US20170183412A1 - Human Antigen Binding Proteins That Bind To a Complex Comprising beta-Klotho and an FGF Receptor - Google Patents

Abstract

The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

Description

• This application is a division of U.S. application Ser. No. 13/487,061 (filed Jun. 1, 2012), which claims the benefit of U.S. Provisional Application Nos. 61/493,933 (filed Jun. 6, 2011), 61/501,133 (filed Jun. 24, 2011), and 61/537,998 (filed Sep. 22, 2011), the contents of each of which are hereby incorporated in their entirety.
SEQUENCE LISTING
• The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Aug. 10, 2016, is named A-1650-US—NP_SEQ_LIST_2094_08 10 2016. txt and is 1,661 KB in size.
FIELD OF THE INVENTION
• The present disclosure relates to nucleic acid molecules encoding antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including antigen binding proteins that induce FGF21-like signaling, as well as pharmaceutical compositions comprising antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including antigen binding proteins that induce FGF21-like signaling, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions. Diagnostic methods using the antigen binding proteins are also provided.
BACKGROUND
• Fibroblast Growth Factor 21 (FGF21) is a secreted polypeptide that belongs to a subfamily of Fibroblast Growth Factors (FGFs) that includes FGF19, FGF21, and FGF23 (Itoh et al., (2004) Trend Genet. 20:563-69). FGF21 is an atypical FGF in that it is heparin independent and functions as a hormone in the regulation of glucose, lipid, and energy metabolism.
• It is highly expressed in liver and pancreas and is the only member of the FGF family to be primarily expressed in liver. Transgenic mice overexpressing FGF21 exhibit metabolic phenotypes of slow growth rate, low plasma glucose and triglyceride levels, and an absence of age-associated type 2 diabetes, islet hyperplasia, and obesity. Pharmacological administration of recombinant FGF21 protein in rodent and primate models results in normalized levels of plasma glucose, reduced triglyceride and cholesterol levels, and improved glucose tolerance and insulin sensitivity. In addition, FGF21 reduces body weight and body fat by increasing energy expenditure, physical activity, and metabolic rate. Experimental research provides support for the pharmacological administration of FGF21 for the treatment of type 2 diabetes, obesity, dyslipidemia, and other metabolic conditions or disorders in humans.
• FGF21 is a liver derived endocrine hormone that stimulates glucose uptake in adipocytes and lipid homeostasis through the activation of its receptor. Interestingly, in addition to the canonical FGF receptor, the FGF21 receptor also comprises the membrane associated β-Klotho as an essential cofactor. Activation of the FGF21 receptor leads to multiple effects on a variety of metabolic parameters.
• In mammals, FGFs mediate their action via a set of four FGF receptors, FGFR1-4, that in turn are expressed in multiple spliced variants, e.g., FGFR1c, FGFR2c, FGFR3c and FGFR4. Each FGF receptor contains an intracellular tyrosine kinase domain that is activated upon ligand binding, leading to downstream signaling pathways involving MAPKs (Erk1/2), RAF1, AKT1 and STATs. (Kharitonenkov et al., (2008) BioDrugs 22:37-44). Several reports suggested that the “c”-reporter splice variants of FGFR1-3 exhibit specific affinity to β-Klotho and could act as endogenous receptor for FGF21 (Kurosu et al., (2007) 1 Biol. Chem. 282:26687-95); Ogawa et al., (2007) Proc. Natl. Acad. Sci. USA 104:7432-37); Kharitonenkov et al., (2008) J. Cell Physiol. 215:1-7). In the liver, which abundantly expresses both β-Klotho and FGFR4, FGF21 does not induce phosphorylation of MAPK albeit the strong binding of FGF21 to the β-Klotho-FGFR4 complex. In 3T3-L1 cells and white adipose tissue, FGFR1 is by far the most abundant receptor, and it is therefore most likely that FGF21's main functional receptors in this tissue are the β-Klotho/FGFR1c complexes.
• The present disclosure provides a human (or humanized) antigen binding protein, such as a monoclonal antibody, that induces FGF21-like signaling, e.g., an agonistic antibody that mimics the function of FGF21. Such an antibody is a molecule with FGF21-like activity and selectivity but with added therapeutically desirable characteristics typical for an antibody such as protein stability, lack of immunogenicity, ease of production and long half-life in vivo.
SUMMARY
• The instant disclosure provides antigen binding proteins that bind a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including antigen binding proteins that induce FGF21-like signaling, as well as pharmaceutical compositions comprising antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including antigen binding proteins that induce FGF21-like signaling. In another aspect, also provided are expression vectors and host cells transformed or transfected with the expression vectors that comprise the aforementioned isolated nucleic acid molecules that encode the antigen binding proteins disclosed herein. Representative heavy and light chains are provided in Tables 1A and 1B; representative variable region heavy chain and light chain sequences are provided in Tables 2A and 2B; coding sequences for the variable region of the heavy and light chains are provided in Tables 2C and 2D; Tables 3A and 3B provide CDR regions of the disclosed variable heavy and light chains, and Tables 3C and 3D provide coding sequences for the disclosed CDRs.
• In another aspect, also provided are methods of preparing antigen binding proteins that specifically or selectively bind a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and comprise the step of preparing the antigen binding protein from a host cell that secretes the antigen binding protein.
• Other embodiments provide a method of preventing or treating a condition in a subject in need of such treatment comprising administering a therapeutically effective amount of a pharmaceutical composition provided herein to a subject, wherein the condition is treatable by lowering blood glucose, insulin or serum lipid levels. In embodiments, the condition is type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease or metabolic syndrome.
• These and other aspects are described in greater detail herein. Each of the aspects provided can encompass various embodiments provided herein. It is therefore anticipated that each of the embodiments involving one element or combinations of elements can be included in each aspect described, and all such combinations of the above aspects and embodiments are expressly considered. Other features, objects, and advantages of the disclosed antigen binding proteins and associated methods and compositions are apparent in the detailed description that follows.
BRIEF DESCRIPTION OF THE FIGURES
• FIG. 1a-1b is an alignment showing the sequence homology between human FGFR1c (GenBank Accession No P11362; SEQ ID NO: 4) and murine FGFR1c (GenBank Accession No NP 034336; SEQ ID NO: 1832); various features are highlighted, including the signal peptide, transmembrane sequence, heparin binding region, and a consensus sequence (SEQ ID NO: 1833) is provided.
• FIG. 2a-2c is an alignment showing the sequence homology between human β-Klotho (GenBank Accession No NP_783864; SEQ ID NO: 7) and murine β-Klotho (GenBank Accession No NP_112457; SEQ ID NO: 10); various features are highlighted, including the transmembrane sequence and two glycosyl hydrolase domains, and a consensus sequence (SEQ ID NO: 1834) is provided.
• FIG. 3 is a plot showing the representative data from Luciferase reporter activity screens of the antibodies disclosed herein with FGF21 and a reference antibody 16H7.1 as positive controls (insert); these hybridomas were generated by immunization with cell-bound receptor of 293T transfectants expressing full length human β-Klotho and an N-terminal truncated form of human FGFR1c encompassing amino acid residue #141 to #822 polypeptide of SEQ ID NO:4. X- and Y-axis in the plot are % FGF21 activity from two independent assays (n=1 and n=2) of the same set of hybridoma samples (gray circles) showing the consistency of the assays; several hybridoma samples were also included as negative controls (black circles);
• FIG. 4 shows a schematic representation of the chimeras constructed in relation to present invention.
• FIG. 5 shows the ability of the antigen binding proteins, as well as human FGF21, to activate chimeras in L6 cells.
• FIGS. 6a-e show the amino acid alignment of heavy and light chains of the antibodies compared to the corresponding germline V-gene sequence.
DETAILED DESCRIPTION
• The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.
• Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
• Generally, nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well known and commonly used in the art. The methods and techniques of the present application are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 3^rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2001) and subsequent editions, Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates (1992), and Harlow & Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1988), which are incorporated herein by reference. Enzymatic reactions and purification techniques are performed according to manufacturer's specifications, as commonly accomplished in the art or as described herein. The terminology used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well known and commonly used in the art. Standard techniques can be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.
• It should be understood that the instant disclosure is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such can vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure.
• Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean±5%, e.g., 1%, 2%, 3%, or 4%.
I. Definitions
• As used herein, the terms “a” and “an” mean “one or more” unless specifically stated otherwise.
• As used herein, an “antigen binding protein” is a protein comprising a portion that binds to an antigen or target and, optionally, a scaffold or framework portion that allows the antigen binding portion to adopt a conformation that promotes binding of the antigen binding protein to the antigen. Examples of antigen binding proteins include a human antibody, a humanized antibody; a chimeric antibody; a recombinant antibody; a single chain antibody; a diabody; a triabody; a tetrabody; a Fab fragment; a F(ab′)₂ fragment; an IgD antibody; an IgE antibody; an IgM antibody; an IgG1 antibody; an IgG2 antibody; an IgG3 antibody; or an IgG4 antibody, and fragments thereof. The antigen binding protein can comprise, for example, an alternative protein scaffold or artificial scaffold with grafted CDRs or CDR derivatives. Such scaffolds include, but are not limited to, antibody-derived scaffolds comprising mutations introduced to, for example, stabilize the three-dimensional structure of the antigen binding protein as well as wholly synthetic scaffolds comprising, for example, a biocompatible polymer. See, e.g., Korndorfer et al., (2003) Proteins: Structure, Function, and Bioinformatics, 53(1):121-129; Roque et al., (2004) Biotechnol. Prog. 20:639-654. In addition, peptide antibody mimetics (“PAMs”) can be used, as well as scaffolds based on antibody mimetics utilizing fibronectin components as a scaffold.
• An antigen binding protein can have, for example, the structure of a naturally occurring immunoglobulin. An “immunoglobulin” is a tetrameric molecule. In a naturally occurring immunoglobulin, each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxy-terminal portion of each chain defines a constant region primarily responsible for effector function. Human light chains are classified as kappa and lambda light chains. Heavy chains are classified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a “J” region of about 12 or more amino acids, with the heavy chain also including a “D” region of about 10 more amino acids. See generally, Fundamental Immunology 2^nd ed. Ch. 7 (Paul, W., ed., Raven Press, N.Y. (1989)), incorporated by reference in its entirety for all purposes. The variable regions of each light/heavy chain pair form the antibody binding site such that an intact immunoglobulin has two binding sites.
• Naturally occurring immunoglobulin chains exhibit the same general structure of relatively conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CDRs. From N-terminus to C-terminus, both light and heavy chains comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain can be done in accordance with the definitions of Kabat et al., (1991) “Sequences of Proteins of Immunological Interest”, 5^th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242. Although presented herein using the Kabat nomenclature system, as desired, the CDRs disclosed herein can also be redefined according an alternative nomenclature scheme, such as that of Chothia (see Chothia & Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670).
• In the context of the instant disclosure an antigen binding protein is said to “specifically bind” or “selectively bind” its target antigen when the dissociation constant (K_D) is ≦10⁻⁸ M. The antibody specifically binds antigen with “high affinity” when the K_D is ≦5×10⁻⁹ M, and with “very high affinity” when the K_D is ≦5×10⁻¹⁰ M. In one embodiment, the antibodies will bind to a complex comprising β-Klotho and an FGFR, including a complex comprising both human FGFR1c and human β-Klotho, with a K_D of between about 10⁻⁷ M and 10⁻¹² M, and in yet another embodiment the antibodies will bind with a K_D≦5×10⁻⁹.
• An “antibody” refers to an intact immunoglobulin or to an antigen binding portion thereof that competes with the intact antibody for specific binding, unless otherwise specified. Antigen binding portions can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies. Antigen binding portions include, inter alia, Fab, Fab′, F(ab′)₂, Fv, domain antibodies (dAbs), fragments including complementarity determining regions (CDRs), single-chain antibodies (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies, and polypeptides that contain at least a portion of an immunoglobulin that is sufficient to confer specific antigen binding to the polypeptide.
• A Fab fragment is a monovalent fragment having the V_L, V_H, C_L and C _H1 domains; a F(ab′)₂ fragment is a bivalent fragment having two Fab fragments linked by a disulfide bridge at the hinge region; a Fd fragment has the V_H and C _H1 domains; an Fv fragment has the V_L and V_H domains of a single arm of an antibody; and a dAb fragment has a V_H domain, a V_L domain, or an antigen-binding fragment of a V_H or V_L domain (U.S. Pat. Nos. 6,846,634, and 6,696,245; and US App. Pub. Nos. 05/0202512, 04/0202995, 04/0038291, 04/0009507, 03/0039958, Ward et al., Nature 341:544-546 (1989)).
• A single-chain antibody (scFv) is an antibody in which a V_L and a V_H region are joined via a linker (e.g., a synthetic sequence of amino acid residues) to form a continuous protein chain wherein the linker is long enough to allow the protein chain to fold back on itself and form a monovalent antigen binding site (see, e.g., Bird et al., (1988) Science 242:423-26 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-83). Diabodies are bivalent antibodies comprising two polypeptide chains, wherein each polypeptide chain comprises V_H and V_L domains joined by a linker that is too short to allow for pairing between two domains on the same chain, thus allowing each domain to pair with a complementary domain on another polypeptide chain (see, e.g., Holliger et al., (1993) Proc. Natl. Acad. Sci. USA 90:6444-48, and Poljak et al., (1994) Structure 2:1121-23). If the two polypeptide chains of a diabody are identical, then a diabody resulting from their pairing will have two identical antigen binding sites. Polypeptide chains having different sequences can be used to make a diabody with two different antigen binding sites. Similarly, tribodies and tetrabodies are antibodies comprising three and four polypeptide chains, respectively, and forming three and four antigen binding sites, respectively, which can be the same or different.
• Complementarity determining regions (CDRs) and framework regions (FR) of a given antibody can be identified using the system described by Kabat et al., (1991) “Sequences of Proteins of Immunological Interest”, 5^th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242. Although presented using the Kabat nomenclature system, as desired, the CDRs disclosed herein can also be redefined according an alternative nomenclature scheme, such as that of Chothia (see Chothia & Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670). One or more CDRs can be incorporated into a molecule either covalently or noncovalently to make it an antigen binding protein. An antigen binding protein can incorporate the CDR(s) as part of a larger polypeptide chain, can covalently link the CDR(s) to another polypeptide chain, or can incorporate the CDR(s) noncovalently. The CDRs permit the antigen binding protein to specifically bind to a particular antigen of interest.
• An antigen binding protein can but need not have one or more binding sites. If there is more than one binding site, the binding sites can be identical to one another or can be different. For example, a naturally occurring human immunoglobulin typically has two identical binding sites, while a “bispecific” or “bifunctional” antibody has two different binding sites. Antigen binding proteins of this bispecific form (e.g., those comprising various heavy and light chain CDRs provided herein) comprise aspects of the instant disclosure.
• The term “human antibody” includes all antibodies that have one or more variable and constant regions derived from human immunoglobulin sequences. In one embodiment, all of the variable and constant domains are derived from human immunoglobulin sequences (a fully human antibody). These antibodies can be prepared in a variety of ways, examples of which are described below, including through the immunization with an antigen of interest of a mouse that is genetically modified to express antibodies derived from human heavy and/or light chain-encoding genes, such as a mouse derived from a XENOMOUSE®, ULTIMAB™, HUMAB-MOUSE®, VELOCIMOUSE®, VELOCIMMUNE®, KYMOUSE, or ALIVAMAB system, or derived from human heavy chain transgenic mouse, transgenic rat human antibody repertoire, transgenic rabbit human antibody repertoire or cow human antibody repertoire or HUTARG™ technology. Phage-based approaches can also be employed.
• A humanized antibody has a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and/or additions, such that the humanized antibody is less likely to induce an immune response, and/or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject. In one embodiment, certain amino acids in the framework and constant domains of the heavy and/or light chains of the non-human species antibody are mutated to produce the humanized antibody. In another embodiment, the constant domain(s) from a human antibody are fused to the variable domain(s) of a non-human species. In another embodiment, one or more amino acid residues in one or more CDR sequences of a non-human antibody are changed to reduce the likely immunogenicity of the non-human antibody when it is administered to a human subject, wherein the changed amino acid residues either are not critical for immunospecific binding of the antibody to its antigen, or the changes to the amino acid sequence that are made are conservative changes, such that the binding of the humanized antibody to the antigen is not significantly worse than the binding of the non-human antibody to the antigen. Examples of how to make humanized antibodies can be found in U.S. Pat. Nos. 6,054,297, 5,886,152 and 5,877,293.
• The term “chimeric antibody” refers to an antibody that contains one or more regions from one antibody and one or more regions from one or more other antibodies. In one embodiment, one or more of the CDRs are derived from a human antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In another embodiment, all of the CDRs are derived from a human antibody that binds to a complex β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In another embodiment, the CDRs from more than one human antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are mixed and matched in a chimeric antibody. For instance, a chimeric antibody can comprise a CDR1 from the light chain of a first human antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, a CDR2 and a CDR3 from the light chain of a second human antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and the CDRs from the heavy chain from a third antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Further, the framework regions can be derived from one of the same antibodies that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, from one or more different antibodies, such as a human antibody, or from a humanized antibody. In one example of a chimeric antibody, a portion of the heavy and/or light chain is identical with, homologous to, or derived from an antibody from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with, homologous to, or derived from an antibody or antibodies from another species or belonging to another antibody class or subclass. Also included are fragments of such antibodies that exhibit the desired biological activity (e.g., the ability to specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c).
