains are classified into kappa light chains and lambda light chains. Further, human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and are defined as antibody isotypes 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, and the heavy chain also contains a "D" region of about 10 or more amino acids. Generally, see Fundamental Immunology Ch.7 (Paul, W., ed., 2nd ed. Raven Press, N.Y. (1989).

[0035] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, generally, intact antibodies have two binding sites. Except for bifunctional or bispecific antibodies, the two binding sites are generally the same.

[0036] The term "hypervariable region", as used herein, refers to the amino acid residues of an antibody that are involved in antigen binding. The hypervariable regions are amino acid residues derived 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 to 35 (CDRH1), 50 to 65 (CDRH2), and 95 to 102 (CDRH3); Kabat et al., (1991) Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md.) and / or those residues derived from "hypervariable loops" (i.e., residues 26 to 32 (CDRL1), 50 to 52 (CDRL2), and 91 to 96 (CDRL3) in the light chain variable domain and 26 to 32 (CDRH1), 53 to 55 (CDRH2), and 96 to 101 (CDRH3) in the heavy chain variable domain; Chothia and Lesk (1987) J. Mol. Bio. 196:901-917). As used herein, the term "framework" or "FR" residues refers to those variable domain residues other than the hypervariable region residues defined herein such as CDR residues. CDRs provide most of the contact residues for binding of an antibody to an antigen or epitope. The CDRs of interest may be derived from the variable heavy and light chain sequences of a donor antibody and may include analogs of naturally occurring CDRs, which also share or retain the same antigen-binding specificity and / or neutralizing capacity as the donor antibody from which they are derived.

[0037] Furthermore, in some embodiments, the antibody may be in the form of a full-length antibody, single-domain antibody, single-chain antibody (scFv), microprotein (cysteine knot protein, knottin), DARPin; tetranectin; affibody; transbody; anticalin; AdNectin; affilin; microbody; peptide aptamer; altarease; plastic antibody; filomer; stradbody; maxibody; evibody; finomer, armadillo repeat protein, knotted domain, avimer, atrimer, probody, immunobody, triomab, tribody; pepbody; vaccibody, UniBody; affimer, DuoBody, Fv, Fab, Fab’, F(ab’)2, peptide mimetic molecule, or synthetic molecule, as described in U.S. Patent No. or Patent Publication No. 7,417,130, U.S. Patent Application Publication No. 2004 / 132094, U.S. Patent No. 5,831,012, U.S. Patent Application Publication No. 2004 / 023334, U.S. Patent No. 7,250,297, U.S. Patent No. 6,818,418, U.S. Patent Application Publication No. 2004 / 209243, U.S. Patent No. 7,838,629, U.S. Patent No. 7,186,524, U.S. Patent No. 6,004,746, U.S. Patent No. 5,475,096, U.S. Patent Application Publication No. 2004 / 146938, U.S. Patent Application Publication No. 2004 / 157209, U.S. Patent No. 6,994,982, U.S. Patent No. 6,794,144, U.S. Patent Application Publication No. 2010 / 239633, U.S. Patent No. 7,803,907, U.S. Patent Application Publication No. 2010 / 119446, and / or U.S. Patent No. 7,166,697, the contents of each of which are hereby incorporated by reference in their entirety. See also Storz MAbs. 2011 May-Jun;3(3):310-317, which is hereby incorporated by reference.

[0038] In some embodiments, the antibodies described herein may include, but are not limited to, a heavy chain constant region (H c ), a heavy chain variable region (H v ), a light chain variable region (L v ), and a light chain constant region (Lc ) may include at least one of, wherein the polyclonal Ab, monoclonal Ab, fragment and / or its region comprises at least one heavy chain variable region (H v ) or light chain variable region (L v ). This L v may also be referred to as V L . This H v may also be referred to as V H . The antibody may also be a monoclonal antibody made by immunizing a chicken. The variable chain derived from the nucleic acid sequence encoding the isolated monoclonal antibody can be isolated, but not limited to, by using techniques such as PCR. The variable chains isolated by these techniques can then be placed in an scFv vector containing human Fc. Thus, the antibody may be an antibody having human Fc and two scFv arms. Next, the antibodies as described throughout this specification and the present disclosure can be modified to be human or humanized antibodies. Examples of methods for modifying antibodies including chicken antibodies can be found, for example, in Riechmann L, Clark M, Waldmann H, Winter G (1988) "Reshaping human antibodies for therapy". Nature 332(6162):332 - 323; Tsurushita N, Park M, Pakabunto K, Ong K, Avdalovic A, Fu H, Jia A, Vasquez M, Kumar S. (2004); and "Humanization of a chicken anti - IL - 12 monoclonal antibody" Immunol Methods 295(1 - 2):9 - 19; Nishibori N, Horiuchi H, Furusawa S, Matsuda H. (2006) "Humanization of chicken monoclonal antibody using phage display system" Mol Immunol. 43(6):634 - 42, each of which is incorporated by reference in its entirety). ).

[0039] Methods for determining the specificity and affinity of mAbs by competitive inhibition can be found in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1988), Colligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1992, 1993), and Muller, Meth. Enzymol. 92:589 601(1983) (these references are hereby incorporated by reference in their entirety into this specification).

[0040] Techniques for producing antibodies that recognize and bind to small peptide sequences, whether in free or conjugated form, or when presented as the native sequence in the context of a large protein, are well known in the art. Such antibodies include monoclonal antibodies or mouse, mouse - human and human - human antibodies produced by recombinant techniques known in the art. Antibodies can also be produced in chickens, goats, rabbits, or other small animals.

[0041] As used herein, the term "antigen - binding region" refers to that portion of an antibody molecule that interacts with an antigen (e.g., a target protein) and contains the amino acid residues that confer on the antibody its specificity and affinity for that antigen. The antibody region includes the "framework" amino acid residues necessary to maintain the proper tertiary structure of the antigen - binding residues. In some embodiments, the antigen - binding region is of murine origin. In some embodiments, the antigen - binding region can be derived from other animal species, specifically rodents such as rabbits, rats or hamsters, or birds such as chickens. It has been shown that the antigen - binding function of an antibody can be performed by fragments of the full - length antibody. Examples of binding fragments included within the term "antigen - binding portion" of an antibody include the Fab fragment, i.e., VL , V H , a monovalent fragment having a CL and CH1 domain; F(ab) 2 fragment, i.e., a divalent fragment comprising two Fab fragments linked by a disulfide bridge(s) in the hinge region; V H and an Fd fragment having a CH1 domain; V of a single arm of an antibody L and V H and an Fv fragment having a V domain; V H a domain antibody or dAb fragment consisting of a V domain (Ward et al., 1989 Nature 341:544 - 546); and isolated complementarity - determining regions (CDRs), particularly CDR3 (see, e.g., WO03 / 025019, the content of which is incorporated herein by reference) are included.

[0042] The term "complementarity - determining region (CDR)" is based on sequence variability (Wu and Kabat, J. Exp. Med. 132:211 - 250, 1970). There are six CDRs, three in the variable heavy chain or V H and are usually called H - CDR1, H - CDR2, and H - CDR3, and three CDRs are in the variable light chain or V L and are usually called L - CDR1, L - CDR2, and L - CDR3 (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). "Hypervariable region", "HVR", or "HV" refers to the region of an antibody variable domain that is variable in structure as defined by Chothia and Lesk (Chothia and Lesk, Mol. Biol. 196:901 - 917, 1987). There are six HVRs, three in V H (H1, H2, H3), and three in V LThey are at (L1, L2, L3). Chothia and Lesk refer to structurally conserved HVs as "canonical structures". Another way to describe the regions that form the antigen-binding site has been proposed by Lefranc (Lefranc et al., Developmental & Comparative Immunology 27:55-77, 2003) based on the comparison of V domains from immunoglobulins and T cell receptors (Lefranc et al., Developmental & Comparative Immunology 27:55-77, 2003). According to Almagro (Almagro, Mol. Recognit. 17:132-43, 2004), the antigen-binding site can also be depicted based on "Specificity Determining Residue Usage" (SDRU), where SDRU refers to the amino acid residues of the immunoglobulin that are directly involved in antigen contact).

[0043] Furthermore, the two domains of the Fv fragment, V L and V H are naturally encoded by separate genes, but they can be joined by a synthetic linker using recombinant methods that enable them to be made as a single protein chain, where the V L and V H regions pair to form a monovalent molecule (known as a single-chain Fv (scFv); see, for example, Bird et al., Science 1988, 242, 423-426; and Huston et al., 1988 Proc. Nat. Acad. Sci. 85:5879-5883). Such single-chain antibodies are encompassed by the term "antigen-binding portion" of an antibody. These antibody fragments can be obtained using conventional techniques known to those skilled in the art and can be used in the same manner as intact antibodies.

[0044] As used herein, an "isolated antibody" refers to an antibody that substantially lacks other antibodies having different antigen specificities. Additionally, an isolated antibody may substantially lack other cellular and / or chemical substances. An isolated antibody may also be sterile or pyrogen-free, or formulated as an injectable pharmaceutical as described herein.

[0045] In some embodiments, the source of DNA encoding a non-human antibody includes a cell line that produces an antibody, such as a hybrid cell line commonly known as a hybridoma.

[0046] An "antigen" can be a molecule or a portion of a molecule that can be bound by an antibody that can further induce an animal to produce an antibody that can bind to an epitope of that antigen. An antigen can have one or more epitopes. The specific reaction described above means that the antigen reacts in a highly selective manner with the corresponding antibody, rather than with many other antibodies that can be induced by other antigens. In some embodiments, antibodies, fragments, and regions of antibodies bind to The antigen contains at least five amino acids. In some embodiments, the antigen is a target protein expressed on the surface of a cell or particle. In some embodiments, the cell is an intact cell. An intact cell is a cell that has not been lysed or disrupted using a surfactant or other reagent. A cell treated with a surfactant or other reagent that disrupts the cell membrane or makes holes in the cell membrane is not an intact cell. By expressing a receptor on the surface of a cell or particle, e.g., a lipoparticle, the receptor can present conformational epitopes that may not be present when a purified protein is used. Examples are provided herein. In some embodiments, an adjuvant is not used, but an adjuvant may be used. In some embodiments, the particle is injected into a bird (e.g., a chicken) to stimulate an immune response and generate antibodies against the protein present on the surface of the particle. Particles suitable for antibody production are described in U.S. Patent Nos. 8,377,691, 7,763,258, 8,158,130, and U.S. Patent Application Publication Nos. 20050123563 and 20120195882, each of which is incorporated herein by reference. These publications and patents describe the production of various particles, including lipoparticles, that can be used to express transmembrane proteins (e.g., multiple transmembrane proteins, ion channels, etc.).

[0047] The term "epitope" means that portion of any molecule that is recognized by an antibody in the antigen-binding region of one or more Abs and can be bound by the antibody. An epitope typically consists of chemically active surface moieties of a molecule, such as amino acids or sugar side chains, and has specific three-dimensional structural characteristics as well as specific charge characteristics. Examples of epitopes include, but are not limited to, the following

[0048] Hybrid cells are formed by the fusion of non-human antibody-producing cells, typically animal spleen cells, immunized against either a native or recombinant antigen, or a peptide fragment of an antigen protein sequence. Alternatively, the non-human antibody-producing cells may be B lymphocytes obtained from the blood, spleen, lymph nodes or other tissues of an animal immunized with an antigen.

[0049] The second fusion partner providing the immortalizing function may be a lymphoblastoid cell or a plasmacytoma or myeloma cell (which is not itself an antibody-producing cell but is malignant). Examples of fusion partner cells include, but are not limited to, hybridoma SP2 / 0-Ag14, abbreviated SP2 / 0 (ATCC CRL1581) and myeloma P3X63Ag8 (ATCC TIB9), or derivatives thereof. See, for example, Ausubel (below), Harlow (below), and Colligan (below) (the contents of these references are incorporated herein by reference in their entirety).

[0050] Antibodies can be generated according to the examples provided herein. Once the sequence is known, antibodies may be generated according to known methods. Antibodies may also be converted to different types, such as conversion to human IgG. By converting the antibody to a human antibody, the human subject must not recognize the antibody as foreign. This results in a more effective response. The conversion of non-human IgG antibodies to human IgG antibodies is well known and can be routinely performed once the native sequence is known. As discussed herein, antibodies can be modified according to known methods. Such methods include, for example, Riechmann L, Clark M, Waldmann H, Winter G (1988) "Reshaping human antibodies for therapy” Nature 332(6162):332-323; Tsurushita N, Park M, Pakabunto K, Ong K, Avdalovic A, Fu H, Jia A, Vasquez M, Kumar S. (2004); and “Humanization of a chicken anti-IL-12 monoclonal antibody” Immunol Methods 295(1-2):9-19; Nishibori N, Horiuch i H, Furusawa S, Matsuda H. (2006) “Humanization of chicken monoclonal antibody using phage display system” Mol Immunol. 43(6):634-42 (each of these is incorporated by reference in its entirety).

[0051] Antibody-producing cells that contribute to the nucleotide sequence encoding the antigen-binding region of a chimeric antibody can also be produced by transformation of non-human or human cells such as primates. For example, B lymphocytes that produce an antibody can be infected and transformed with a virus such as Epstein-Barr virus to produce immortal antibody-producing cells (Kozbor et al., Immunol. Today 4:72 79 (1983)). Alternatively, as is well known in the art, B lymphocytes can be transformed by providing a transforming gene or transforming gene product. For example, see Ausubel (below), Harlow (below), and Colligan (below), the contents of which are incorporated herein by reference in their entirety.

[0052] Cell fusion is achieved by standard procedures well known to those skilled in the art of immunology. Fusion partner cell lines and methods for fusing and selecting hybridomas and screening for mAbs are well known in the art. For example, see Ausubel (below), Harlow (below), and Colligan (below), the contents of which are incorporated herein by reference in their entirety.

[0053] Antigen-specific murine or chimeric mAbs can be produced in large quantities by injecting hybridoma or transfectoma cells secreting the antibody into the peritoneal cavity of a mouse, and after an appropriate time, collecting ascites containing high-titer mAb and isolating the mAb therefrom. For such in vivo production of mAbs using non-murine hybridomas (e.g., rat or human), the hybridoma cells are preferably grown in irradiated or athymic nude mice. Alternatively, the antibody can be produced recombinantly or isolated from cell culture medium in which hybridoma or transfectoma cells are cultured in vitro and the secreted mAb is isolated in eukaryotic or prokaryotic cells.

[0054] In some embodiments, the antibody is a MAb that binds to a target protein. In some embodiments, the antibody binds to the amino acids of an epitope of the target protein.

[0055] In some embodiments, the antibody comprises a sequence as provided herein.

[0056] The sequence of the antibody can be modified to generate a human IgG antibody. The conversions of the sequences provided herein can be modified to yield other types of antibodies. The CDRs can be linked to other antibodies, proteins, or molecules to create antibody fragments that bind to the target protein. The CDRs and antibody sequences provided herein can also be humanized or fully humanized according to known methods. This sequence can also be made into a chimeric antibody as described herein.

[0057] In some embodiments, the antibody comprises an amino acid sequence comprising the sequence provided herein or a fragment thereof. In some embodiments, the antibody comprises one or more amino acid sequences as provided herein, their antigen-binding fragments, or human IgG variants thereof. "Human IgG variants thereof" refers to antibodies modified to be human IgG when the starting antibody is not a human IgG antibody.

[0058] As described herein, the production of antibodies having known sequences is conventional and may be performed by any method. Thus, in some embodiments, nucleic acids encoding an antibody or a fragment thereof are provided. In some embodiments, the nucleic acid encodes a sequence provided herein. The antibody may also be modified to be a chimeric or human antibody. The antibody may also be used in an injectable pharmaceutical composition. As also described herein, the antibody may be an isolated antibody or an engineered antibody.

[0059] In some embodiments, a “derivative” of an antibody, fragment, region or a derivative thereof is provided, the term including a protein encoded by a truncated or modified gene to yield a molecular species that is functionally similar to an immunoglobulin fragment. Modifications include, but are not limited to, the addition of gene sequences encoding cytotoxic proteins such as plant and bacterial toxins. Modifications may also include reporter proteins such as fluorescent or chemiluminescent tags. Fragments and derivatives may be produced by any method.

[0060] Examples of fragments include Fab, Fab’, F(ab’) 2 , and Fv. These fragments lack the Fc fragment of the intact antibody, are removed more rapidly from the circulation, and may have lower non-specific tissue binding than intact antibodies (Wahl et al., J. Nucl. Med. 24:316 325 (1983)). These fragments are generated from intact antibodies using methods well known in the art, such as proteolytic cleavage with enzymes such as papain (to generate Fab fragments) or pepsin (to generate F(ab’) 2 fragments).

[0061] The identification of these antigen-binding regions and / or the epitopes recognized by the Abs described herein provides the information necessary to generate additional monoclonal antibodies having similar binding characteristics and therapeutic or diagnostic utility parallel to the embodiments of the present application.

[0062] A protein or antibody may also be provided as a nucleic acid sequence / molecule. The nucleic acid sequence encoding the antibody or protein described herein can be genomic DNA or cDNA, or RNA (e.g., mRNA) encoding at least one of the variable regions described herein. A convenient alternative to using chromosomal gene fragments as a source of DNA encoding V-region antigen-binding segments is, for example, the use of cDNA for the construction of chimeric immunoglobulin genes, as reported by Liu et al. (Proc. Natl. Acad. Sci., USA 84:3439 (1987) and J. Immunology 139:3521 (1987)), the references to which are hereby incorporated by reference in their entirety. The use of cDNA requires that appropriate gene expression elements be combined with the gene in a host cell to achieve synthesis of the desired protein. The use of cDNA sequences is advantageous over genomic sequences (including introns) in that cDNA sequences can be expressed in bacteria or other hosts lacking appropriate RNA splicing systems.