• The term “light chain” includes a full-length light chain and fragments thereof having sufficient variable region sequence to confer binding specificity. A full-length light chain includes a variable region domain, V_L, and a constant region domain, C_L. The variable region domain of the light chain is at the amino-terminus of the polypeptide. Light chains include kappa (“κ”) chains and lambda (“λ”) chains.
• The term “heavy chain” includes a full-length heavy chain and fragments thereof having sufficient variable region sequence to confer binding specificity. A full-length heavy chain includes a variable region domain, V_H, and three constant region domains, C _H1, C _H2, and C _H3. The V_H domain is at the amino-terminus of the polypeptide, and the C_H domains are at the carboxyl-terminus, with the C _H3 being closest to the carboxy-terminus of the polypeptide. Heavy chains can be of any isotype, including IgG (including IgG1, IgG2, IgG3 and IgG4 subtypes), IgA (including IgA1 and IgA2 subtypes), IgM and IgE.
• The term “immunologically functional fragment” (or simply “fragment”) of an antigen binding protein, e.g., an antibody or immunoglobulin chain (heavy or light chain), as used herein, is an antigen binding protein comprising a portion (regardless of how that portion is obtained or synthesized) of an antibody that lacks at least some of the amino acids present in a full-length chain but which is capable of specifically binding to an antigen. Such fragments are biologically active in that they bind specifically to the target antigen and can compete with other antigen binding proteins, including intact antibodies, for specific binding to a given epitope. In one aspect, such a fragment will retain at least one CDR present in the full-length light or heavy chain, and in some embodiments will comprise a single heavy chain and/or light chain or portion thereof. These biologically active fragments can be produced by recombinant DNA techniques, or can be produced by enzymatic or chemical cleavage of antigen binding proteins, including intact antibodies. Immunologically functional immunoglobulin fragments include, but are not limited to, Fab, Fab′, F(ab′)₂, Fv, domain antibodies and single-chain antibodies, and can be derived from any mammalian source, including but not limited to human, mouse, rat, camelid or rabbit. It is contemplated further that a functional portion of the antigen binding proteins disclosed herein, for example, one or more CDRs, could be covalently bound to a second protein or to a small molecule to create a therapeutic agent directed to a particular target in the body, possessing bifunctional therapeutic properties, or having a prolonged serum half-life.
• An “Fc” region contains two heavy chain fragments comprising the C _H2 and C _H3 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the C _H3 domains.
• An “Fab′ fragment” contains one light chain and a portion of one heavy chain that contains the V_H domain and the C _H1 domain and also 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.
• An “F(ab′)₂ fragment” contains two light chains and two heavy chains containing a portion of the constant region between the C _H1 and C _H2 domains, such that an interchain disulfide bond is formed between the two heavy chains. A F(ab′)₂ fragment thus is composed of two Fab′ fragments that are held together by a disulfide bond between the two heavy chains.
• The “Fv region” comprises the variable regions from both the heavy and light chains, but lacks the constant regions.
• A “domain antibody” is an immunologically functional immunoglobulin fragment containing only the variable region of a heavy chain or the variable region of a light chain. In some instances, two or more V_H regions are covalently joined with a peptide linker to create a bivalent domain antibody. The two V_H regions of a bivalent domain antibody can target the same or different antigens.
• A “hemibody” is an immunologically-functional immunoglobulin construct comprising a complete heavy chain, a complete light chain and a second heavy chain Fc region paired with the Fc region of the complete heavy chain. A linker can, but need not, be employed to join the heavy chain Fc region and the second heavy chain Fc region. In particular embodiments a hemibody is a monovalent form of an antigen binding protein disclosed herein. In other embodiments, pairs of charged residues can be employed to associate one Fc region with the second Fc region.
• A “bivalent antigen binding protein” or “bivalent antibody” comprises two antigen binding sites. In some instances, the two binding sites have the same antigen specificities. Bivalent antigen binding proteins and bivalent antibodies can be bispecific, as described herein, and form aspects of the instant disclosure.
• A “multispecific antigen binding protein” or “multispecific antibody” is one that targets more than one antigen or epitope, and forms another aspect of the instant disclosure.
• A “bispecific,” “dual-specific” or “bifunctional” antigen binding protein or antibody is a hybrid antigen binding protein or antibody, respectively, having two different antigen binding sites. Bispecific antigen binding proteins and antibodies are a species of multispecific antigen binding protein or multispecific antibody and can be produced by a variety of methods including, but not limited to, fusion of hybridomas or linking of Fab′ fragments. See, e.g., Songsivilai and Lachmann, (1990) Clin. Exp. Immunol. 79:315-321; Kostelny et al., (1992) J. Immunol. 148:1547-1553. The two binding sites of a bispecific antigen binding protein or antibody will bind to two different epitopes, which can reside on the same (e.g., β-Klotho, FGFR1c, FGFR2c, or FGFR3c) or different protein targets (e.g., β-Klotho and one of (i) FGFR1c, (ii) FGFR2c, and (iii) FGFR3c).
• The terms “FGF21-like signaling” and “induces FGF21-like signaling,” when applied to an antigen binding protein of the present disclosure, means that the antigen binding protein mimics, or modulates, an in vivo biological effect induced by the binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and induces a biological response that otherwise would result from FGF21 binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in vivo. In assessing the binding and specificity of an antigen binding protein, e.g., an antibody or immunologically functional fragment thereof, an antibody or fragment is deemed to induce a biological response when the response is equal to or greater than 5%, and preferably equal to or greater than 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, of the activity of a wild type FGF21 standard comprising the mature form of SEQ ID NO: 2 (i.e., the mature form of the human FGF21 sequence) and has the following properties: exhibiting an efficacy level of equal to or more than 5% of an FGF21 standard, with an EC₅₀ of equal to or less than 100 nM, e.g., 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM or 10 nM in (1) the recombinant FGF21 receptor-mediated luciferase reporter cell assay of Example 4; (2) ERK-phosphorylation in the recombinant FGF21 receptor mediated cell assay of Example 4; and (3) ERK-phosphorylation in human adipocytes as described in Example 4. The “potency” of an antigen binding protein is defined as exhibiting an EC50 of equal to or less than 100 nM, e.g., 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM and preferably less than 10 nM of the antigen binding protein in the following assays: (1) the recombinant FGF21 receptor mediated luciferase-reporter cell assay of Example 4; (2) the ERK-phosphorylation in the recombinant FGF21 receptor mediated cell assay of Example 4; and (3) ERK-phosphorylation in human adipocytes as described in Example 4.
• It is noted that not all of the antigen binding proteins of the present disclosure induce FGF21-mediated signaling (e.g., that induce agonistic activity), nor is this property desirable in all circumstances. Nevertheless, antigen binding proteins that do not induce FGF21-mediated signaling form aspects of the present disclosure and may be useful as diagnostic reagents or other applications.
• As used herein, the term “FGF21R” means a multimeric receptor complex that FGF21 is known or suspected to form in vivo. In various embodiments, FGF21R comprises (i) an FGFR, e.g., FGFR1c, FGFR2c, FGFR3c or FGFR4, and (ii) β-Klotho.
• The term “polynucleotide” or “nucleic acid” includes both single-stranded and double-stranded nucleotide polymers. The nucleotides comprising the polynucleotide can be ribonucleotides or deoxyribonucleotides or a modified form of either type of nucleotide. Said modifications include base modifications such as bromouridine and inosine derivatives, ribose modifications such as 2′, 3′-dideoxyribose, and internucleotide linkage modifications such as phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phoshoraniladate and phosphoroamidate.
• The term “oligonucleotide” means a polynucleotide comprising 200 or fewer nucleotides. In some embodiments, oligonucleotides are 10 to 60 bases in length. In other embodiments, oligonucleotides are 12, 13, 14, 15, 16, 17, 18, 19, or 20 to 40 nucleotides in length. Oligonucleotides can be single stranded or double stranded, e.g., for use in the construction of a mutant gene. Oligonucleotides can be sense or antisense oligonucleotides. An oligonucleotide can include a label, including a radiolabel, a fluorescent label, a hapten or an antigenic label, for detection assays. Oligonucleotides can be used, for example, as PCR primers, cloning primers or hybridization probes.
• An “isolated nucleic acid molecule” means a DNA or RNA of genomic, mRNA, cDNA, or synthetic origin or some combination thereof which is not associated with all or a portion of a polynucleotide in which the isolated polynucleotide is found in nature, or is linked to a polynucleotide to which it is not linked in nature. For purposes of this disclosure, it is understood that “a nucleic acid molecule comprising” a particular nucleotide sequence does not encompass intact chromosomes. Isolated nucleic acid molecules “comprising” specified nucleic acid sequences can include, in addition to the specified sequences, coding sequences for up to ten or even up to twenty other proteins or portions thereof, or can include operably linked regulatory sequences that control expression of the coding region of the recited nucleic acid sequences, and/or can include vector sequences.
• Unless specified otherwise, the left-hand end of any single-stranded polynucleotide sequence discussed herein is the 5′ end; the left-hand direction of double-stranded polynucleotide sequences is referred to as the 5′ direction. The direction of 5′ to 3′ addition of nascent RNA transcripts is referred to as the transcription direction; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 5′ to the 5′ end of the RNA transcript are referred to as “upstream sequences;” sequence regions on the DNA strand having the same sequence as the RNA transcript that are 3′ to the 3′ end of the RNA transcript are referred to as “downstream sequences.”
• The term “control sequence” refers to a polynucleotide sequence that can affect the expression and processing of coding sequences to which it is ligated. The nature of such control sequences can depend upon the host organism. In particular embodiments, control sequences for prokaryotes can include a promoter, a ribosomal binding site, and a transcription termination sequence. For example, control sequences for eukaryotes can include promoters comprising one or a plurality of recognition sites for transcription factors, transcription enhancer sequences, and transcription termination sequence. “Control sequences” can include leader sequences and/or fusion partner sequences.
• The term “vector” means any molecule or entity (e.g., nucleic acid, plasmid, bacteriophage or virus) used to transfer protein coding information into a host cell.
• The term “expression vector” or “expression construct” refers to a vector that is suitable for transformation of a host cell and contains nucleic acid sequences that direct and/or control (in conjunction with the host cell) expression of one or more heterologous coding regions operatively linked thereto. An expression construct can include, but is not limited to, sequences that affect or control transcription, translation, and, if introns are present, affect RNA splicing of a coding region operably linked thereto.
• As used herein, “operably linked” means that the components to which the term is applied are in a relationship that allows them to carry out their inherent functions under suitable conditions. For example, a control sequence in a vector that is “operably linked” to a protein coding sequence is ligated thereto so that expression of the protein coding sequence is achieved under conditions compatible with the transcriptional activity of the control sequences.
• The term “host cell” means a cell that has been transformed, or is capable of being transformed, with a nucleic acid sequence and thereby expresses a gene of interest. The term includes the progeny of the parent cell, whether or not the progeny is identical in morphology or in genetic make-up to the original parent cell, so long as the gene of interest is present.
• The term “transduction” means the transfer of genes from one bacterium to another, usually by bacteriophage. “Transduction” also refers to the acquisition and transfer of eukaryotic cellular sequences by replication-defective retroviruses.
• The term “transfection” means the uptake of foreign or exogenous DNA by a cell, and a cell has been “transfected” when the exogenous DNA has been introduced inside the cell membrane. A number of transfection techniques are well known in the art and are disclosed herein. See, e.g., Graham et al., (1973) Virology 52:456; Sambrook et al., (2001), supra; Davis et al., (1986) Basic Methods in Molecular Biology, Elsevier; Chu et al., (1981) Gene 13:197. Such techniques can be used to introduce one or more exogenous DNA moieties into suitable host cells.
• The term “transformation” refers to a change in a cell's genetic characteristics, and a cell has been transformed when it has been modified to contain new DNA or RNA. For example, a cell is transformed where it is genetically modified from its native state by introducing new genetic material via transfection, transduction, or other techniques. Following transfection or transduction, the transforming DNA can recombine with that of the cell by physically integrating into a chromosome of the cell, or can be maintained transiently as an episomal element without being replicated, or can replicate independently as a plasmid. A cell is considered to have been “stably transformed” when the transforming DNA is replicated with the division of the cell.
• The terms “polypeptide” or “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms also apply to amino acid polymers in which one or more amino acid residues is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. The terms can also encompass amino acid polymers that have been modified, e.g., by the addition of carbohydrate residues to form glycoproteins, or phosphorylated. Polypeptides and proteins can be produced by a naturally-occurring and non-recombinant cell, or polypeptides and proteins can be produced by a genetically-engineered or recombinant cell. Polypeptides and proteins can comprise molecules having the amino acid sequence of a native protein, or molecules having deletions from, additions to, and/or substitutions of one or more amino acids of the native sequence. The terms “polypeptide” and “protein” encompass antigen binding proteins that specifically or selectively bind to a complex comprising β-Klotho and an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c), or sequences that have deletions from, additions to, and/or substitutions of one or more amino acids of an antigen binding protein that specifically or selectively binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. The term “polypeptide fragment” refers to a polypeptide that has an amino-terminal deletion, a carboxyl-terminal deletion, and/or an internal deletion as compared with the full-length protein. Such fragments can also contain modified amino acids as compared with the full-length protein. In certain embodiments, fragments are about five to 500 amino acids long. For example, fragments can be at least 5, 6, 8, 10, 14, 20, 50, 70, 100, 110, 150, 200, 250, 300, 350, 400, or 450 amino acids long. Useful polypeptide fragments include immunologically functional fragments of antibodies, including binding domains. In the case of an antigen binding protein that binds to a complex β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, useful fragments include but are not limited to a CDR region, a variable domain of a heavy or light chain, a portion of an antibody chain or just its variable region including two CDRs, and the like.
• The term “isolated protein” referred means that a subject protein (1) is free of at least some other proteins with which it would normally be found, (2) is essentially free of other proteins from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (6) does not occur in nature. Typically, an “isolated protein” constitutes at least about 5%, at least about 10%, at least about 25%, or at least about 50% of a given sample. Genomic DNA, cDNA, mRNA or other RNA, of synthetic origin, or any combination thereof can encode such an isolated protein. Preferably, the isolated protein is substantially free from proteins or polypeptides or other contaminants that are found in its natural environment that would interfere with its therapeutic, diagnostic, prophylactic, research or other use.
• A “variant” of a polypeptide (e.g., an antigen binding protein, or an antibody) comprises an amino acid sequence wherein one or more amino acid residues are inserted into, deleted from and/or substituted into the amino acid sequence relative to another polypeptide sequence. Variants include fusion proteins.
• A “derivative” of a polypeptide is a polypeptide (e.g., an antigen binding protein, or an antibody) that has been chemically modified in some manner distinct from insertion, deletion, or substitution variants, e.g., by conjugation to another chemical moiety.
• The term “naturally occurring” as used throughout the specification in connection with biological materials such as polypeptides, nucleic acids, host cells, and the like, refers to materials which are found in nature.
• “Antigen binding region” means a protein, or a portion of a protein, that specifically binds a specified antigen, e.g., a complex comprising β-Klotho and an β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. For example, that portion of an antigen binding protein that contains the amino acid residues that interact with an antigen and confer on the antigen binding protein its specificity and affinity for the antigen is referred to as “antigen binding region.” An antigen binding region typically includes one or more “complementary binding regions” (“CDRs”). Certain antigen binding regions also include one or more “framework” regions. A “CDR” is an amino acid sequence that contributes to antigen binding specificity and affinity. “Framework” regions can aid in maintaining the proper conformation of the CDRs to promote binding between the antigen binding region and an antigen.
• In certain aspects, recombinant antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, are provided. In this context, a “recombinant protein” is a protein made using recombinant techniques, i.e., through the expression of a recombinant nucleic acid as described herein. Methods and techniques for the production of recombinant proteins are well known in the art.