[0063] For example, a cDNA encoding a V-region antigen-binding segment that can detect, bind, bind to, or neutralize a target protein or antigen can be provided using known methods based on the use of the amino acid sequences provided herein. Since the genetic code is degenerate, multiple codons can be used to encode a particular amino acid (Watson, et al., below). Using the genetic code, one or more different oligonucleotides can be identified, each of which can encode an amino acid. The probability that a particular oligonucleotide actually constitutes the actual coding sequence is affected by abnormal base pair relationships and the actual use of particular codons in eukaryotic or prokaryotic cells expressing the antibody or fragment (encoding a particular amino acid It can be estimated by considering the frequency of such usage. Such "codon usage rules" are disclosed by Lathe, et al., J. Molec. Biol. 183:112 (1985). Using Lathe's "codon usage rules", a single oligonucleotide, or a set of oligonucleotides, containing the theoretically "most likely" nucleotide sequence that can encode the variable or constant region sequence of an antibody is identified.

[0064] The variable regions described herein can be combined with any type of constant region, including human or mouse constant regions. Human genes encoding the constant (C) regions of antibodies, fragments, and regions can be derived from a human fetal liver library by known methods. The human C region gene can be derived from any human cell, including cells that express and produce human immunoglobulins. The human C H region can be derived from any known class or isotype of human H chain, including gamma, mu, alpha, delta, or epsilon, and their subtypes, such as G1, G2, G3, and G4. Since H chain isotypes are involved in various effector functions of antibodies, the selection of the C H region is guided by the desired effector function, such as complement binding or antibody-dependent cell cytotoxicity (ADCC) activity. Preferably, the C H region is derived from gamma 1 (IgG1), gamma 3 (IgG3), gamma 4 (IgG4), or mu (IgM). The human C L region can be derived from either the human L chain isotype, kappa or lambda.

[0065] Genes encoding the human immunoglobulin C region can be obtained from human cells by standard cloning techniques (Sambrook, et al. (Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989) and Ausubel et al., eds. Current Protocols in Molecular Biology (1987 - 1993)). Human C region genes are readily available from known clones containing genes representing two classes of L chains, five classes of H chains and their subclasses. F(ab’) 2 Chimeric antibody fragments such as and Fab can be prepared by designing a chimeric H chain gene that is appropriately cleaved. For example, F(ab’) 2 The chimeric gene encoding the H chain portion of the fragment will contain a DNA sequence encoding the CH 1 domain and the hinge region, followed by a translation stop codon, and will generate a shortened molecule.

[0066] Generally, the mouse, human or mouse and chimeric antibodies, fragments and regions of antibodies described herein are generated by cloning DNA segments encoding the H and L chain antigen binding regions of antigen - specific antibodies, and by ligating these DNA segments to DNA segments encoding the C H and C L regions, respectively, to generate genes encoding mouse, human, or chimeric immunoglobulins.

[0067] Thus, in some embodiments, a fusion chimeric gene is created that includes a first DNA segment encoding at least an antigen - binding region of non - human origin, such as a functionally rearranged V region having a joining (J) segment, linked to a second DNA segment encoding at least a portion of the human C region.

[0068] Thus, the cDNA encoding the antibody V and C regions and the method for producing chimeric antibodies according to some of the embodiments described herein include several steps, as exemplified below: 1. Isolation of messenger RNA (mRNA) from a cell line that generates an anti - antigen antibody and optionally from additional antibodies (providing heavy and light constant regions); cloning and then cDNA generation; 2. Preparation of a full - length cDNA library from the purified mRNA, from which the appropriate V and / or C region gene segments of the L and H chain genes are: (i) identified with an appropriate probe, (ii) sequenced, and (iii) made compatible with the C or V gene segment from another antibody of the chimeric antibody; 3. Construction of the complete H or L chain coding sequence by ligating the cloned specific V region gene segment to the cloned C region gene as described above; 4. Expression and production of the L and H chains in a selected host, including prokaryotic and eukaryotic cells, to provide a mouse - mouse, human - mouse, human - human or human - mouse antibody.

[0069] One of the features common to all immunoglobulin H and L chain genes and their encoded mRNAs is the J region. The J regions of the H and L chains have different sequences, but there is a high degree of sequence homology (greater than 80%) among each group, particularly near the C region. This homology is utilized in this method to design oligonucleotides as primers to introduce restriction sites into the J region that are useful for subsequent ligation of the V region segment to the human C region segment.

[0070] The C region cDNA vector prepared from human cells may be modified by site - directed mutagenesis to place restriction sites at positions analogous to the human sequence. For example, the complete human kappa chain C (C k)The domain and the complete human gamma-1 C region (Cγ-1) can be cloned. In this case, in an alternative method based on genomic C region clones as a source of the C region vector, these genes cannot be expressed in a bacterial system that lacks the enzymes necessary to remove intervening sequences. The cloned V region segments are excised and ligated to the L or H chain C region vector. Alternatively, the human Cγ-1 region may be modified by introducing a stop codon, thereby generating a gene sequence encoding the H chain portion of the Fab molecule. Next, the coding sequence having the ligated V and C regions is transferred to an appropriate expression vehicle for expression in an appropriate prokaryotic or eukaryotic host.

[0071] Two coding DNA sequences are said to be "operably linked" when the ligation results in a sequence that can be continuously translated without a change or interruption in the triplet reading frame. A DNA coding sequence is operably linked to a gene expression element when the ligation results in the proper functioning of that gene expression element and results in the expression of the coding sequence.

[0072] Examples of expression vehicles include plasmids or other vectors. Preferred among these are any functional complete human C having appropriate restriction sites engineered to easily insert any V H or V L chain sequence, or any functional complete human C H or C L chain sequence that can easily insert the appropriate cohesive end. Thus, a vehicle containing a human C H or C L chain sequence functions as an intermediate for the expression of any desired complete H or L chain in any appropriate host.

[0073] Chimeric antibodies, such as mouse-human or human-human, are usually synthesized from genes driven by natural chromosomal promoters for the V regions of the mouse H and L chains used in the construct. Splicing usually occurs between the splice donor site of the mouse J region and the splice acceptor site preceding the human C region, and also occurs in the splice regions that occur within the human C region. Polyadenylation and transcription termination occur at natural chromosomal sites downstream of the human coding region.

[0074] As used herein, unless otherwise specified, the term "about" is intended to mean ±5% of the value it modifies. Thus, about 100 means 95 - 105.

[0075] In some embodiments, the antibodies described herein are used to detect the presence of an antigen. The antibodies of the invention can be used in any device or method for detecting the presence of an antigen. be used

[0076] The term "purified" when referring to an antibody refers to an antibody that is substantially free of other substances that associate with that 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. This term refers to a preparation in which the isolated protein is pure enough for analysis or at least 70% - 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, this antibody is purified.

[0077] Terms such as "specific binding" and "binds specifically" mean that two or more molecules form a complex that is measurable and selective under physiological or assay conditions. An antibody or antigen-binding protein or other molecule is said to "bind specifically" to a protein, antigen, or epitope if, under appropriately selected conditions, such binding is not substantially inhibited and at the same time non-specific binding is inhibited. Specific binding is characterized by high affinity and is selective for a compound, protein, epitope, or antigen. Non-specific binding generally has a lower affinity. For example, the binding in an IgG antibody is generally characterized by an affinity of at least about 10 -7 M or more, for example, at least about 10 -8 M or more, or at least about 10 -9 M or more, or at least about 10 -10 M or more, or at least about 10-11 M or more, or at least about 10 -12 M or more. This term is also applicable, for example, when an antigen-binding domain is specific for a particular epitope that is not retained by a number of antigens, in which case an antibody or antigen-binding protein that retains the antigen-binding domain generally does not bind to other antigens. In some embodiments, the capture reagent has a Kd of 10 -9 M, 10 -10 M, or 10 -11 M or less for its binding partner (e.g., antigen). In some embodiments, the capture reagent has a Ka of 10 9 M -1 or more for its binding partner.

[0078] An intact antibody, also known as an immunoglobulin, is typically a tetrameric glycoprotein composed of two light (L) chains, each approximately 25 kDa, and two heavy (H) chains, each approximately 50 kDa. There are two types of light chains, called lambda and kappa. Depending on the amino acid sequence of the constant domain of the heavy chain, immunoglobulins are assigned to five main classes: A, D, E, G, and M, some of which can be further divided into subclasses (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. Each light chain is composed of an N-terminal variable (V) domain (V L ) and a constant (C) domain (CL). Each heavy chain is composed of an N-terminal V domain (V H ), three or four C domains (CH), and a hinge region. The CH domain closest to V H is designated CH1. V H and V L domains consist of four regions of relatively conserved sequences, named framework regions (FR1, FR2, FR3, and FR4), which form scaffolds for three regions of hypervariable sequences (complementary determining regions, CDRs). Most of the residues involved in the specific interaction between an antibody or antigen-binding protein and an antigen are included in the CDRs. The CDRs are called CDR1, CDR2, and CDR3. Thus, the CDR components of the heavy chain are called H1, H2, and H3, while those of the light chain are called L1, L2, and L3. CDR3 is the greatest source of molecular diversity within the antibody or antigen-binding protein binding site. For example, H3 can be as short as about two amino acid residues or exceed 26 amino acids. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known in the art. For a review of antibody structure, see Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, Eds. Harlow et al., 1988. One of ordinary skill in the art will recognize each subunit structure, such as CH, V H , CL, V LIt is recognized that the CDR and / or FR structures contain active fragments. For example, the active fragment may consist of a V that binds to an antigen, H a V, L or a portion of a CDR subunit, i.e., an antigen-binding fragment, or a portion of a CH subunit that binds to and / or activates an Fc receptor and / or complement.

[0079] In addition to the fragments described herein, non-limiting examples of binding fragments included within the term "antigen-specific antibody" as used herein include (i) a Fab fragment, i.e., a monovalent fragment consisting of V, L a V, H CL and CH1 domains; (ii) an F(ab')2 fragment, i.e., a divalent fragment containing two Fab fragments linked by a disulfide bridge in the hinge region; (iii) an Fd fragment consisting of V, H and CH1 domains; (iv) an Fv fragment consisting of the V of a single arm of an antibody, L and V, H domains; (v) a dAb fragment consisting of a V, H domain; and (vi) an isolated CDR. Further, the two domains V, L and V, H of an Fv fragment are encoded by separate genes, but they may be recombinantly joined by a synthetic linker that makes a single protein chain, and their V, L and V, H domains pair to form a monovalent molecule (known as a single-chain Fv (scFv)). The most commonly used linker is a 15-residue (Gly4Ser) 3 peptide, but other linkers are also known in the art. Single-chain antibodies are also to be included within the terms "antibody or antigen-binding protein" or "antigen-binding fragment" of an antibody. An antibody may also be a polyclonal antibody, monoclonal antibody, chimeric antibody, antigen-binding fragment, Fc fragment, single-chain antibody, or any derivative thereof.

[0080] These antibodies may be obtained by those skilled in the art using conventional techniques known in the art and described herein, and this fragment is used in the same manner as intact antibodies. Antibody diversity is created by multiple germline genes encoding variable domains and various somatic events. Somatic events include recombination of variable gene segments having diversity (D) and joining (J) gene segments to create a complete V H domain, as well as recombination of variable gene segments and joining gene segments to create a complete V L domain. The recombination process itself is inaccurate and results in loss or addition of amino acids at the V(D)J junction. These diversity mechanisms occur in developing B cells prior to antigen exposure. After antigen stimulation, the antibody genes expressed in B cells undergo somatic mutation. Considering the estimated number of germline gene segments, random recombination of these segments, and random V H -V L pairing, up to 1.6 X 10 7 different antibodies can be generated (Fundamental Immunology, 3rd ed. (1993), ed. Paul, Raven Press, New York, N.Y.). Taking into account other processes contributing to antibody diversity (such as somatic mutation), it is thought that up to 1 X 10 10 different antibodies can be generated (Immunoglobulin Genes, 2nd ed. (1995), eds. Jonio et al., Academic Press, San Diego, Calif.). Since many processes are involved in the generation of antibody diversity, it is unlikely that independently derived monoclonal antibodies having the same antigen specificity will have the same amino acid sequence.

[0081] Antibodies or antigen-binding protein molecules that can specifically interact with the antigens, epitopes, or other molecules described herein can be generated by methods well known to those skilled in the art. For example, monoclonal antibodies can be produced by generating hybridomas according to known methods. The hybridomas formed in this way can then be screened using standard methods such as enzyme-linked immunosorbent assay (ELISA) and biosensor analysis to identify one or more hybridomas that produce antibodies that specifically interact with the molecule or compound of interest.

[0082] Instead of preparing monoclonal antibody-secreting hybridomas, monoclonal antibodies against polypeptides can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the polypeptides described herein, thereby isolating immunoglobulin library members that bind to the polypeptide. Techniques and commercially available kits for generating and screening phage display libraries are well known to those skilled in the art. Furthermore, examples of methods and reagents particularly suitable for use in the generation and screening of antibody or antigen-binding protein display libraries can be found in the literature. Thus, the epitopes described herein can be used to screen for other antibodies that can be used as therapeutic, diagnostic, or research tools.

[0083] Antibody-containing administrations, compositions, and kits

[0084] Antibodies containing the peptides provided herein can be used in therapeutic antibodies or antibodies used to detect or bind to different targets.

[0085] For therapeutic administration, any active form of antibody, including but not limited to scFv, Fab, and F(ab’)2 fragments, may be administered. These are merely examples and are not intended to be limiting, and any antibody form provided herein or known may be used.

[0086] In some embodiments, the antibodies used are compatible with the recipient species such that they do not result in a circulation half-life that is unacceptably short for an immune response to the MAb and also do not induce an immune response to the MAb in the subject. In some embodiments, the administered MAb exhibits some secondary functions such as binding to Fc receptors of the subject and activation of the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism.

[0087] Treatment of an individual can include administration of a therapeutically effective amount of an antibody as described herein. The antibody may be provided in a kit as described below. The antibody may be used or administered alone, or in combination or admixture with another therapeutic agent, analgesic, or diagnostic agent. When providing an antibody or fragment thereof that can bind to a target protein to a patient, the dosage of the agent administered will vary depending on factors such as the patient's age, weight, height, gender, general medical condition, previous medical history, and the like.

[0088] Suitable vehicles and their formulations and packaging are described, for example, in Remington: The Science and Practice of Pharmacy (21st ed., Troy, D., ed., Lippincott Williams & Wilkins, Baltimore, Md. (2005) Chapters 40 and 41). Additional pharmaceutical methods may be employed to control the duration of action. Sustained-release preparations can be achieved by complexing or absorbing the compound using a polymer. Another possible method for controlling the duration of action by means of a sustained-release preparation is to incorporate the compound into particles of a polymeric material such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylene vinyl acetate copolymers. Alternatively, instead of incorporating these agents into polymeric particles, it is possible to encapsulate these materials, for example, in microcapsules prepared by interfacial polymerization, such as hydroxy methyl cellulose or gelatin-microcapsules and poly(methyl methacrylate)-microcapsules, respectively, in colloidal drug delivery systems (such as liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions.

[0089] Generally, when administering a systemic dosage of an antibody, it is desirable to provide the recipient with a dosage of the antibody in the range of about 1 ng / kg to 100 ng / kg, 100 ng / kg to 500 ng / kg, 500 ng / kg to 1 μg / kg, 1 μg / kg to 100 μg / kg, 100 μg / kg to 500 μg / kg, 500 μg / kg to 1 mg / kg, 1 mg / kg to 50 mg / kg, 50 mg / kg to 100 mg / kg, 100 mg / kg to 500 mg / kg (recipient's body weight), although lower or higher dosages may be administered. A certain degree of effect may be expected at a relatively low dosage of about 1.0 mg / kg. Preferably, about 5 mg / kg is an acceptable dosage, although dosage levels up to about 50 mg / kg are also particularly preferred for therapeutic use. Alternatively, a specific amount of the antibody not based on the patient's body weight may be administered, such as an amount in the range of 1 μg to 100 μg, 1 mg to 100 mg, or 1 g to 100 g. For example, site-specific administration may be administration to a body compartment or cavity such as intra-articular, intratracheal, intraperitoneal, intracapsular, intra-cartilaginous, intracavitary, intracelial, intraperitoneal, intracerebellar, intraventricular, intracolonic, intrauterine, intragastric, intrahepatic, intramuscular, intraosseous, intrapelvic, epicardial, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, vaginal, rectal, buccal, sublingual, intranasal, or by percutaneous means.

[0090] The antibody compositions described herein can be prepared for parenteral (subcutaneous, intramuscular or intravenous) or any other administration, particularly for use in the form of a liquid solution or suspension. The formulations may also be suitable for injectable formulations. In some embodiments, the injectable formulations are sterile. In some embodiments, the injectable formulations are pyrogen-free. In some embodiments, the formulations do not contain other antibodies that bind to antigens other than the antigens described herein.

[0091] Antibodies that may contain a common light chain as provided herein can be administered as a therapeutically effective amount. An amount is said to be a "therapeutically effective amount" or an amount "effective to affect" symptom reduction if the dosage, route of administration, and dosing schedule of the agent are sufficient to affect such a response. The response to antibody administration can be measured by analysis of the affected tissue, organ, or cells of a subject, such as by imaging techniques or ex vivo analysis of tissue samples. An agent is physiologically significant if its presence results in a detectable change in the physiology of the recipient patient.