• The term “compete” when used in the context of antigen binding proteins (e.g., neutralizing antigen binding proteins, neutralizing antibodies, agonistic antigen binding proteins, agonistic antibodies and binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c) that compete for the same epitope or binding site on a target means competition between antigen binding proteins as determined by an assay in which the antigen binding protein (e.g., antibody or immunologically functional fragment thereof) under study prevents or inhibits the specific binding of a reference molecule (e.g., a reference ligand, or reference antigen binding protein, such as a reference antibody) to a common antigen (e.g., FGFR1c, FGFR2c, FGFR3c, β-Klotho or a fragment thereof, or a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c). Numerous types of competitive binding assays can be used to determine if a test molecule competes with a reference molecule for binding. Examples of assays that can be employed include solid phase direct or indirect radioimmunoassay (RIA), solid phase direct or indirect enzyme immunoassay (EIA), sandwich competition assay (see, e.g., Stahli et al., (1983) Methods in Enzymology 9:242-253); solid phase direct biotin-avidin EIA (see, e.g., Kirkland et al., (1986) J. Immunol. 137:3614-3619) solid phase direct labeled assay, solid phase direct labeled sandwich assay (see, e.g., Harlow and Lane, (1988) supra); solid phase direct label RIA using 1-125 label (see, e.g., Morel et al., (1988) Molec. Immunol. 25:7-15); solid phase direct biotin-avidin EIA (see, e.g., Cheung, et al., (1990) Virology 176:546-552); and direct labeled RIA (Moldenhauer et al., (1990) Scand. J. Immunol. 32:77-82). Typically, such an assay involves the use of a purified antigen bound to a solid surface or cells bearing either of an unlabelled test antigen binding protein or a labeled reference antigen binding protein. Competitive inhibition is measured by determining the amount of label bound to the solid surface or cells in the presence of the test antigen binding protein. Usually the test antigen binding protein is present in excess. Antigen binding proteins identified by competition assay (competing antigen binding proteins) include antigen binding proteins binding to the same epitope as the reference antigen binding proteins and antigen binding proteins binding to an adjacent epitope sufficiently proximal to the epitope bound by the reference antigen binding protein for steric hindrance to occur. Additional details regarding methods for determining competitive binding are provided in the examples herein. Usually, when a competing antigen binding protein is present in excess, it will inhibit specific binding of a reference antigen binding protein to a common antigen by at least 40%, 45%, 50%, 55%, 60%, 65%, 70% or 75%. In some instance, binding is inhibited by at least 80%, 85%, 90%, 95%, or 97% or more.
• The term “antigen” refers to a molecule or a portion of a molecule capable of being bound by a selective binding agent, such as an antigen binding protein (including, e.g., an antibody or immunological functional fragment thereof), and may also be capable of being used in an animal to produce antibodies capable of binding to that antigen. An antigen can possess one or more epitopes that are capable of interacting with different antigen binding proteins, e.g., antibodies.
• The term “epitope” means the amino acids of a target molecule that are contacted by an antigen binding protein (for example, an antibody) when the antigen binding protein is bound to the target molecule. The term includes any subset of the complete list of amino acids of the target molecule that are contacted when an antigen binding protein, such as an antibody, is bound to the target molecule. An epitope can be contiguous or non-contiguous (e.g., (i) in a single-chain polypeptide, amino acid residues that are not contiguous to one another in the polypeptide sequence but that within in context of the target molecule are bound by the antigen binding protein, or (ii) in a multimeric receptor comprising two or more individual components, e.g., a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, amino acid residues that are present on one or more of the individual components, but which are still bound by the antigen binding protein). In certain embodiments, epitopes can be mimetic in that they comprise a three dimensional structure that is similar to an antigenic epitope used to generate the antigen binding protein, yet comprise none or only some of the amino acid residues found in that epitope used to generate the antigen binding protein. Most often, epitopes reside on proteins, but in some instances can reside on other kinds of molecules, such as nucleic acids. Epitope determinants can include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl or sulfonyl groups, and can have specific three dimensional structural characteristics, and/or specific charge characteristics. Generally, antigen binding proteins specific for a particular target molecule will preferentially recognize an epitope on the target molecule in a complex mixture of proteins and/or macromolecules.
• The term “identity” refers to a relationship between the sequences of two or more polypeptide molecules or two or more nucleic acid molecules, as determined by aligning and comparing the sequences. “Percent identity” means the percent of identical residues between the amino acids or nucleotides in the compared molecules and is calculated based on the size of the smallest of the molecules being compared. For these calculations, gaps in alignments (if any) must be addressed by a particular mathematical model or computer program (i.e., an “algorithm”). Methods that can be used to calculate the identity of the aligned nucleic acids or polypeptides include those described in Computational Molecular Biology, (Lesk, A. M., ed.), (1988) New York: Oxford University Press; Biocomputing Informatics and Genome Projects, (Smith, D. W., ed.), 1993, New York: Academic Press; Computer Analysis of Sequence Data, Part I, (Griffin, A. M., and Griffin, H. G., eds.), 1994, New Jersey: Humana Press; von Heinje, G., (1987) Sequence Analysis in Molecular Biology, New York: Academic Press; Sequence Analysis Primer, (Gribskov, M. and Devereux, J., eds.), 1991, New York: M. Stockton Press; and Carillo et al., (1988) J. Applied Math. 48:1073.
• In calculating percent identity, the sequences being compared are aligned in a way that gives the largest match between the sequences. The computer program used to determine percent identity is the GCG program package, which includes GAP (Devereux et al., (1984) Nucl. Acid Res. 12:387; Genetics Computer Group, University of Wisconsin, Madison, Wis.). The computer algorithm GAP is used to align the two polypeptides or polynucleotides for which the percent sequence identity is to be determined. The sequences are aligned for optimal matching of their respective amino acid or nucleotide (the “matched span”, as determined by the algorithm). A gap opening penalty (which is calculated as 3× the average diagonal, wherein the “average diagonal” is the average of the diagonal of the comparison matrix being used; the “diagonal” is the score or number assigned to each perfect amino acid match by the particular comparison matrix) and a gap extension penalty (which is usually 1/10 times the gap opening penalty), as well as a comparison matrix such as PAM 250 or BLOSUM 62 are used in conjunction with the algorithm. In certain embodiments, a standard comparison matrix (see, Dayhoff et al., (1978) Atlas of Protein Sequence and Structure 5:345-352 for the PAM 250 comparison matrix; Henikoff et al., (1992) Proc. Natl. Acad. Sci. U.S.A. 89:10915-10919 for the BLOSUM 62 comparison matrix) is also used by the algorithm.
• Recommended parameters for determining percent identity for polypeptides or nucleotide sequences using the GAP program are the following:
• Algorithm: Needleman et al., 1970, J. Mol. Biol. 48:443-453;
• Comparison matrix: BLOSUM 62 from Henikoff et al., 1992, supra;
• Gap Penalty: 12 (but with no penalty for end gaps)
• Gap Length Penalty: 4
• Threshold of Similarity: 0
• Certain alignment schemes for aligning two amino acid sequences can result in matching of only a short region of the two sequences, and this small aligned region can have very high sequence identity even though there is no significant relationship between the two full-length sequences. Accordingly, the selected alignment method (e.g., the GAP program) can be adjusted if so desired to result in an alignment that spans at least 50 contiguous amino acids of the target polypeptide.
• As used herein, “substantially pure” means that the described species of molecule is the predominant species present, that is, on a molar basis it is more abundant than any other individual species in the same mixture. In certain embodiments, a substantially pure molecule is a composition wherein the object species comprises at least 50% (on a molar basis) of all macromolecular species present. In other embodiments, a substantially pure composition will comprise at least 80%, 85%, 90%, 95%, or 99% of all macromolecular species present in the composition. In other embodiments, the object species is purified to essential homogeneity wherein contaminating species cannot be detected in the composition by conventional detection methods and thus the composition consists of a single detectable macromolecular species.
• The terms “treat” and “treating” refer to any indicia of success in the treatment or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient's physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and/or a psychiatric evaluation. For example, certain methods presented herein can be employed to treat Type 2 diabetes, obesity and/or dyslipidemia, either prophylactically or as an acute treatment, to decrease plasma glucose levels, to decrease circulating triglyceride levels, to decrease circulating cholesterol levels and/or ameliorate a symptom associated with type 2 diabetes, obesity and dyslipidemia.
• An “effective amount” is generally an amount sufficient to reduce the severity and/or frequency of symptoms, eliminate the symptoms and/or underlying cause, prevent the occurrence of symptoms and/or their underlying cause, and/or improve or remediate the damage that results from or is associated with diabetes, obesity and dyslipidemia. In some embodiments, the effective amount is a therapeutically effective amount or a prophylactically effective amount. A “therapeutically effective amount” is an amount sufficient to remedy a disease state (e.g., diabetes, obesity or dyslipidemia) or symptoms, particularly a state or symptoms associated with the disease state, or otherwise prevent, hinder, retard or reverse the progression of the disease state or any other undesirable symptom associated with the disease in any way whatsoever. A “prophylactically effective amount” is an amount of a pharmaceutical composition that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of diabetes, obesity or dyslipidemia, or reducing the likelihood of the onset (or reoccurrence) of diabetes, obesity or dyslipidemia or associated symptoms. The full therapeutic or prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a therapeutically or prophylactically effective amount can be administered in one or more administrations.
• “Amino acid” takes its normal meaning in the art. The twenty naturally-occurring amino acids and their abbreviations follow conventional usage. See, Immunology—A Synthesis, 2nd Edition, (E. S. Golub and D. R. Green, eds.), Sinauer Associates: Sunderland, Mass. (1991), incorporated herein by reference for any purpose. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids, unnatural or non-naturally occurring or encoded amino acids such as α-,α-disubstituted amino acids, N-alkyl amino acids, and other unconventional amino acids can also be suitable components for polypeptides and are included in the phrase “amino acid.” Examples of non-natural and non-naturally encoded amino acids (which can be substituted for any naturally-occurring amino acid found in any sequence disclosed herein, as desired) include: 4-hydroxyproline, γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, σ-N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left-hand direction is the amino terminal direction and the right-hand direction is the carboxyl-terminal direction, in accordance with standard usage and convention. A non-limiting lists of examples of non-naturally occurring/encoded amino acids that can be inserted into an antigen binding protein sequence or substituted for a wild-type residue in an antigen binding sequence include β-amino acids, homoamino acids, cyclic amino acids and amino acids with derivatized side chains. Examples include (in the L-form or D-form; abbreviated as in parentheses): citrulline (Cit), homocitrulline (hCit), Nα-methylcitrulline (NMeCit), Nα-methylhomocitrulline (Nα-MeHoCit), ornithine (Om), Nα-Methylomithine (Nα-MeOrn or NMeOrn), sarcosine (Sar), homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine (hQ), Nα-methylarginine (NMeR), Nα-methylleucine (Nα-MeL or NMeL), N-methylhomolysine (NMeHoK), Nα-methylglutamine (NMeQ), norleucine (Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic), Octahydroindole-2-carboxylic acid (Oic), 3-(1-naphthy)alanine (1-Nal), 3-(2-naphthyl)alanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic), 2-indanylglycine (IgI), para-iodophenylalanine (pI-Phe), para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine (Guf), glycyllysine (abbreviated “K(Nε-glycyl)” or “K(glycyl)” or “K(gly)”), nitrophenylalanine (nitrophe), aminophenylalanine (aminophe or Amino-Phe), benzylphenylalanine (benzylphe), γ-carboxyglutamic acid (γ-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine (Cpa), α-aminoadipic acid (Aad), Nα-methyl valine (NMeVal), N-α-methyl leucine (NMeLeu), Nα-methylnorleucine (NMeNle), cyclopentylglycine (Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), α, β-diaminopropionoic acid (Dpr), α, γ-diaminobutyric acid (Dab), diaminopropionic acid (Dap), cyclohexylalanine (Cha), 4-methyl-phenylalanine (MePhe), β, β-diphenyl-alanine (BiPhA), aminobutyric acid (Abu), 4-phenyl-phenylalanine (or biphenylalanine; 4Bip), α-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionic acid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid, aminopimelic acid, desmosine, diaminopimelic acid, N-ethylglycine, N-ethylaspargine, hydroxylysine, allo-hydroxylysine, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline, 4-hydroxyproline (Hyp), γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, ω-methylarginine, 4-Amino-O-Phthalic Acid (4APA), and other similar amino acids, and derivatized forms of any of those specifically listed.
II. General Overview
• Antigen-binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are provided herein. A unique property of the antigen binding proteins disclosed herein is the agonistic nature of these proteins, specifically the ability to mimic the in vivo effect of FGF21 and to induce FGF21-like signaling. More remarkably and specifically, some of the antigen binding proteins disclosed herein induce FGF21-like signaling in several in vitro cell-based assay, including the ELK-luciferase reporter assay of Example 4 under the following conditions: (1) the binding to and activity of the FGF21 receptor is β-Klotho dependent; (2) the activity is selective to the FGFR/β-Klotho complex; (3) the binding to the FGFR1c/βKlotho complex triggers FGF21-like signaling pathways; and (4) the potency (EC50) is comparable to a wild-type FGF21 standard comprising the mature form of SEQ ID NO: 2, as measured in the following cell-based assays: (1) the recombinant FGF21 receptor mediated luciferase-reporter cell assay of Example 4; (2) the ERK-phosphorylation in the recombinant FGF21 receptor mediated cell assay of Example 4; and (3) ERK-phosphorylation in human adipocytes as described in more details in Example 6. The disclosed antigen binding proteins, therefore, are expected to exhibit activities in vivo that are consistent with the natural biological function of FGF21. This property makes the disclosed antigen binding proteins viable therapeutics for the treatment of metabolic diseases such as type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, metabolic syndrome and broadly any disease or condition in which it is desirable to mimic or augment the in vivo effects of FGF21.
• In some embodiments of the present disclosure the antigen binding proteins provided can comprise polypeptides into which one or more complementary determining regions (CDRs) can be embedded and/or joined. In such antigen binding proteins, the CDRs can be embedded into a “framework” region, which orients the CDR(s) such that the proper antigen binding properties of the CDR(s) is achieved. In general, such antigen binding proteins that are provided can facilitate or enhance the interaction between an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) and β-Klotho, and can substantially induce FGF21-like signaling. Accordingly, the antigen binding proteins provided herein mimic the in vivo role of FGF21 and are thus “agonistic” and offer potential therapeutic benefit for the range of conditions which benefit from FGF21 therapy, including type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, metabolic syndrome and broadly any disease or condition in which it is desirable to mimic or augment the in vivo effects of FGF21.
• Certain antigen binding proteins described herein are antibodies or are derived from antibodies. In certain embodiments, the polypeptide structure of the antigen binding proteins is based on antibodies, including, but not limited to, monoclonal antibodies, bispecific antibodies, minibodies, domain antibodies, synthetic antibodies (sometimes referred to herein as “antibody mimetics”), chimeric antibodies, humanized antibodies, human antibodies, antibody fusions (sometimes referred to herein as “antibody conjugates”), hemibodies and fragments thereof. The various structures are further described herein below.
• The antigen binding proteins provided herein have been demonstrated to bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and particularly to a complex comprising human β-Klotho and a human FGFR (e.g., a human FGFR1c, a human FGFR2c or a human FGFR3c). As described and shown in the Examples presented herein, based Western blot results, known commercially-available anti-β-Klotho or anti-FGFR1c antibodies bind to denatured β-Klotho or FGFR1c whereas the antigen binding protein (which are agonistic antibodies) do not. Conversely, the provided antigen binding proteins recognize the native structure of the FGFR1c and β-Klotho on the cell surface whereas the commercial antibodies do not. The antigen binding proteins that are provided therefore mimic the natural in vivo biological activity of FGF21. As a consequence, the antigen binding proteins provided herein are capable of activating FGF21-like signaling activity. In particular, the disclosed antigen binding proteins can have one or more of the following activities in vivo: induction of FGF21-like signal transduction pathways, lowering blood glucose levels, lowering circulating lipid levels, improving metabolic parameters and other physiological effects induced in vivo by the formation of the ternary complex of an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c), β-Klotho and FGF21, for example conditions such as type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, and metabolic syndrome.
• The antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are disclosed herein have a variety of utilities. Some of the antigen binding proteins, for instance, are useful in specific binding assays, in the affinity purification of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including the human forms of these disclosed proteins, and in screening assays to identify other agonists of FGF21-like signaling activity.
• The antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are disclosed herein can be used in a variety of treatment applications, as explained herein. For example, certain antigen binding proteins are useful for treating conditions associated with FGF21-like signaling processes in a patient, such as reducing, alleviating, or treating type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, and metabolic syndrome. Other uses for the antigen binding proteins include, for example, diagnosis of diseases or conditions associated with β-Klotho, FGFR1c, FGFR2c, FGFR3c, FGFR4 or FGF21, and screening assays to determine the presence or absence of these molecules. Some of the antigen binding proteins described herein can be useful in treating conditions, symptoms and/or the pathology associated with decreased FGF21-like signaling activity. Exemplary conditions include, but are not limited to, diabetes, obesity, NASH and dyslipidemia.
FGF21
• The antigen binding proteins disclosed herein induce FGF21-mediated signaling, as defined herein. In vivo, the mature form of FGF21 is the active form of the molecule. The nucleotide sequence encoding full length FGF21 is provided; the nucleotides encoding the signal sequence are underlined.