[0092] The antibodies may be formulated according to known methods to prepare pharmaceutically useful compositions, whereby these materials or their functional derivatives are combined by mixing with a pharmaceutically acceptable carrier vehicle. Treatment may be given on a single-dose schedule or the primary course of treatment consists of 1 to 10 separate administrations, followed by additional administrations at subsequent time intervals necessary to maintain and / or enhance the response (e.g., at the second administration, 1 to 4 months, and at subsequent administrations (if any) several months later as needed). Examples of suitable treatment schedules include (i) 0, 1 month, and 6 months, (ii) 0, 7 days, and 1 month, (iii) 0 and 1 month, (iv) 0 and 6 months, or other schedules sufficient to reduce the symptoms of the disease or elicit a desired response expected to reduce the severity of the disease.

[0093] Kits useful for practicing the embodiments described herein are also provided. The kit includes a first container that contains or is packaged together with the above-described antibody. The kit may also include or be packaged with another container that contains related solutions necessary or convenient for practicing the embodiment. The container may be made of glass, plastic, or foil and may be a vial, bottle, pouch, tube, bag, etc. The kit may also be provided with written information, such as procedures for practicing the embodiment, or analytical information, such as the amount of reagent contained in the first container. This container, together with the written information, may be in a separate It may be in a container device, such as a box or a bag.

[0094] Yet another aspect provided herein is a kit for detecting a protein in a biological sample. The kit comprises a container holding one or more antibodies comprising a common light chain (e.g., one of the sequences of SEQ ID NOs: 1-9 or SEQ ID NOs: 18-80 or 84), and instructions for using the antibodies for the purpose of detecting the formation of an immunological complex by binding to a target protein or antigen to form the immunological complex, and detecting the formation of the immunological complex such that the presence or absence of the immunological complex correlates with the presence or absence of the target protein (or antigen) in the sample. Examples of the container include a multi-well plate that enables simultaneous detection of target proteins in multiple samples.

[0095] In some embodiments, an antibody that binds to a target protein is provided. In some embodiments, the antibody is isolated. In some embodiments, the antibody binds specifically. In some embodiments, the antibody that binds to the target protein is properly folded. In some embodiments, the antibody that binds to the target protein is located in the cell membrane. In some embodiments, the antibody is a plurality of transmembrane proteins. In some embodiments, the protein is a seven-transmembrane protein. In some embodiments, the protein is a four-transmembrane protein. In some embodiments, the antibody binds to a target protein in the cell membrane of intact cells. In some embodiments, the antibody inhibits or neutralizes the function of the target protein. As used herein, the term "neutralize" means that the activity or function of the protein is inhibited. In some embodiments, the antibody is used as a targeting moiety for delivering another therapeutic agent to cells expressing the target protein. In some embodiments, an antibody comprising a common light chain is part of a multispecific therapy where a portion of the molecule binds to the target protein and another portion of the therapy binds to another target. In some embodiments, the other portion is a CD3-binding molecule (e.g., a CD3 antibody) or another molecule that facilitates ADC, ADCC, or CAR-T therapy. The inhibition may be complete or partial. In some embodiments, the activity or function of the target protein is inhibited, modulated, or enhanced by at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or 99%. The percent modulation may be based on the function or activity of the protein in the absence of the antibody.

[0096] In some embodiments, the antibody comprises the sequences provided herein or an antigen-binding fragment thereof. In some embodiments, the antibody comprises a heavy-chain CDR described herein or an antigen-binding fragment thereof. The heavy chain can be one or more of the heavy chains described herein. In some embodiments, the antibody comprises the light chain provided herein or an antigen-binding fragment thereof.

[0097] In some embodiments, a method for detecting the presence or absence of a target protein in a sample is provided, the method comprising contacting the sample with one or more antibodies described herein that detect binding of the target protein by the antibody. In some embodiments, detection of binding indicates the presence of the target protein or molecule. Or, if no binding to the target protein (antigen) is detected, it indicates the absence of the target protein (antigen). This detection may be performed by any known method, such as using a biosensor, ELISA, sandwich assay, flow cytometry, etc. However, in some embodiments, the method comprises detecting the presence of the protein under non-denaturing conditions. Non-denaturing conditions may be used to detect the protein of interest in its native or properly folded form.

[0098] In some embodiments of the methods provided herein, the antibody is any antibody or fragment thereof provided herein.

[0099] In some embodiments, the protein or antibody comprises a sequence as described in the following table:

Table 2

[0100] In some embodiments, the antibody is a V of any one of SEQ ID NOs: 1-9 LIt includes a protein or one or more sequences of SEQ ID NO: 18-80 or 84. In some embodiments, this protein includes a sequence that is at least, or about 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to this sequence. In some embodiments, a protein is provided that includes any one sequence of SEQ ID NO: 1-9 or SEQ ID NO: 18-80 or 84. In some embodiments, the protein includes 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions. In some embodiments, the substitution is a conservative substitution. In some embodiments, the substitution is a conservative substitution. In some embodiments, the mutation or substitution is in the framework region of the light chain. In some embodiments, the substitution is in a CDR region such as CDR1, CDR2, or CDR3. In some embodiments, the mutation or substitution is in CDR1 rather than CDR2 or CDR3. In some embodiments, the light chain includes a substitution or change in the framework region rather than in the CDR region as provided herein. In some embodiments, a light chain or protein is provided whose sequence is at least or about 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NO: 1-9, provided that That this array is a first amino acid sequence or a first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, 76 and 84; a second amino acid sequence or a second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, and 79; and a third amino acid sequence or a third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80. Thus, in some embodiments, the CDRs are not variants of the CDRs provided herein. The percent identity can be determined as provided herein or using the default parameters of BLASTP for aligning two sequences available through the website of the National Center for Biotechnology Information.

[0101] In some embodiments, the protein or antibody comprises a sequence as shown in the following table, Table 2 (different segments can be ligated together in a continuous sequence):

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

Table 17

[0102] In some embodiments, this protein or antibody comprises a sequence selected from the sequences in column FW1 of Table 2, column LCDR1 of Table 2, column FW2 of Table 2, column LCDR2 of Table 2, column FW3 of v, column LCDR3 of v, and column FW4 of Table 2. In some embodiments, the protein or antibody comprises a sequence selected from the sequences in LCDR1 of Table 2, LCDR2 of v, and LCDR3 of Table 2. As used herein, LCDR is the CDR present in the light chain of an antibody.

[0103] In some embodiments, the protein or antibody comprises a sequence set forth in Table 3. In some embodiments, the protein or antibody comprises one sequence from column CDR1 of Table 3, one sequence from column CDR2 of Table 3, and / or one sequence from column CDR3 of Table 3.

Table 18

[0104] In some embodiments, this protein comprises the sequences set forth in SEQ ID NOs: 18 to 80.

[0105] In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 19 In some embodiments, this protein or antibody comprises the LCDR2 of SEQ ID NO: 20. In some embodiments, this protein or antibody comprises the LCDR3 of SEQ ID NO: 23. In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 19, the LCDR2 of SEQ ID NO: 21, and the LCDR3 of SEQ ID NO: 23. In some embodiments, this protein comprises one, two, or each of SEQ ID NO: 19, SEQ ID NO: 21, and SEQ ID NO: 23.

[0106] In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 52. In some embodiments, this protein or antibody comprises the LCDR2 of SEQ ID NO: 54. In some embodiments, this protein or antibody comprises the LCDR3 of SEQ ID NO: 56. In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 52, the LCDR2 of SEQ ID NO: 54, and the LCDR3 of SEQ ID NO: 56. In some embodiments, this protein comprises one, two, or each of SEQ ID NO: 52, SEQ ID NO: 54, and SEQ ID NO: 56.

[0107] In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 58. In some embodiments, this protein or antibody comprises the LCDR2 of SEQ ID NO: 60. In some embodiments, this protein or antibody comprises the LCDR3 of SEQ ID NO: 61. In some embodiments, this protein or antibody comprises the LCDR1 of SEQ ID NO: 58, the LCDR2 of SEQ ID NO: 60, and the LCDR3 of SEQ ID NO: 61. In some embodiments, this protein comprises one, two, or each of SEQ ID NO: 58, SEQ ID NO: 60, and SEQ ID NO: 61.

[0108] In some embodiments, this protein or antibody comprises LCDR1 of SEQ ID NO: 63. In some embodiments, this protein or antibody comprises LCDR2 of SEQ ID NO: 64. In some embodiments, this protein or antibody comprises LCDR3 of SEQ ID NO: 65. In some embodiments, this protein or antibody comprises LCDR1 of SEQ ID NO: 63, LCDR2 of SEQ ID NO: 64, and LCDR3 of SEQ ID NO: 66. In some embodiments, this protein comprises one, two, or each of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 65.

[0109] In some embodiments, this protein or antibody comprises LCDR1 of SEQ ID NO: 66. In some embodiments, this protein or antibody comprises LCDR2 of SEQ ID NO: 67. In some embodiments, this protein or antibody comprises LCDR3 of SEQ ID NO: 68. In some embodiments, this protein or antibody comprises LCDR1 of SEQ ID NO: 66, LCDR2 of SEQ ID NO: 67, and LCDR3 of SEQ ID NO: 68. In some embodiments, this protein comprises one, two, or each of SEQ ID NO: 66, SEQ ID NO: 67, and SEQ ID NO: 68.