• (SEQ ID NO: 1)

  ATG GAC TCG GAC GAG ACC GGG TTC GAG CAC TCA GGA

  CTG TGG GTT TCT GTG CTG GCT GGT CTT CTG CTG GGA

  GCC TGC CAG GCA CAC CCC ATC CCT GAC TCC AGT CCT

  CTC CTG CAA TTC GGG GGC CAA GTC CGG CAG CGG TAC

  CTC TAC ACA GAT GAT GCC CAG CAG ACA GAA GCC CAC

  CTG GAG ATC AGG GAG GAT GGG ACG GTG GGG GGC GCT

  GCT GAC CAG AGC CCC GAA AGT CTC CTG CAG CTG AAA

  GCC TTG AAG CCG GGA GTT ATT CAA ATC TTG GGA GTC

  AAG ACA TCC AGG TTC CTG TGC CAG CGG CCA GAT GGG

  GCC CTG TAT GGA TCG CTC CAC TTT GAC CCT GAG GCC

  TGC AGC TTC CGG GAG CTG CTT CTT GAG GAC GGA TAC

  AAT GTT TAC CAG TCC GAA GCC CAC GGC CTC CCG CTG

  CAC CTG CCA GGG AAC AAG TCC CCA CAC CGG GAC CCT

  GCA CCC CGA GGA CCA GCT CGC TTC CTG CCA CTA CCA

  GGC CTG CCC CCC GCA CCC CCG GAG CCA CCC GGA ATC

  CTG GCC CCC CAG CCC CCC GAT GTG GGC TCC TCG GAC

  CCT CTG AGC ATG GTG GGA CCT TCC CAG GGC CGA AGC

  CCC AGC TAC GCT TCC TGA

• The amino acid sequence of full length FGF21 is provided; the amino acids that make up the signal sequence are underlined:

• (SEQ ID NO: 2)

  M D S D E T G F E H S G L W V S V L A G L L L G A

  C Q A H P I P D S S P L L Q F G G Q V R Q R Y L Y

  T D D A Q Q T E A H L E I R E D G T V G G A A D Q

  S P E S L L Q L K A L K P G V I Q I L G V K T S R

  F L C Q R P D G A L Y G S L H F D P E A C S F R E

  L L L E D G Y N V Y Q S E A H G L P L H L P G N K

  S P H R D P A P R G P A R F L P L P G L P P A P P

  E P P G I L A P Q P P D V G S S D P L S M V G P S

  Q G R S P S Y A S

FGFR1c
• The antigen binding proteins disclosed herein bind to FGFR1c, in particular human FGFR1c, when associated with β-Klotho. The nucleotide sequence encoding human FGFR1c (GenBank Accession Number NM_023110) is provided:

• (SEQ ID NO: 3)

  ATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAG

  CCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCTGAACAAGC

  CCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCAC

  CCCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGTGC

  AGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCA

  ACCGCACCCGCATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCG

  TGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGCAGCCCCTC

  GGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCC

  CCTCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGAGGA

  GAAAGAAACAGATAACACCAAACCAAACCGTATGCCCGTAGCTCC

  ATATTGGACATCACCAGAAAAGATGGAAAAGAAATTGCATGCAGT

  GCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACA

  CCAAACCCAACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAA

  CCTGACCACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTGGA

  GCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTACAC

  CTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCA

  GCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCA

  GGGTTGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAG

  TTCATGTGTAAGGTGTACAGTGACCCGCAGCCGCACATCCAGTGGC

  TAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAACC

  TGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGA

  CAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGAC

  GCAGGGGAGTATACGTGCTTGGCGGGTAACTCTATCGGACTCTCCC

  ATCACTCTGCATGGTTGACCGTTCTGGAAGCCCTGGAAGAGAGGCC

  GGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTATTGC

  ACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCT

  ACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGA

  TGGCTGTGCACAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGT

  AACAGTGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTT

  CTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAG

  CAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCT

  GCCTCGGGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTG

  CTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGA

  CAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTC

  GGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAATGGA

  GATGATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCT

  GGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTAT

  GCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCC

  CCAGGGCTGGAATACTGCTACAACCCCAGCCACAACCCAGAGGAG

  CAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGCCC

  GAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACC

  TGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGAAGA

  TAGCAGACTTTGGCCTCGCACGGGACATTCACCACATCGACTACTA

  TAAAAAGACAACCAACGGCCGACTGCCTGTGAAGTGGATGGCACC

  CGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTGG

  TCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCC

  ATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAG

  GGTCACCGCATGGACAAGCCCAGTAACTGCACCAACGAGCTGTAC

  ATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCACAGAGACCCA

  CCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGAC

  CTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTAC

  TCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGG

  AGGATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCT

  GCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGC

  TGA.

• The amino acid sequence of human FGFR1c (GenBank Accession Number NP_075598) is provided:

• (SEQ ID NO: 4)

  MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHP

  GDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPA

  DSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEEKETD

  NTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLR

  WLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEY

  GSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQ

  PHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVS

  FEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYC

  TGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRRQVT

  VSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRD

  RLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATE

  KDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLR

  EYLQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASK

  KCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPV

  KWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKL

  LKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIV

  ALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLP

  RHPAQLANGGLKRR.

• The antigen binding proteins described herein bind the extracellular portion of FGFR1c. An example of an extracellular region of FGFR1c is:

• (SEQ ID NO: 5)

  MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHP

  GDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPA

  DSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEEKETD

  NTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLR

  WLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEY

  GSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQ

  PHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVS

  FEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLY.

• As described herein, FGFR1c proteins can also include fragments. As used herein, the terms are used interchangeably to mean a receptor, in particular and unless otherwise specified, a human receptor, that upon association with β-Klotho and FGF21 induces FGF21-like signaling activity.
• The term FGFR1c also includes post-translational modifications of the FGFR1c amino acid sequence, for example, possible N-linked glycosylation sites. Thus, the antigen binding proteins can bind to or be generated from proteins glycosylated at one or more of the positions.
β-Klotho
• The antigen binding proteins disclosed herein bind to β-Klotho, in particular human β-Klotho. The nucleotide sequence encoding human β-Klotho (GenBank Accession Number NM_175737) is provided:

• (SEQ ID NO: 6)

  ATGAAGCCAGGCTGTGCGGCAGGATCTCCAGGGAATGAATGGATT

  TTCTTCAGCACTGATGAAATAACCACACGCTATAGGAATACAATGT

  CCAACGGGGGATTGCAAAGATCTGTCATCCTGTCAGCACTTATTCT

  GCTACGAGCTGTTACTGGATTCTCTGGAGATGGAAGAGCTATATGG

  TCTAAAAATCCTAATTTTACTCCGGTAAATGAAAGTCAGCTGTTTCT

  CTATGACACTTTCCCTAAAAACTTTTTCTGGGGTATTGGGACTGGA

  GCATTGCAAGTGGAAGGGAGTTGGAAGAAGGATGGAAAAGGACCT

  TCTATATGGGATCATTTCATCCACACACACCTTAAAAATGTCAGCA

  GCACGAATGGTTCCAGTGACAGTTATATTTTTCTGGAAAAAGACTT

  ATCAGCCCTGGATTTTATAGGAGTTTCTTTTTATCAATTTTCAATTT

  CCTGGCCAAGGCTTTTCCCCGATGGAATAGTAACAGTTGCCAACGC

  AAAAGGTCTGCAGTACTACAGTACTCTTCTGGACGCTCTAGTGCTT

  AGAAACATTGAACCTATAGTTACTTTATACCACTGGGATTTGCCTTT

  GGCACTACAAGAAAAATATGGGGGGTGGAAAAATGATACCATAAT

  AGATATCTTCAATGACTATGCCACATACTGTTTCCAGATGTTTGGG

  GACCGTGTCAAATATTGGATTACAATTCACAACCCATATCTAGTGG

  CTTGGCATGGGTATGGGACAGGTATGCATGCCCCTGGAGAGAAGG

  GAAATTTAGCAGCTGTCTACACTGTGGGACACAACTTGATCAAGGC

  TCACTCGAAAGTTTGGCATAACTACAACACACATTTCCGCCCACAT

  CAGAAGGGTTGGTTATCGATCACGTTGGGATCTCATTGGATCGAGC

  CAAACCGGTCGGAAAACACGATGGATATATTCAAATGTCAACAAT

  CCATGGTTTCTGTGCTTGGATGGTTTGCCAACCCTATCCATGGGGAT

  GGCGACTATCCAGAGGGGATGAGAAAGAAGTTGTTCTCCGTTCTAC

  CCATTTTCTCTGAAGCAGAGAAGCATGAGATGAGAGGCACAGCTG

  ATTTCTTTGCCTTTTCTTTTGGACCCAACAACTTCAAGCCCCTAAAC

  ACCATGGCTAAAATGGGACAAAATGTTTCACTTAATTTAAGAGAAG

  CGCTGAACTGGATTAAACTGGAATACAACAACCCTCGAATCTTGAT

  TGCTGAGAATGGCTGGTTCACAGACAGTCGTGTGAAAACAGAAGA

  CACCACGGCCATCTACATGATGAAGAATTTCCTCAGCCAGGTGCTT

  CAAGCAATAAGGTTAGATGAAATACGAGTGTTTGGTTATACTGCCT

  GGTCTCTCCTGGATGGCTTTGAATGGCAGGATGCTTACACCATCCG

  CCGAGGATTATTTTATGTGGATTTTAACAGTAAACAGAAAGAGCGG

  AAACCTAAGTCTTCAGCACACTACTACAAACAGATCATACGAGAA

  AATGGTTTTTCTTTAAAAGAGTCCACGCCAGATGTGCAGGGCCAGT

  TTCCCTGTGACTTCTCCTGGGGTGTCACTGAATCTGTTCTTAAGCCC

  GAGTCTGTGGCTTCGTCCCCACAGTTCAGCGATCCTCATCTGTACGT

  GTGGAACGCCACTGGCAACAGACTGTTGCACCGAGTGGAAGGGGT

  GAGGCTGAAAACACGACCCGCTCAATGCACAGATTTTGTAAACATC

  AAAAAACAACTTGAGATGTTGGCAAGAATGAAAGTCACCCACTAC

  CGGTTTGCTCTGGATTGGGCCTCGGTCCTTCCCACTGGCAACCTGTC

  CGCGGTGAACCGACAGGCCCTGAGGTACTACAGGTGCGTGGTCAG

  TGAGGGGCTGAAGCTTGGCATCTCCGCGATGGTCACCCTGTATTAT

  CCGACCCACGCCCACCTAGGCCTCCCCGAGCCTCTGTTGCATGCCG

  ACGGGTGGCTGAACCCATCGACGGCCGAGGCCTTCCAGGCCTACGC

  TGGGCTGTGCTTCCAGGAGCTGGGGGACCTGGTGAAGCTCTGGATC

  ACCATCAACGAGCCTAACCGGCTAAGTGACATCTACAACCGCTCTG

  GCAACGACACCTACGGGGCGGCGCACAACCTGCTGGTGGCCCACG

  CCCTGGCCTGGCGCCTCTACGACCGGCAGTTCAGGCCCTCACAGCG

  CGGGGCCGTGTCGCTGTCGCTGCACGCGGACTGGGCGGAACCCGCC

  AACCCCTATGCTGACTCGCACTGGAGGGCGGCCGAGCGCTTCCTGC

  AGTTCGAGATCGCCTGGTTCGCCGAGCCGCTCTTCAAGACCGGGGA

  CTACCCCGCGGCCATGAGGGAATACATTGCCTCCAAGCACCGACGG

  GGGCTTTCCAGCTCGGCCCTGCCGCGCCTCACCGAGGCCGAAAGGA

  GGCTGCTCAAGGGCACGGTCGACTTCTGCGCGCTCAACCACTTCAC

  CACTAGGTTCGTGATGCACGAGCAGCTGGCCGGCAGCCGCTACGAC

  TCGGACAGGGACATCCAGTTTCTGCAGGACATCACCCGCCTGAGCT

  CCCCCACGCGCCTGGCTGTGATTCCCTGGGGGGTGCGCAAGCTGCT

  GCGGTGGGTCCGGAGGAACTACGGCGACATGGACATTTACATCAC

  CGCCAGTGGCATCGACGACCAGGCTCTGGAGGATGACCGGCTCCG

  GAAGTACTACCTAGGGAAGTACCTTCAGGAGGTGCTGAAAGCATA

  CCTGATTGATAAAGTCAGAATCAAAGGCTATTATGCATTCAAACTG

  GCTGAAGAGAAATCTAAACCCAGATTTGGATTCTTCACATCTGATT

  TTAAAGCTAAATCCTCAATACAATTTTACAACAAAGTGATCAGCAG

  CAGGGGCTTCCCTTTTGAGAACAGTAGTTCTAGATGCAGTCAGACC

  CAAGAAAATACAGAGTGCACTGTCTGCTTATTCCTTGTGCAGAAGA

  AACCACTGATATTCCTGGGTTGTTGCTTCTTCTCCACCCTGGTTCTA

  CTCTTATCAATTGCCATTTTTCAAAGGCAGAAGAGAAGAAAGTTTT

  GGAAAGCAAAAAACTTACAACACATACCATTAAAGAAAGGCAAGA

  GAGTTGTTAGCTAA.

• The amino acid sequence of full length human β-Klotho (GenBank Accession Number NP_783864) is provided:

• (SEQ ID NO: 7)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRA

  VTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVE

  GSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGV

  SFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYH

  WDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNP

  YLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTH

  FRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIH

  GDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLN

  TMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDT

  TAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGL

  FYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFS

  WGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRP

  AQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQA

  LRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPST

  AEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHN

  LLVAHALAWRLYDRQFRPSQRGAVSLSLHADWAEPANPYADSHWRA

  AERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEA

  ERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLS

  SPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRK

  YYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAK

  SSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGC

  CFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS.

• The antigen binding proteins described herein bind the extracellular portion of β-Klotho. An example of an extracellular region of β-Klotho is:

• (SEQ ID NO: 8)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRA

  VTGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVE

  GSWKKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGV

  SFYQFSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYH

  WDLPLALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNP

  YLVAWHGYGTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTH

  FRPHQKGWLSITLGSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIH

  GDGDYPEGMRKKLFSVLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLN

  TMAKMGQNVSLNLREALNWIKLEYNNPRILIAENGWFTDSRVKTEDT

  TAIYMMKNFLSQVLQAIRLDEIRVFGYTAWSLLDGFEWQDAYTIRRGL

  FYVDFNSKQKERKPKSSAHYYKQIIRENGFSLKESTPDVQGQFPCDFS

  WGVTESVLKPESVASSPQFSDPHLYVWNATGNRLLHRVEGVRLKTRP

  AQCTDFVNIKKQLEMLARMKVTHYRFALDWASVLPTGNLSAVNRQA

  LRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLPEPLLHADGWLNPST

  AEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYNRSGNDTYGAAHN

  LLVAHALAWRLYDRQFRPSQRGAVSLSLHADWAEPANPYADSHWRA

  AERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSALPRLTEA

  ERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQDITRLS

  SPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRLRK

  YYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAK

  SSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKP.

• The murine form of β-Klotho, and fragments and subsequences thereof, can be of use in studying and/or constructing the molecules provided herein. The nucleotide sequence encoding murine β-Klotho (GenBank Accession Number NM_031180) is provided:

• (SEQ ID NO: 9)