[0110] In some embodiments, this protein or antibody comprises a first sequence or first CDR selected from the group consisting of SEQ ID NO: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, and 76; a second sequence or second CDR selected from the group consisting of SEQ ID NO: 21, 54, 60, 64, 67, 72, 77, and 79; and a third sequence or third CDR selected from the group consisting of SEQ ID NO: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80.

[0111] In some embodiments, this protein or antibody comprises a first sequence or a first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, and 70; a second sequence or a second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, and 67; and a third sequence or a third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 4 8, 56, 61, 65, and 68.

[0112] In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 21, and 23. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 27, and 23. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 18, 21, and 23. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 21, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 21, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 49, 21, and 23. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 50, 21, and 23. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 51, 21, and 47.

[0113] In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 52, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 54, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 19, 54, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 62, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 49, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 57, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 51, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 58, 60, and 61. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 58, 60, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 58, 60, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 62, 60, and 61. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 49, 60, and 61. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 57, 60, and 61. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NOs: 51, 60, and 61.

[0114] In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 63, 64, and 65. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 63, 64, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 63, 64, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 49, 64, and 65. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 57, 64, and 65. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 51, 64, and 65.

[0115] In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 66, 67, and 68. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 66, 67, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 66, 67, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 69, 67, and 68. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 49, 67, and 68. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 57, 67, and 68. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 51, 67, and 68.

[0116] In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 70, 21, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 70, 54, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 19, 21, and 47. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 52, 21, and 56. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 70, 54, and 48. In some embodiments, this protein or antibody comprises the protein sequences of SEQ ID NO: 70, 21, and 56.

[0117] In some embodiments, an antibody or antibody V L chain is provided, wherein this antibody or antibody V L chain comprises a first CDR, a second CDR, and a third CDR. In some embodiments, this antibody or antibody V L chain comprises a first CDR comprising SEQ ID NO: 19, a second CDR comprising SEQ ID NO: 21, and a third CDR comprising SEQ ID NO: 23. In some embodiments, this antibody or antibody V L chain comprises a first CDR comprising SEQ ID NO: 19, a second CDR comprising SEQ ID NO: 27, and a third CDR comprising SEQ ID NO: 23. In some embodiments, this antibody or antibody V L chain comprises a first CDR comprising SEQ ID NO: 18, a second CDR comprising SEQ ID NO: 21, and a third CDR comprising SEQ ID NO: 23. In some embodiments, this antibody or antibody V L chain comprises a first CDR comprising SEQ ID NO: 19, a second CDR comprising SEQ ID NO: 21, and a third CDR comprising SEQ ID NO: 47. In some embodiments, this antibody or antibody V L chain comprises a first CDR comprising SEQ ID NO: 19, a second CDR comprising SEQ ID NO: 21, and a third CDR comprising SEQ ID NO: 48. In some embodiments, this antibody or antibody V LThe heavy chain comprises a first CDR containing SEQ ID NO: 49, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 23. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 50, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 23. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 51, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 47.

[0118] In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 52, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 19, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 47. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 19, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 48. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 62, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 49, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 57, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L comprises a first CDR containing SEQ ID NO: 51, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56.

[0119] In some embodiments, this antibody or antibody heavy chain LThe heavy chain comprises a first CDR containing SEQ ID NO: 58, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 61. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 58, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 47. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 58, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 48. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 62, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 61. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 49, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 61. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 57, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 61. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 51, a second CDR containing SEQ ID NO: 60, and a third CDR containing SEQ ID NO: 61.

[0120] In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 63, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 65. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 63, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 47. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 63, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 48. In some embodiments, this antibody or antibody heavy chain LThe heavy chain comprises a first CDR containing SEQ ID NO: 49, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 65. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 57, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 65. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 51, a second CDR containing SEQ ID NO: 64, and a third CDR containing SEQ ID NO: 65.

[0121] In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 66, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 68. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 66, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 47. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 66, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 48. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 69, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 68. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 9, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 68. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 57, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 68. In some embodiments, this antibody or antibody heavy chain L The heavy chain comprises a first CDR containing SEQ ID NO: 51, a second CDR containing SEQ ID NO: 67, and a third CDR containing SEQ ID NO: 68.

[0122] In some embodiments, this antibody or antibody heavy chain LThe heavy chain comprises a first CDR containing SEQ ID NO: 70, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L chain comprises a first CDR containing SEQ ID NO: 70, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L chain comprises a first CDR containing SEQ ID NO: 19, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 47. In some embodiments, this antibody or antibody heavy chain L chain comprises a first CDR containing SEQ ID NO: 52, a second CDR containing SEQ ID NO: 21, and a third CDR containing SEQ ID NO: 56. In some embodiments, this antibody or antibody heavy chain L chain comprises a first CDR containing SEQ ID NO: 70, a second CDR containing SEQ ID NO: 54, and a third CDR containing SEQ ID NO: 48.

[0123] In some embodiments, this protein comprises a first amino acid sequence or first CDR containing the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR containing the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR containing the sequence of SEQ ID NO: 23.

[0124] In some embodiments, this protein comprises a first amino acid sequence or first CDR containing the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR containing the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR containing the sequence of SEQ ID NO: 47.

[0125] In some embodiments, this protein comprises a first amino acid sequence or first CDR containing the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR containing the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR containing the sequence of SEQ ID NO: 48.

[0126] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0127] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0128] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0129] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0130] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0131] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0132] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0133] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0134] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0135] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0136] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0137] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0138] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0139] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0140] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0141] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0142] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0143] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0144] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0145] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0146] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0147] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0148] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0149] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0150] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0151] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0152] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0153] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0154] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0155] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0156] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0157] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0158] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0159] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0160] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0161] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0162] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0163] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0164] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0165] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0166] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0167] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0168] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0169] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0170] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0171] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0172] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 80.

[0173] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 23.

[0174] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0175] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0176] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0177] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0178] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0179] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0180] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0181] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0182] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0183] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0184] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0185] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0186] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0187] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0188] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0189] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0190] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0191] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0192] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0193] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0194] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0195] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0196] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0197] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0198] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0199] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0200] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0201] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0202] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 19; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0203] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0204] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0205] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0206] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0207] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0208] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0209] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0210] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0211] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0212] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0213] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0214] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0215] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0216] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0217] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0218] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0219] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0220] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0221] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0222] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0223] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0224] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0225] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0226] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0227] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0228] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0229] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0230] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0231] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0232] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0233] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0234] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0235] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0236] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0237] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0238] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0239] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0240] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0241] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0242] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0243] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0244] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0245] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0246] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0247] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0248] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0249] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0250] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0251] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0252] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0253] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0254] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0255] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0256] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0257] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0258] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0259] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0260] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0261] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0262] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0263] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0264] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0265] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0266] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0267] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0268] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0269] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0270] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0271] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0272] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 80.

[0273] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 23.

[0274] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0275] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0276] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0277] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0278] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0279] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0280] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0281] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0282] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 49; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 80.

[0283] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 23.

[0284] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0285] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0286] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0287] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0288] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0289] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0290] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0291] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0292] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0293] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0294] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0295] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0296] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0297] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0298] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0299] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0300] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0301] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0302] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0303] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0304] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0305] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0306] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0307] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0308] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0309] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0310] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0311] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0312] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0313] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0314] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0315] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0316] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0317] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0318] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0319] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0320] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0321] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0322] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0323] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0324] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0325] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0326] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0327] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0328] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0329] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0330] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0331] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0332] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0333] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0334] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0335] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0336] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0337] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0338] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0339] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0340] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0341] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0342] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0343] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0344] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0345] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0346] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0347] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0348] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0349] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0350] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0351] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0352] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0353] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0354] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0355] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0356] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0357] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0358] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0359] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0360] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0361] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0362] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 50; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0363] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0364] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0365] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0366] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0367] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0368] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0369] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0370] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0371] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0372] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0373] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0374] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0375] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0376] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0377] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0378] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0379] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0380] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0381] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0382] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0383] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0384] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0385] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0386] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0387] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0388] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0389] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0390] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0391] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0392] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0393] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0394] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0395] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0396] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0397] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0398] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0399] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0400] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0401] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0402] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0403] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0404] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0405] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0406] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0407] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0408] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0409] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0410] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0411] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0412] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0413] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0414] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0415] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0416] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0417] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0418] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0419] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0420] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0421] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0422] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0423] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0424] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0425] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0426] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0427] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0428] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0429] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0430] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0431] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0432] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0433] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0434] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0435] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0436] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0437] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0438] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0439] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0440] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0441] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0442] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 51; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0443] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0444] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0445] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0446] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0447] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0448] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0449] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0450] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0451] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0452] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0453] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0454] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0455] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0456] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0457] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0458] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0459] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0460] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0461] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0462] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0463] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0464] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0465] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0466] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0467] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0468] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0469] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0470] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0471] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0472] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0473] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0474] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0475] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0476] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0477] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0478] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0479] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0480] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0481] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0482] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0483] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0484] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0485] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0486] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0487] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0488] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0489] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0490] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0491] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0492] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0493] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0494] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0495] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0496] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0497] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0498] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0499] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0500] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0501] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0502] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0503] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0504] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0505] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0506] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0507] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0508] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0509] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0510] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0511] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0512] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0513] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0514] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0515] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0516] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0517] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0518] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0519] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0520] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0521] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0522] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 52; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 80.

[0523] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 23.

[0524] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0525] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0526] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0527] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0528] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0529] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0530] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0531] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0532] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0533] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0534] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0535] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0536] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0537] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0538] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0539] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0540] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0541] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0542] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0543] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0544] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0545] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0546] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0547] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0548] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0549] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0550] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0551] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0552] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0553] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0554] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0555] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0556] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0557] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0558] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0559] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0560] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0561] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0562] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0563] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0564] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0565] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0566] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0567] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0568] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0569] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0570] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0571] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0572] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0573] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0574] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0575] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0576] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0577] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0578] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0579] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0580] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0581] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0582] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0583] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0584] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0585] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0586] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0587] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0588] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0589] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0590] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0591] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0592] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0593] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0594] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0595] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0596] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0597] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0598] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0599] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0600] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0601] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0602] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 57; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 80.

[0603] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 23.

[0604] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0605] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0606] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0607] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0608] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0609] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0610] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0611] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0612] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0613] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0614] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0615] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0616] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0617] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0618] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0619] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0620] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0621] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0622] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0623] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0624] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0625] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0626] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0627] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0628] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0629] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0630] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0631] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0632] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0633] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0634] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0635] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0636] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0637] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0638] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0639] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0640] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 73.

[0641] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 78.

[0642] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0643] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0644] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0645] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0646] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0647] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0648] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0649] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0650] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0651] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0652] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0653] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0654] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0655] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0656] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0657] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0658] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0659] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0660] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0661] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0662] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0663] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0664] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0665] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0666] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0667] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0668] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0669] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0670] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0671] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0672] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0673] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0674] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0675] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0676] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0677] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0678] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0679] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0680] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0681] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0682] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 58; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0683] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0684] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 47.

[0685] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 48.

[0686] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 56.

[0687] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 61.

[0688] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 65.

[0689] In some embodiments, this protein comprises a first amino acid sequence or first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or third CDR comprising the sequence of SEQ ID NO: 68.

[0690] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0691] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0692] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0693] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0694] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0695] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0696] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0697] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0698] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0699] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0700] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0701] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0702] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0703] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0704] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0705] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0706] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0707] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0708] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0709] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0710] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0711] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0712] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 60; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0713] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0714] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0715] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0716] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0717] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0718] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0719] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0720] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0721] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0722] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 64; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0723] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0724] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0725] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0726] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0727] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0728] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0729] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0730] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0731] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0732] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 67; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0733] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0734] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0735] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0736] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0737] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0738] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0739] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0740] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0741] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0742] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 72; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0743] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0744] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0745] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0746] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0747] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0748] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0749] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0750] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0751] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0752] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 77; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0753] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0754] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0755] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0756] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0757] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0758] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0759] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0760] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0761] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0762] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 62; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 79; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0763] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0764] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0765] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0766] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0767] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 61.

[0768] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 65.

[0769] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 68.

[0770] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 73.

[0771] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 78.

[0772] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 21; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 80.

[0773] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 23.

[0774] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 47.

[0775] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 48.

[0776] In some embodiments, this protein comprises a first amino acid sequence or a first CDR comprising the sequence of SEQ ID NO: 63; a second amino acid sequence or a second CDR comprising the sequence of SEQ ID NO: 54; and a third amino acid sequence or a third CDR comprising the sequence of SEQ ID NO: 56.

[0777] In some embodiments, this protein comprises a first amino acid sequence or a first CDR compris...

Claims

1. A protein comprising a first amino acid sequence or a first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, 76, and 84, or any variant of the foregoing; a second amino acid sequence or a second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, and 79, or any variant of the foregoing; and a third amino acid sequence or a third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80, or any variant of the foregoing.

2. 2. The protein of claim 1, wherein the selected first sequence or the selected first CDR comprises a sequence selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, and 70; the second sequence or the second CDR comprises a sequence selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, and 67; and the third sequence or the third CDR comprises a sequence selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, and 68.

3. 2. The protein of claim 1, comprising a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third sequence or third CDR comprising the sequence of SEQ ID NO:

23.

4. 2. The protein of claim 1, wherein the protein comprises: a first sequence or first CDR comprising the sequence of SEQ ID NO:52; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:58; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:61; or a first sequence or first CDR comprising the sequence of SEQ ID NO:63; a second sequence or second CDR comprising the sequence of SEQ ID NO:64; and a third sequence or third CDR comprising the sequence of SEQ ID NO:65; or a first sequence or first CDR comprising the sequence of SEQ ID NO:66; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:68; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 27; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 23; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 18; a second sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 23; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 47; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 48; or A first sequence or first CDR comprising the sequence of SEQ ID NO:49; a second sequence or second CDR comprising the sequence of SEQ ID NO:21; and a third sequence or second CDR comprising the sequence of SEQ ID NO:

23. CDR of 3; or a first sequence or first CDR comprising the sequence of SEQ ID NO:50; a second sequence or second CDR comprising the sequence of SEQ ID NO:21; and a third sequence or third CDR comprising the sequence of SEQ ID NO:47; or a first sequence or first CDR comprising the sequence of SEQ ID NO:52; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 47; or a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 54; and a third sequence or third CDR comprising the sequence of SEQ ID NO: 48; or a first sequence or first CDR comprising the sequence of SEQ ID NO:62; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:49; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:57; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:51; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:58; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:47; or a first sequence or first CDR comprising the sequence of SEQ ID NO:58; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:48; or a first sequence or first CDR comprising the sequence of SEQ ID NO:62; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:61; or a first sequence or first CDR comprising the sequence of SEQ ID NO:49; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:61; or a first sequence or first CDR comprising the sequence of SEQ ID NO:57; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:61; or a first sequence or first CDR comprising the sequence of SEQ ID NO:51; a second sequence or second CDR comprising the sequence of SEQ ID NO:60; and a third sequence or third CDR comprising the sequence of SEQ ID NO:61; or a first sequence or first CDR comprising the sequence of SEQ ID NO:63; a second sequence or second CDR comprising the sequence of SEQ ID NO:64; and a third sequence or third CDR comprising the sequence of SEQ ID NO:65; or a first sequence or first CDR comprising the sequence of SEQ ID NO:63; a second sequence or second CDR comprising the sequence of SEQ ID NO:64; and a third sequence or third CDR comprising the sequence of SEQ ID NO:47; or A first sequence or a first CDR comprising the sequence of SEQ ID NO:63; comprising the sequence of SEQ ID NO:64 a second sequence or second CDR; and a third sequence or third CDR comprising the sequence of SEQ ID NO:48; or a first sequence or first CDR comprising the sequence of SEQ ID NO:49; a second sequence or second CDR comprising the sequence of SEQ ID NO:64; and a third sequence or third CDR comprising the sequence of SEQ ID NO:65; or a first sequence or first CDR comprising the sequence of SEQ ID NO:57; a second sequence or second CDR comprising the sequence of SEQ ID NO:64; and a third sequence or third CDR comprising the sequence of SEQ ID NO:65; or a first sequence or first CDR comprising the sequence of SEQ ID NO:66; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:68; or a first sequence or first CDR comprising the sequence of SEQ ID NO:66; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:47; or a first sequence or first CDR comprising the sequence of SEQ ID NO:66; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:48; or a first sequence or first CDR comprising the sequence of SEQ ID NO:69; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:68; or a first sequence or first CDR comprising the sequence of SEQ ID NO:57; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:68; or a first sequence or first CDR comprising the sequence of SEQ ID NO:51; a second sequence or second CDR comprising the sequence of SEQ ID NO:67; and a third sequence or third CDR comprising the sequence of SEQ ID NO:68; or a first sequence or first CDR comprising the sequence of SEQ ID NO:70; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:52; a second sequence or second CDR comprising the sequence of SEQ ID NO:21; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or a first sequence or first CDR comprising the sequence of SEQ ID NO:70; a second sequence or second CDR comprising the sequence of SEQ ID NO:54; and a third sequence or third CDR comprising the sequence of SEQ ID NO:48; or a first sequence or first CDR comprising the sequence of SEQ ID NO:70; a second sequence or second CDR comprising the sequence of SEQ ID NO:21; and a third sequence or third CDR comprising the sequence of SEQ ID NO:56; or any of the above-mentioned variants.

5. 2. The protein of claim 1, wherein the protein comprises a sequence that is at least or about 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2 (F10h), SEQ ID NO:1 (F10), SEQ ID NO:3 (B9), SEQ ID NO:4 (B9h), SEQ ID NO:5 (N6-G3), SEQ ID NO:6 (N6-C5), SEQ ID NO:7 (N6-F11), SEQ ID NO:8 (N5-B4), or SEQ ID NO:9 (N5-B7), or a variant of any of the foregoing.