  ATGAAGACAGGCTGTGCAGCAGGGTCTCCGGGGAATGAATGGATT

  TTCTTCAGCTCTGATGAAAGAAACACACGCTCTAGGAAAACAATGT

  CCAACAGGGCACTGCAAAGATCTGCCGTGCTGTCTGCGTTTGTTCT

  GCTGCGAGCTGTTACCGGCTTCTCCGGAGACGGGAAAGCAATATGG

  GATAAAAAACAGTACGTGAGTCCGGTAAACCCAAGTCAGCTGTTCC

  TCTATGACACTTTCCCTAAAAACTTTTCCTGGGGCGTTGGGACCGG

  AGCATTTCAAGTGGAAGGGAGTTGGAAGACAGATGGAAGAGGACC

  CTCGATCTGGGATCGGTACGTCTACTCACACCTGAGAGGTGTCAAC

  GGCACAGACAGATCCACTGACAGTTACATCTTTCTGGAAAAAGACT

  TGTTGGCTCTGGATTTTTTAGGAGTTTCTTTTTATCAGTTCTCAATCT

  CCTGGCCACGGTTGTTTCCCAATGGAACAGTAGCAGCAGTGAATGC

  GCAAGGTCTCCGGTACTACCGTGCACTTCTGGACTCGCTGGTACTT

  AGGAATATCGAGCCCATTGTTACCTTGTACCATTGGGATTTGCCTCT

  GACGCTCCAGGAAGAATATGGGGGCTGGAAAAATGCAACTATGAT

  AGATCTCTTCAACGACTATGCCACATACTGCTTCCAGACCTTTGGA

  GACCGTGTCAAATATTGGATTACAATTCACAACCCTTACCTTGTTGC

  TTGGCATGGGTTTGGCACAGGTATGCATGCACCAGGAGAGAAGGG

  AAATTTAACAGCTGTCTACACTGTGGGACACAACCTGATCAAGGCA

  CATTCGAAAGTGTGGCATAACTACGACAAAAACTTCCGCCCTCATC

  AGAAGGGTTGGCTCTCCATCACCTTGGGGTCCCATTGGATAGAGCC

  AAACAGAACAGACAACATGGAGGACGTGATCAACTGCCAGCACTC

  CATGTCCTCTGTGCTTGGATGGTTCGCCAACCCCATCCACGGGGAC

  GGCGACTACCCTGAGTTCATGAAGACGGGCGCCATGATCCCCGAGT

  TCTCTGAGGCAGAGAAGGAGGAGGTGAGGGGCACGGCTGATTTCT

  TTGCCTTTTCCTTCGGGCCCAACAACTTCAGGCCCTCAAACACCGTG

  GTGAAAATGGGACAAAATGTATCACTCAACTTAAGGCAGGTGCTG

  AACTGGATTAAACTGGAATACGATGACCCTCAAATCTTGATTTCGG

  AGAACGGCTGGTTCACAGATAGCTATATAAAGACAGAGGACACCA

  CGGCCATCTACATGATGAAGAATTTCCTAAACCAGGTTCTTCAAGC

  AATAAAATTTGATGAAATCCGCGTGTTTGGTTATACGGCCTGGACT

  CTCCTGGATGGCTTTGAGTGGCAGGATGCCTATACGACCCGACGAG

  GGCTGTTTTATGTGGACTTTAACAGTGAGCAGAAAGAGAGGAAAC

  CCAAGTCCTCGGCTCATTACTACAAGCAGATCATACAAGACAACGG

  CTTCCCTTTGAAAGAGTCCACGCCAGACATGAAGGGTCGGTTCCCC

  TGTGATTTCTCTTGGGGAGTCACTGAGTCTGTTCTTAAGCCCGAGTT

  TACGGTCTCCTCCCCGCAGTTTACCGATCCTCACCTGTATGTGTGGA

  ATGTCACTGGCAACAGATTGCTCTACCGAGTGGAAGGGGTAAGGCT

  GAAAACAAGACCATCCCAGTGCACAGATTATGTGAGCATCAAAAA

  ACGAGTTGAAATGTTGGCAAAAATGAAAGTCACCCACTACCAGTTT

  GCTCTGGACTGGACCTCTATCCTTCCCACTGGCAATCTGTCCAAAGT

  TAACAGACAAGTGTTAAGGTACTATAGGTGTGTGGTGAGCGAAGG

  ACTGAAGCTGGGCGTCTTCCCCATGGTGACGTTGTACCACCCAACC

  CACTCCCATCTCGGCCTCCCCCTGCCACTTCTGAGCAGTGGGGGGT

  GGCTAAACATGAACACAGCCAAGGCCTTCCAGGACTACGCTGAGC

  TGTGCTTCCGGGAGTTGGGGGACTTGGTGAAGCTCTGGATCACCAT

  CAATGAGCCTAACAGGCTGAGTGACATGTACAACCGCACGAGTAA

  TGACACCTACCGTGCAGCCCACAACCTGATGATCGCCCATGCCCAG

  GTCTGGCACCTCTATGATAGGCAGTATAGGCCGGTCCAGCATGGGG

  CTGTGTCGCTGTCCTTACATTGCGACTGGGCAGAACCTGCCAACCC

  CTTTGTGGATTCACACTGGAAGGCAGCCGAGCGCTTCCTCCAGTTT

  GAGATCGCCTGGTTTGCAGATCCGCTCTTCAAGACTGGCGACTATC

  CATCGGTTATGAAGGAATACATCGCCTCCAAGAACCAGCGAGGGC

  TGTCTAGCTCAGTCCTGCCGCGCTTCACCGCGAAGGAGAGCAGGCT

  GGTGAAGGGTACCGTCGACTTCTACGCACTGAACCACTTCACTACG

  AGGTTCGTGATACACAAGCAGCTGAACACCAACCGCTCAGTTGCAG

  ACAGGGACGTCCAGTTCCTGCAGGACATCACCCGCCTAAGCTCGCC

  CAGCCGCCTGGCTGTAACACCCTGGGGAGTGCGCAAGCTCCTTGCG

  TGGATCCGGAGGAACTACAGAGACAGGGATATCTACATCACAGCC

  AATGGCATCGATGACCTGGCTCTAGAGGATGATCAGATCCGAAAGT

  ACTACTTGGAGAAGTATGTCCAGGAGGCTCTGAAAGCATATCTCAT

  TGACAAGGTCAAAATCAAAGGCTACTATGCATTCAAACTGACTGAA

  GAGAAATCTAAGCCTAGATTTGGATTTTTCACCTCTGACTTCAGAG

  CTAAGTCCTCTGTCCAGTTTTACAGCAAGCTGATCAGCAGCAGTGG

  CCTCCCCGCTGAGAACAGAAGTCCTGCGTGTGGTCAGCCTGCGGAA

  GACACAGACTGCACCATTTGCTCATTTCTCGTGGAGAAGAAACCAC

  TCATCTTCTTCGGTTGCTGCTTCATCTCCACTCTGGCTGTACTGCTAT

  CCATCACCGTTTTTCATCATCAAAAGAGAAGAAAATTCCAGAAAGC

  AAGGAACTTACAAAATATACCATTGAAGAAAGGCCACAGCAGAGT

  TTTCAGCTAA.

• The amino acid sequence of full length murine β-Klotho (GenBank Accession Number NP_112457) is provided:

• (SEQ ID NO: 10)

  MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLR

  AVTGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQ

  VEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALD

  FLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIV

  TLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWI

  TIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHN

  YDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWF

  ANPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRP

  SNTVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTED

  TTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRR

  GLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFPCD

  FSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKT

  RPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQ

  VLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMN

  TAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAA

  HNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSH

  WKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPR

  FTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDI

  TRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQI

  RKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFR

  AKSSVQFYSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFF

  GCCFISTLAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS.

• As described herein, β-Klotho proteins can also include fragments. As used herein, the terms are used interchangeably to mean a co-receptor, in particular and unless otherwise specified, a human co-receptor, that upon association with FGFR1c and FGF21 induces FGF21-like signaling activity.
• The term β-Klotho also includes post-translational modifications of the β-Klotho amino acid sequence, for example, possible N-linked glycosylation sites. Thus, the antigen binding proteins can bind to or be generated from proteins glycosylated at one or more of the positions.
• Antigen Binding Proteins that Specifically Bind to a Complex Comprising β-Klotho and an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c)
• A variety of selective binding agents useful for modulating FGF21-like signaling are provided. These agents include, for instance, antigen binding proteins that contain an antigen binding domain (e.g., single chain antibodies, domain antibodies, hemibodies, immunoadhesions, and polypeptides with an antigen binding region) and specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, in particular a complex comprising human β-Klotho and a human FGFR (e.g., human FGFR1c, human FGFR2c or human FGFR3c). Some of the agents, for example, are useful in mimicking the signaling effect generated in vivo by the association of an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) with β-Klotho and with FGF21, and can thus be used to enhance or modulate one or more activities associated with FGF21-like signaling.
• In general, the antigen binding proteins that are provided typically comprise one or more CDRs as described herein (e.g., 1, 2, 3, 4, 5 or 6 CDRs). In some embodiments the antigen binding proteins are naturally expressed by clones, while in other embodiments, the antigen binding protein can comprise (a) a polypeptide framework structure and (b) one or more CDRs that are inserted into and/or joined to the polypeptide framework structure. In some of these embodiments a CDR forms a component of a heavy or light chains expressed by the clones described herein; in other embodiments a CDR can be inserted into a framework in which the CDR is not naturally expressed. A polypeptide framework structure can take a variety of different forms. For example, a polypeptide framework structure can be, or comprise, the framework of a naturally occurring antibody, or fragment or variant thereof, or it can be completely synthetic in nature. Examples of various antigen binding protein structures are further described below.
• In some embodiments in which the antigen binding protein comprises (a) a polypeptide framework structure and (b) one or more CDRs that are inserted into and/or joined to the polypeptide framework structure, the polypeptide framework structure of an antigen binding protein is an antibody or is derived from an antibody, including, but not limited to, monoclonal antibodies, bispecific antibodies, minibodies, domain antibodies, synthetic antibodies (sometimes referred to herein as “antibody mimetics”), chimeric antibodies, humanized antibodies, antibody fusions (sometimes referred to as “antibody conjugates”), and portions or fragments of each, respectively. In some instances, the antigen binding protein is an immunological fragment of an antibody (e.g., a Fab, a Fab′, a F(ab′)₂, or a scFv).
• Certain of the antigen binding proteins as provided herein specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including the human forms of these proteins. In one embodiment, an antigen binding protein specifically binds to both human FGFR1c comprising the amino acid sequence of SEQ ID NO: 4, and human β-Klotho comprising the amino acid sequence of SEQ ID NO: 7, and in another embodiment an antigen binding protein specifically binds to both human FGFR1c comprising the amino acid sequence of SEQ ID NO: 4 and human β-Klotho having the amino acid sequence of SEQ ID NO: 7 and induces FGF21-like signaling. Thus, an antigen binding protein can, but need not, induce FGF21-like signaling.
Antigen Binding Protein Structure
• Some of the antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, including the human forms of these proteins, provided herein have a structure typically associated with naturally occurring antibodies. The structural units of these antibodies typically comprise one or more tetramers, each composed of two identical couplets of polypeptide chains, though some species of mammals also produce antibodies having only a single heavy chain. In a typical antibody, each pair or couplet includes one full-length “light” chain (in certain embodiments, about 25 kDa) and one full-length “heavy” chain (in certain embodiments, about 50-70 kDa). Each individual immunoglobulin chain is composed of several “immunoglobulin domains,” each consisting of roughly 90 to 110 amino acids and expressing a characteristic folding pattern. These domains are the basic units of which antibody polypeptides are composed. The amino-terminal portion of each chain typically includes a variable domain that is responsible for antigen recognition. The carboxy-terminal portion is more conserved evolutionarily than the other end of the chain and is referred to as the “constant region” or “C region”. Human light chains generally are classified as kappa (“κ”) and lambda (“λ”) light chains, and each of these contains one variable domain and one constant domain. Heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon chains, and these define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. IgG has several subtypes, including, but not limited to, IgG1, IgG2, IgG3, and IgG4. IgM subtypes include IgM, and IgM2. IgA subtypes include IgA1 and IgA2. In humans, the IgA and IgD isotypes contain four heavy chains and four light chains; the IgG and IgE isotypes contain two heavy chains and two light chains; and the IgM isotype contains five heavy chains and five light chains. The heavy chain C region typically comprises one or more domains that can be responsible for effector function. The number of heavy chain constant region domains will depend on the isotype. IgG heavy chains, for example, each contain three C region domains known as C _H1, C _H2 and C _H3. The antibodies that are provided can have any of these isotypes and subtypes. In certain embodiments, an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c is an antibody of the IgG1, IgG2, or IgG4 subtype.
• In full-length light and heavy chains, the variable and constant regions are joined by a “J” region of about twelve or more amino acids, with the heavy chain also including a “D” region of about ten more amino acids. See, e.g., Fundamental Immunology, 2nd ed., Ch. 7 (Paul, W., ed.) 1989, New York: Raven Press (hereby incorporated by reference in its entirety for all purposes). The variable regions of each light/heavy chain pair typically form the antigen binding site.
• One example of an IgG2 heavy constant domain of an exemplary monoclonal antibody that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acid sequence:

• (SEQ ID NO: 11)

  ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

  VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT

  VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

  HEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDW

  LNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN

  QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

  LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.

• One example of a kappa light constant domain of an exemplary monoclonal antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acid sequence:

• (SEQ ID NO: 12)

  TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

  GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

  VTKSFNRGEC.

• One example of a lambda light constant domain of an exemplary monoclonal antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has the amino acid sequence:

• (SEQ ID NO: 13)

  QPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKA

  GVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA

  PTECS.

• Variable regions of immunoglobulin chains generally exhibit the same overall structure, comprising relatively conserved framework regions (FR) joined by three hypervariable regions, more often called “complementarity determining regions” or CDRs. The CDRs from the two chains of each heavy chain/light chain pair mentioned above typically are aligned by the framework regions to form a structure that binds specifically with a specific epitope on the target protein (e.g., a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. From N-terminal to C-terminal, naturally-occurring light and heavy chain variable regions both typically conform with the following order of these elements: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. A numbering system has been devised for assigning numbers to amino acids that occupy positions in each of these domains. This numbering system is defined in Kabat et al., (1991) “Sequences of Proteins of Immunological Interest”, 5th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242. Although presented using the Kabat nomenclature system, as desired, the CDRs disclosed herein can also be redefined according an alternative nomenclature scheme, such as that of Chothia (see Chothia & Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670).
• The various heavy chain and light chain variable regions of antigen binding proteins provided herein are depicted in Table 2. Each of these variable regions can be attached to the disclosed heavy and light chain constant regions to form a complete antibody heavy and light chain, respectively. Further, each of the so-generated heavy and light chain sequences can be combined to form a complete antibody structure. It should be understood that the heavy chain and light chain variable regions provided herein can also be attached to other constant domains having different sequences than the exemplary sequences listed above.
• Specific examples of some of the full length light and heavy chains of the antibodies that are provided and their corresponding amino acid sequences are summarized in Tables 1A and 1B. Table 1A shows exemplary light chain sequences, and Table 1B shows exemplary heavy chain sequences.

• TABLE 1A
  Exemplary Antibody Light Chain Sequences

  Contained		SEQ ID
  in Clone	Designation	NO:	Amino Acid Sequence

  63E6	L6	14	DIQMTQSPSSLSASVGDRVTITCRTSQSISSYL
  			NWYQQKPGKAPNLLIYAASSLQSGVPSRFSG
  			SGSGTDFTLTISGLQPEDFSTYYCQQSYSTSL
  			TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  66F7	L7	15	DIQMTQSPSSLSASVGDRVTITCRTSQSISNY
  			LNVVYQQKPGKAPNLLIYAASSLQSGVPSRFS
  			GSGSGTDFTLTISGLQPEDFSTYYCQQSYSTS
  			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  66D4	L18	16	DIQMTQSPSSLSASVGDRITITCRASQIISRYL
  			NWYQQNPGKAPKLLISAASSLQSGVPSRFSG
  			SGSGPDFTLTISSLQPEDFTTYYCQQSYSSPLT
  			FGGGTKVEVKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  66B4	L11	17	DIQMTQSPSSVSSSVGDRVTITCRASQGISRW
  			LAWYQQKPGKAPKLLIYAASSLKSGVPSRFS
  			GSGSGTDFTLTISSLQPEDFATYYCQQANSFP
  			PTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  65B1	L19	18	DIQMTQSPSSLSASVGDRVTITCRASQNINNY
  			LNWYRQKPGKAPELLIYTTSSLQSGVPSRFS
  			GSGSGTDFTLTISSLETEDFETYYCQQSYSTP
  			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  65B4	L21	19	SYVLTQPPSVSVAPGQTARITCGGNNIGSKSV
  			QWYQQKPGQAPVLVVYDDSDRPSGIPERFS
  			GSNSGNTASLTISRVEAGDEADYYCQVWDS
  			SSDHVVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  67A4	L20	20	SYVLTQPPSVSVAPGQTARITCGGNNIGSKSV
  			HWYQQKPGQAPVLVVYDDSDRPSGIPERFS
  			GSNSGNTATLTISRVEAGDEADYYCQVWDS
  			SSDHVVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  63A10v1	L22	21	SYELTQPHSVSVATAQMARITCGGNNIGSKA
  			VHWYQQKPGQDPVLVIYCDSNRPSGIPER
  			FSGSNPGNTATLTISRIEAGDEADYYCQVWD
  			SSSDGVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  63A10v2	L101	1835	SYELTQPHSVSVATAQMARITCGGNNIGSKA
  			VHWYQQKPGQDPVLVIYCDSNRPSGIPER
  			FSGSNPGNTATLTISRIEAGDEADYYCQAWD
  			STTVVFGGGTKLTVLGQPKANPTVTLFPPSS
  			EELQANKATLVCLISDFYPGAVTVAWKADG
  			SPVKAGVETTKPSKQSNNKYAASSYLSLTPE
  			QWKSHRSYSCQVTHEGSTVEKTVAPTECS
  63A10v3	L102	1836	SYELTQPPSVSVSPGQTANITCSGDKLGNRY
  			TCWYQQKSGQSPVLVIYQDSERPSGIPER
  			FSGSNSGNTATLTISGTQAMDEADYYCQAW
  			DSTTVVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  65H11v1	L23	22	SYELTQPHSVSVATAQMARITCGGNNIGSKT
  			VHWFQQKPGQDPVLVIYSDSNRPSGIPERFS
  			GSNPGNTATLTISRIEAGDEADYYCQVWDSS
  			CDGVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  65H11v2	L103	1837	SYELTQPPSVSVSPGQTANITCSGDKLGDRY
  			VCWYQQKPGQSPVLVIYQDSKRPSGIPEQFS
  			GSNSGNTATLTISGTQAIDEADYYCQAWDSI
  			TVVFGGGTKLTVLGQPKANPTVTLFPPSSEE
  			LQANKATLVCLISDFYPGAVTVAWKADGSP
  			VKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  67G10v1	L9	23	SYELTQPHSVSVATAQMARITCGGNNIGSKA
  			VHWYQQKPGQDPVLVIYSDSNRPSGIPERFS
  			GSNPGNTATLTISRIEAGDEADYYCQVWDSS
  			SDGVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  67G10v2	L10	24	SYELTQPPSVSVSPGQTASITCSGDKLGDKY
  			ACWYQQKPGQSPVLVIYQDNERPSGIPERFS
  			GSNSGNTATLTISGTQAMDEADYYCQAWDS
  			TTVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  64C8	L24	25	DVVMTQSPLSLPVTLGQPASISRRSSPSLVYS
  			DGNTYLNCFQQRPGHSPRRLIYKGSNWDSG
  			VPDRFSGSGSGTDFTLKISRVEAEDVGIYYCI
  			QDTHWPTCSFGQGTKLEIKRTVAAPSVFIFPP
  			SDEQLKSGTASVVCLLNNFYPREAKVQWKV
  			DNALQSGNSQESVTEQDSKDSTYSLSSTLTL
  			SKADYEKHKVYACEVTHQGLSSPVTKSFNR
  			GEC
  64A8	L1	26	DIQMTQSPSSLSASVGDRVTITCRASQDIRND
  67B4			LGWYQQKPGKAPKRLIYAASNLQRGVPSRF
  			SGSGSGTEFTLTISTLQPEDFATYSCLQHNSY
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  63G8v1	L104	1838	DIQMTQSPSSLSASVGDRVTITCRASQDIRND
  			LGWYQQKPGKAPKRLIYAASNLQRGVPSRF
  			SGSGSGTEFTLTISTLQPDDFATYSCLQHNSY
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  63G8v2	L105	1839	DIQMTQSPSSLSASVGDRVTITCRASQGIRSG
  			LGWYQQKPGKAPKRLIYAASNLQRGVPSRF
  			SGSGSGTEFTLTVSSLQPEDFATYSCLQHNSY
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  63G8v3	L106	1840	DIQMTQSPSSLSASVGDRVTITCRASQGIRSG
  			LGWYQQKPGKAPKRLIYAASNLQRGVPSRF
  			SGSGSGTEFTLTVSSLQPEDFATYSCLQHNTY
  			PLTFGGGTKGEIRRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  66G2	L12	27	DIQMTQSPSSLSASVGDRVTITCRASQGIRND
  			LGWYQQKPGKAPKRLIYAASNLQSGVPSRFS
  			GSGSGTKFTLTINSLQPEDFATYYCLQLNGY
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  68D3v1	L2	28	DIQMTQSPSSLSASVGDRVTITCRASQDIRND
  68D3v2			LGWYQQKPGKAPKRLIYAASNLQRGVPSRF
  			SGSGSGTEFTLTISTLQPDDFATYSCLQHNSY
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  65D1	L27	29	SYDLTQPPSVSVSPGQTASITCSGDKLGDKY
  			VCWYQQKPGQSPVLVIYQDSKRPSGIPERFS
  			GSNSGNTATLTISGIQAMDEADYYCQAWDS
  			RVFGGGTKLTVLGQPKANPTVTLFPPSSEEL
  			QANKATLVCLISDFYPGAVTVAWKADGSPV
  			KAGVETTKPSKQSNNKYAASSYLSLTPEQW
  			KSHRSYSCQVTHEGSTVEKTVAPTECS
  64H5	L8	30	SYEMTQPLSVSVALGQTARITCGGNNIGSKN
  65G4			VHWYQQKPGQAPVLVIYRDSKRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYYCQVWDS
  			SSVVFGGGTKLTVLGQPKANPTVTLFPPSSEE
  			LQANKATLVCLISDFYPGAVTVAWKADGSP
  			VKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  65D4	L26	31	SYELTQPLSVSVALGQTARIPCGGNDIGSKN
  			VHWYQQKPGQAPVLVIYRDRNRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYYCQVWDS
  			NPVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  65E3	L25	32	SYELTQPLSVSVALGQTARITCGGNNIGSKN
  			VHWYQQKPGQAPVLVIYRDRNRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYYCQVWDS
  			STVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  67G8	L28	33	SYELTQPLSVSVALGQTARITCGGNNIGSYN
  			VFWYQQKPGQAPVLVIYRDSKRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYHCQVWDS
  			STVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  65B7v1	L29	34	EIVLTQSPGTLSLSPGERATLSCRASQSVSSIY
  			LAWYQQKPGQAPRLLIYGASSRATGIPDRFS
  			GSGSGTDFTLTISRLEPEDFAVYYCQQYGSSC
  			SFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  65B7v2	L107	1841	DVVMTQSPLSLPVTLGQPASISYRSSQSLVYS
  			DGDTYLNWFQQRPGQSPRRLIYKVSNWDSG
  			VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
  			MQGTHWRGWTFGQGTKVEIKRTVAAPSVFI
  			FPPSDEQLKSGTASVVCLLNNFYPREAKVQ
  			WKVDNALQSGNSQESVTEQDSKDSTYSLSS
  			TLTLSKADYEKHKVYACEVTHQGLSSPVTK
  			SFNRGEC
  63B6	L4	35	EIVLTQSPGTLSLSPGERATLSCRASQSVSNS
  64D4			YLAWYQQKPGQAPRLLIYGAFSRATGIPDRF
  			SGSGSGTDFTLTISRLEPEDFAVYYCQQFGRS
  			FTFGGGTKVEIRRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  63F5	L14	36	EVVLTQSPGTLSLSPGERATLSCRASQTVRN
  			NYLAWYQQQPGQAPRLLIFGASSRATGIPDR
  			FSGSGSGTDFTLTISRLEPEDFAVYYCQQFGS
  			SLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  65E8	L3	37	EIVLTQSPGTLSLSPGERATLSCRASQSVRNS
  63H11			YLAWYQQQPGQAPRLLIYGAFSRASGIPDRF
  64E6			SGSGSGTDFTLTISRLEPEDFAVYYCQQFGSS
  67G7			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  65F11			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  65C1	L16	38	EIVLTQSPGTLSLSPGERATLSCRASQTIRNSY
  			LAWYQQQPGQAPRLLIYGAFSRATGIPDRFS
  			GGGSGTDFTLTISRLEPEDFAVYYCQQFGSSL
  			TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  66F6	L15	39	EIVLTQSPGTLSLSPGERATLSCRASQSVRNS
  			YLAWYQQQPGQAPRLLIYGAFSRATGIPDRF
  			SGSGSGTDFTLTISRLEPEDFAVYYCQQFGSS
  			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  64A6	L30	40	EILMTQSPATLSVSPGERATLSCRASQSVNSN
  			LAWYQQKPGQAPRLLIYGTSTRATGVPARF
  			GGSGSGTEFTLTISSLQSEDFAFYYCQQYNT
  			WPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQ
  			LKSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  65F9	L31	41	EILMTQSPATLSVSPGERATLSCRASQSVSSN
  			LAWYQQKPGQSPRLLIYGASTRATGIPARFG
  			GSGSGTDFTLTISSLQSEDFAFYYCQQYNTW
  			PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  64A7	L17	42	EIVLTQSPGTLSLSPGERATLSCRASQSVSRN
  			YLAWYQQKPGQAPRLLIYGASSRATGVPDR
  			FSGSGSGTDFTLTISRLEPEDFAVYYCQQYGS
  			SSLCSFGQGTNLDIRRTVAAPSVFIFPPSDEQL
  			KSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  65C3	L5	43	EMVMTQSPATLSVSPGERATLSCRASQSVSS
  68D5			QLAWYQEKPGRAPRLLIYGASNRAIDIPARL
  			SGSGSGTEFTLTISSLQSEDFAVYYCQQYNN
  			WPWTFGQGTKVEFKRTVAAPSVFIFPPSDEQ
  			LKSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  67F5	L32	44	EIVMTQSPATLSVSPGERVTLSCRASQSVSSN
  			LAWYQQKPGQAPRLLIHGSSNRAIGIPARFS
  			GSGSGTEFTLTISSLQSADFAVYNCQQYEIWP
  			WTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  64B10v1	L33	45	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNN
  64B10v2			YVAWYQQLPGTAPKLLIYDNDKRPSGIPDRF
  			SGSKSGTSATLGITGLQTGDEADYYCGTWDS
  			SLSAVVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  68C8	L34	46	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNN
  			YVSWYQQLPGTAPKLLIYDNNKRPSGIPDRF
  			SGSKSGTSATLGITGLQTGDEADYYCGTWDS
  			SLSAVVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  67A5	L35	47	DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSD
  			DGNTYLDWYLQKPGQSPQLLIYTLSYRASG
  			VPDRFSGTGSGTEFTLKISRVEAEDVGVYYC
  			MQRLEFPITFGQGTRLEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  67C10	L36	48	DFVMTQTPLSLPVTPGEPASISCRSSQSLLNS
  			DDGNTYLDWYLQKPGQSPQLLIYTLSYRAS
  			GVPDRFSGSGSGTDFTLKISRVEAEDVGVYY
  			CMQRIEFPITFGQGTRLEIKRTVAAPSVFIFPP
  			SDEQLKSGTASVVCLLNNFYPREAKVQWKV
  			DNALQSGNSQESVTEQDSKDSTYSLSSTLTL
  			SKADYEKHKVYACEVTHQGLSSPVTKSFNR
  			GEC
  64H6	L37	49	SYELTQPLSVSVALGQTARITCGGNNIGSKN
  			VHWYQQKPGQAPVVVIYRDSKRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYYCQVWDS
  			SPVVFGGGTKLTVLGQPKANPTVTLFPPSSEE
  			LQANKATLVCLISDFYPGAVTVAWKADGSP
  			VKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  63F9	L38	50	DIQMTQSPSSLSVSVGDRVTITCRASQDIRND
  			LAWYQQTPGKAPKRLIYASSSLQSGVPSRFS
  			GTGSGTEFTLTISSLQPEDFATYFCLQRNSYP
  			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  67F6v1	L39	51	DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSD
  			AGTTYLDWYLQKPGQSPQLLIYTLSFRASGV
  			PDRFSGSGSGTDFTLKITRVEAEDVGVYYCM
  			QRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDE
  			QLKSGTASVVCLLNNFYPREAKVQWKVDN
  			ALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
  			ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