6. The protein according to any one of claims 1 to 5, wherein the protein is an antibody.

7. The protein is V Ｌ Peptide or V Ｌ The method according to any one of claims 1 to 5, Proteins listed.

8. The protein further comprises V Ｈ The protein of claim 7 comprising a chain.

9. A polypeptide comprising the protein according to any one of claims 1 to 5 and a second peptide.

10. The second peptide comprises a first V Ｈ The polypeptide of claim 9 which is a peptide.

11. The first V Ｈ 11. The polypeptide of claim 10, wherein the peptide comprises the sequence of 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, or SEQ ID NO:17, or a variant of any of the foregoing.

12. The polypeptide of claim 9 , wherein the polypeptide is an antibody.

13. The polypeptide of claim 12, wherein the antibody is an scFv antibody.

14. The polypeptide of claim 9 , wherein the polypeptide comprises a sequence that is a chicken-derived protein.

15. The polypeptide of claim 9 , further comprising a third peptide.

16. The polypeptide of claim 15 , wherein the second and third peptides comprise different sequences.

17. The third peptide comprises a second V Ｈ The polypeptide of claim 15 which is a peptide.

18. The first V Ｈ A peptide and the second V Ｈ 18. The polypeptide of claim 17, wherein the peptides contain the same sequence or bind to the same target or antigen.

19. The first V Ｈ A peptide and the second V Ｈ 18. The polypeptide of claim 17, wherein the peptides comprise different sequences or bind to different targets or antigens.

20. The first and second V Ｈ 18. The polypeptide of claim 17, wherein the peptides bind to different targets or to the same target.

21. The first and second V Ｈ 18. The polypeptide of claim 17, wherein the peptides bind to the same epitope or to different epitopes.

22. 10. The polypeptide of any one of the preceding claims, wherein the polypeptide comprises a sequence selected from 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, or SEQ ID NO:17, or a variant of any of the foregoing.

23. 2. A polypeptide according to any preceding claim, wherein the polypeptide comprises a linker.

24. The polypeptide of claim 23 , wherein the linker is a peptide linker.

25. The linker is a linker that links the protein according to any one of claims 1 to 5 to the second peptide.

25. The polypeptide of claim 23 or 24, which is linked to a

26. An antibody comprising the protein according to any one of claims 1 to 5.

27. 27. The antibody of claim 26, wherein the antibody is humanized.

28. A protein according to any one of claims 1 to 5 and one or more V Ｈ A peptide-containing multispecific antibody.

29. The antibody is a first V Ｈ The peptide and the second V Ｈ 29. The multispecific antibody of claim 28 comprising a peptide.

30. The first V Ｈ A peptide and the second V Ｈ 30. The multispecific antibody of claim 29, wherein the peptides bind to different targets or to the same target.

31. The first V Ｈ A peptide and the second V Ｈ The peptide is the same V Ｌ is linked or linked to a peptide, Ｌ The multispecific antibody of claim 29, wherein the peptide comprises a protein according to any one of claims 1 to 5.

32. An antibody comprising LCDR1 of SEQ ID NO: 19, or a variant thereof.

33. An antibody comprising an LCDR2 of SEQ ID NO: 21, or a variant thereof.

34. An antibody comprising an LCDR3 of SEQ ID NO: 23, or a variant thereof.

35. An antibody comprising an LCDR1 of SEQ ID NO: 19, an LCDR2 of SEQ ID NO: 21, an LCDR3 of SEQ ID NO: 23, or any variant thereof.

36. A protein or antibody comprising a peptide comprising a sequence set forth in SEQ ID NO: 18 to 80 or 84.

37. A protein or antibody comprising a sequence set forth in Table 2 or Table 3.

38. 38. The protein or antibody of claim 36 or 37, wherein the protein or antibody comprises one, two or each of a peptide comprising the sequence of SEQ ID NO:19, SEQ ID NO:21 or SEQ ID NO:

23.

39. 39. A protein or antibody according to any one of claims 36 to 38, comprising the peptide sequences of SEQ ID NO:19 and SEQ ID NO:21; the peptide sequences of SEQ ID NO:19 and SEQ ID NO:23; the peptide sequences of SEQ ID NO:21 and SEQ ID NO:23, or the peptide sequences of SEQ ID NO:19, SEQ ID NO:21 and SEQ ID NO:

23.

40. A protein having the formula: FW1-CDR1-FW2-CDR2-FW3-CDR3-FW4, wherein: FW1 is a peptide having a formula or sequence set forth in SEQ ID NO: 18, 25, 31, 36, 38 or 46, or a variant of any of the foregoing; CDR1 is a peptide having a formula or sequence set forth in any one of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, 76, or 84, or a variant of any of the foregoing; FW2 is a polypeptide having a formula or sequence set forth in SEQ ID NO: 20, 26, 30, 32, 35, or 53. or a variant of any of the foregoing; CDR2 is a peptide having a formula or sequence set forth in any one of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, or 79, or a variant of any of the foregoing; FW3 is a peptide having a formula or sequence set forth in SEQ ID NO: 22, 27, 33, 37, 39, 41, 42, 44, 45, 55, or 59, or a variant of any of the foregoing; CDR3 is a peptide having a formula or sequence set forth in any one of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, or 80, or a variant of any of the foregoing; and FW4 is a peptide having the formula or sequence set forth in SEQ ID NO: 24, 29, 34, 40 or 43, or a variant of any of the foregoing.

41. The protein and V of claim 40 Ｈ A polypeptide comprising a domain.

42. The protein and V of claim 40 Ｈ 42. The polypeptide of claim 41, wherein the domains are linked together via a linker.

43. 43. The polypeptide of claim 41 or 42, wherein the polypeptide is an antibody.

44. A nucleic acid molecule encoding a protein, polypeptide or antibody according to any one of claims 1 to 43.

45. A vector comprising the nucleic acid molecule of claim 44.

46. 46. ​​A cell comprising a nucleic acid, comprising the nucleic acid molecule of claim 44 or the vector of claim 45.

47. A pharmaceutical composition comprising a protein, polypeptide or antibody according to any one of claims 1 to 43, or a nucleic acid molecule encoding them.

48. 44. A method for delivering a protein, polypeptide or antibody according to any one of claims 1 to 43 to a subject, the method comprising administering to the subject the protein, polypeptide or antibody according to any one of claims 1 to 43, or a nucleic acid molecule encoding it.

49. 44. A method of treating a disease in a subject using a protein, polypeptide or antibody according to any one of claims 1 to 43, comprising administering to the subject a protein, polypeptide or antibody according to any one of claims 1 to 43, or a nucleic acid molecule encoding the same.

50. 1. A method for preparing an antibody, comprising culturing a host cell comprising a nucleotide sequence encoding a light chain and a heavy chain derived from a chicken that binds to a specific antigen, and expressing the antibody comprising the light chain and the heavy chain derived from a chicken that binds to the specific antigen.

51. The nucleotide sequence comprises a first amino acid sequence or a first CDR selected from the group consisting of SEQ ID NOs: 19, 49, 50, 51, 52, 57, 58, 62, 63, 66, 69, 70, 71, 74, 75, 76, and 84, or a variant of any of the foregoing; a second amino acid sequence or a second CDR selected from the group consisting of SEQ ID NOs: 21, 54, 60, 64, 67, 72, 77, and 79, or a variant of any of the foregoing; and 51. The method of claim 50, encoding a light chain comprising a protein comprising a third amino acid sequence or a third CDR selected from the group consisting of SEQ ID NOs: 23, 47, 48, 56, 61, 65, 68, 73, 78, and 80, or a variant of any of the foregoing.

52. 51. The method of claim 50, wherein the light chain protein comprises a first sequence or first CDR comprising the sequence of SEQ ID NO: 19; a second sequence or second CDR comprising the sequence of SEQ ID NO: 21; and a third sequence or third CDR comprising the sequence of SEQ ID NO:

23.

53. 51. The method of claim 50, wherein the nucleotide sequence encodes a light chain protein that is at least 90% identical to a protein having the sequence of SEQ ID NO:2 (F10h), SEQ ID NO:1 (F10), SEQ ID NO:3 (B9), SEQ ID NO:4 (B9h), SEQ ID NO:5 (N6-G3), SEQ ID NO:6 (N6-C5), SEQ ID NO:7 (N6-F11), SEQ ID NO:8 (N5-B4), or SEQ ID NO:9 (N5-B7).

54. 51. The method of claim 50, wherein the nucleotide sequence encodes a protein having a sequence of SEQ ID NO:2 (F10h), SEQ ID NO:1 (F10), SEQ ID NO:3 (B9), SEQ ID NO:4 (B9h), SEQ ID NO:5 (N6-G3), SEQ ID NO:6 (N6-C5), SEQ ID NO:7 (N6-F11), SEQ ID NO:8 (N5-B4), or SEQ ID NO:9 (N5-B7), or a light chain protein comprising a variant of any of the foregoing.

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