  67F6v2	L108	1842	DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSD
  			AGTTYLDWYLQKPGRSPQLLIYTLSFRASGV
  			PDRFSGSGSGTDFTLKITRVEAEDVGVYYCM
  			QRIEFPITFGQGTRLEIKRTVAAPSVFIFPPSDE
  			QLKSGTASVVCLLNNFYPREAKVQWKVDN
  			ALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
  			ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
  48C9	L78	52	DIQMTQSPSSLSASIGDRVTITCRASQNIRTYL
  49A12			NWYQQKPGKAPKLLIYVASSLESGVPSRFSG
  51E2			TGSGTDFALTISSLQPEDFATYYCQQSDSIPR
  			TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  48F3	L77	53	DIQMTQSPSSLSASVGDRVTITCRASQRISSY
  			LNWYQQKPGKAPKFLIYAVSSLQSGVPSRFS
  			GSGSGTDFTLTISSLEPEDFATYYCQQSYSAT
  			FTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  48F8	L49	54	EIVLTQSPDFQSVTPKEKVTITCRASQDIGNS
  53B9			LHWYQQKPDQSPKLLIKFASQSFSGVPSRFS
  56B4			GSGSGTDFALTINSLEAEDAATYYCHQSSDL
  57E7			PLTFGGGTKVDIKRTVAAPSVFIFPPSDEQLK
  57F11			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  48H11	L40	55	DIQMTQSPSSLSTSVGDRVTITCRASQNIRSY
  			LNWYQLKPGKAPKVLIYGASNLQSGVPSRFS
  			GSGSGTDFTLTISNLQSEDFAIYYCQQSYNTP
  			CSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  49A10	L65	56	DIVMTQTPLSLPVTPGEPASISCRSSQSLLDSD
  48D4			DGNTYLDWYLQKPGQSPQLLIYTLSYRASG
  			VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
  			MQRIEFPITFGQGTRLEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  49C8	L45	57	DIQMTQSPSSLSASVGDRVTFTCQASQDINIY
  52H1			LNWYQQKPGKAPKLLIYDVSNLETGVPSRFS
  			GSGSGTDFTFTISSLQPEDIATYFCQQYDNLP
  			FTFGPGTKVDLKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  49G2	L66	58	DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSD
  50C12			DGDTYLDWYLQKPGQSPQLLIYTLSYRASG
  55G11			VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
  			MQHIEFPSTFGQGTRLEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  49G3	L47	59	DIQMTQSPSSLSASIGDRVTITCQASQGISNYL
  			NWYQQKPGKAPKLLIYDASNLETGVPSRFSG
  			SGSGTDFTFTISSLQPEDIATYYCHQYDDLPL
  			TFGGGTKVEIRRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  49H12	L43	60	DIQMTQSPSSLSASVGDRVTITCQASQDITKY
  			LNVVYQQKPGKAPKLLIYDTFILETGVPSRFS
  			GSGSGTDFTFTISSLQPEDIATYYCQQYDNLP
  			LTFGQGTRLEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  51A8	L61	61	NFILTQPHSVSESPGKTVTISCTRSSGSIASDY
  			VQWYQQRPGSSPTTVIYEDKERSSGVPDRFS
  			GSIDSSSNSASLTISGLKTEDEADYYCQSYDR
  			NNHVVFGGGTKLTVLGQPKANPTVTLFPPSS
  			EELQANKATLVCLISDFYPGAVTVAWKADG
  			SPVKAGVETTKPSKQSNNKYAASSYLSLTPE
  			QWKSHRSYSCQVTHEGSTVEKTVAPTECS
  51C10.1	L55	62	SYELTQPPSVSVSPGQTARITCSGDALPKKYA
  			YWYQQKSGQAPVLVIYEDSKRPSGIPERFSG
  			SISGTMATLTISGAQVEDEADYYCYSTDSSV
  			NHVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  51C10.2	L70	63	SYDLTQPPSVSVSPGQTASITCSGDELGDKY
  			ACWYQQKPGQSPVLVIYQDTKRPSGIPERFS
  			GSNSGNTATLTISGTQAMDEADYYCQAWDS
  			GTVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  51E5	L79	64	DIQMTQSPSSLSASVGDRVTITCRASQDIRND
  			LGWYQQKPGKAPNRLIYAASSLQFGVPSRFS
  			GSGSGTEFTLTISSLQPEDFATYYCLQHSSYP
  			LTFGGGTRVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  51G2	L51	65	DIQMTQSPSSVSASVGDRVTITCRASQGISSW
  			LAWYQQKPGKAPKLLIYDASSLQSGVPSRFS
  			GSGSGTDFTLTISSLQPEDFATYYCQQTNSFP
  			PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  52A8	L41	66	DIQMTQSPSFLSASVGDRVTITCRASQTISSY
  			LNWHQQKPGKAPKLLIYAASSLQSGVPSRFS
  			GSGSGTDFSLTISSLQPEDFATYYCQQSYSTP
  			LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  52B8	L82	67	EVVLTQSPATLSVSPGGRATLSCRASQSVSDI
  			LAWYQQKPGQAPRLLIYGASTRATGIPARFS
  			GGGSGTEFTLTISSLQSEDFAVYFCQQYNNW
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  52C1	L67	68	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGINY
  			VSWYQQLPGTAPKLLIYDNNKRPSGIPDRFS
  			GSKSGTSATLGITGLQTGDEADYCCGTWDSS
  			LSAVVFGGGTKLTVLGQPKANPTVTLFPPSS
  			EELQANKATLVCLISDFYPGAVTVAWKADG
  			SPVKAGVETTKPSKQSNNKYAASSYLSLTPE
  			QWKSHRSYSCQVTHEGSTVEKTVAPTECS
  52F8	L42	69	DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN
  			GYNYLDWYLQKPGQSPQLLIYLGSNRASGV
  			PDRFSGRGSGTDFSLKISRVEAEDVGIYYCM
  			QALQTPFTFGPGTNVDIKQTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  52H2	L84	70	ENVLTQSPGTLSLSPGERATLSCRASQSVRSS
  			YLAWYQQRPGQAPRLLIFGASRRATGIPDRF
  			SGSGSGTDFTLTISRLEPEDFAVYYCQQYGSS
  			PRSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  53F6	L63	71	DIVMTQSPLSLPVTPGEPASISCRSSQSLQHSN
  			GYNYLDWYLQKPGQSPQLLIYLDSNRASGV
  			PDRFSGSGSGTDFTLKISRVEAEDIGVYYCM
  			QGLQTPPTFGGGTKVEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  53H5.2	L62	72	DIQMTQSPSSLSASVGDRVTITCRASQGIRND
  			LGWYQQKPGKAPKRLIYAASSLQSGVPSRFS
  			GSGSGTEFTLTISSLQPEDFATYYCLQHKSYP
  			FTFGPGTKMDIKGTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  53H5.3	L80	73	EIVMTQSPVTLSVSPGERAIISCRASQSVSSNV
  			AWYQQKPGQTPRLLIYGASTRATGLPTRFSG
  			SGSGTVFTLTISSLQPEDFAVYYCQQFSNSITF
  			GQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTA
  			SVVCLLNNFYPREAKVQWKVDNALQSGNS
  			QESVTEQDSKDSTYSLSSTLTLSKADYEKHK
  			VYACEVTHQGLSSPVTKSFNRGEC
  54A1	L44	74	DIQMAQSPSSLSASVGDRVTITCQASQDISIY
  55G9			LNWYQLKPGKAPKLLIYDVSNLETGVPSRFS
  			GGGSGTDFTFTISSLQPEDIATYYCQQYDNLP
  			LTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  54H10.1	L53	75	EIVVTQSPGTLSLSVGERAILSCRASQSFSSSY
  55D1			LAWYQQKPGQAPRLLIYGASSRATGIPDRFS
  48H3			GSGSGTDFTLTISRLEPEDFAVYYCQQYGSSR
  53C11			TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  55D3	L71	76	DIQMTQSPSSLSVSVGDRVTITCRASQDISNY
  			LAWFQQKPGKAPKSLIYAASSLQSGVPSKFS
  			GSGSGTDFTLTISSLQPEDFATYYCQQYNIYP
  			RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  55E4	L75	77	DIQMTQSPSSLSTSIGDRITITCRASQSISNYLN
  49B11			WFQQIPGKAPRLLIYTASSLQSGVPSRFSGSG
  50H10			SGTDFTLTISSLQPEDFATYYCQQSSSIPWTF
  53C1			GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
  			SVVCLLNNFYPREAKVQWKVDNALQSGNS
  			QESVTEQDSKDSTYSLSSTLTLSKADYEKHK
  			VYACEVTHQGLSSPVTKSFNRGEC
  55E9	L68	78	DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSN
  			GFNYLDWYLQKPGQSPQVLIYLGSNRASGV
  			PDRFSGSGSGTDFTLKISRVEAEDVGIYYCM
  			QALQTLITFGQGTRLEIKRTVAAPSVFIFPPSD
  			EQLKSGTASVVCLLNNFYPREAKVQWKVDN
  			ALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
  			ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
  55G5	L83	79	SYELTQPPSVSVSPGQTASITCSGDNLGDKY
  			AFWYQQKPGQSPVLVIYQDNKRPSGIPERFS
  			GSNSGNTATLTISGTQAVDEADYYCQAWDS
  			ATVIFGGGTKLTVLGQPKANPTVTLFPPSSEE
  			LQANKATLVCLISDFYPGAVTVAWKADGSP
  			VKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  56A7	L52	80	DIQMTQSPSSVSASVGDRVTITCRASQDISSW
  56E4			LAWYQQKPGKAPKFLIYDASTLQSGVPSRFS
  			GSGSGADFTLTINNLQPEDFATYYCQQTNSF
  			PPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQL
  			KSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  56C11	L64	81	SYVLTQPPSVSVAPGQAARITCGGNDIGSKS
  			VHWYQQKPGQAPVLVVYDDSDRPSGIPERF
  			SGSKSGNTATLIISRVEAGEEADYYCQVWDS
  			SSDVVFGGGTKLTVLGQPKANPTVTLFPPSS
  			EELQANKATLVCLISDFYPGAVTVAWKADG
  			SPVKAGVETTKPSKQSNNKYAASSYLSLTPE
  			QWKSHRSYSCQVTHEGSTVEKTVAPTECS
  56E7	L86	82	DLQMTQSPSSLSASVGDRVTITCQASQDIKK
  			FLNWYQQKPGKAPNLLIYDASNLETGVPSRF
  			SGSGSGTDFTFTISSLQPEDIATYYCQQYAILP
  			FTFGPGTTVDIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  56G1	L76	83	DIQMTQSPSSLSASVGDRVTITCRASQSISNY
  			LNWFLQIPGKAPKLLIYAASSLQSGVPSRFSG
  			SGSGTDFTLTINSLQPEDFGTYYCQQSSTIPW
  			TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  56G3.3	L81	84	EIVLTQSPGTLSLSPGERATLSCRASQSVSRD
  55B10			YLAWYRQKPGQAPRLLVYGASARATGIPDR
  			FSGSGSGTDFTLTISRLEPEDFAVYYCQQYGR
  			SLFTFGPGTKVDIKRTVAAPSVFIFPPSDEQL
  			KSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  57B12	L72	85	DIQMTQSPSSLSVSVGDRVTITCRASHDISNY
  			LAWFQQKPGKAPKSLIYAASSLQSGVPSKFS
  			GSGSGTDFTLTISSLQPEDFATYYCQQYNTYP
  			RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  57D9	L87	86	EIVLTQSPGTLSLSPGERATLSCRASPSVSSSY
  			LAWYQQKPAQAPRLLIYGASSRATGIPDRFS
  			GSGSGTDFTLTISRLEPEDFAVYYCHQYGTSP
  			CSFGQGTKLEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  59A10	L48	87	DIQMTQSPSSVSASVGDRVTITCRASQGISSW
  49H4			LAWYQQKPGKAPKLLIYGASSLQSGVPSRFS
  			GSGSGTDFTLTISSLQPEDFATYYCQQTNSFP
  			PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  59C9	L50	88	DIQMTQSPSSVSASVGDRVTITCRASQDIDS
  58A5			WLVWYQQKPGKAPNLLIYAASNLQRGVPSR
  57A4			FSGSGSGTDFTLTIASLQPEDFATYYCQQTNS
  57F9			FPPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQ
  			LKSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  59G10.2	L60	89	SYELSQPPSVSVSPGQTVSITCSGDNLGDKYA
  			CWYQQRPGQSPVLVIYQDTKRPSGIPERFSG
  			SNSGNTATLTISGTQAMDEADYYCQAWDSS
  			TTWVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  59G10.3	L54	90	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGDN
  			YVSWYQQFPGTAPKLLIYDNNKRPSGIPDRF
  			SGSKSGTSATLGITGLQTGDEADYYCGTWDS
  			SLSVMVFGGGTKLTVLGQPKANPTVTLFPPS
  			SEELQANKATLVCLISDFYPGAVTVAWKAD
  			GSPVKAGVETTKPSKQSNNKYAASSYLSLTP
  			EQWKSHRSYSCQVTHEGSTVEKTVAPTECS
  60D7	L69	91	DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSD
  			DGDTYLDWYLQKPGQSPQLLIYTLSYRASG
  			VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
  			MQRIEFPLTFGGGTKVEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  60F9	L58	92	EIMLTQSPGTLSLSPGERATLSCRASQRVPSS
  48B4			YIVWYQQKPGQAPRLLIYGSSNRATGIPDRF
  52D6			SGSGSGTDFTLTIGRLEPEDFAVYYCQQYGS
  			SPPWTFGQGTKVAIKRTVAAPSVFIFPPSDEQ
  			LKSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  60G5.2	L46	93	SYELTQPPSVSVSPGQTASITCSGNKLGDKY
  			VCWYQQKPGQSPVLVIYQDSKRPSGIPERFS
  			GSNSGNTATLTISGTQALDEADYYCQAWDS
  			STWVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  61G5	L59	94	EIMLTQSPGTLSLSPGERATLSCRASQRVPSS
  			YLVWYQQKPGQAPRLLIYGASNRATGIPDRF
  			SGSGSGTDFTLTIGRLEPEDFAVYYCQQYGS
  			SPPWTFGQGTKVAIKRTVAAPSVFIFPPSDEQ
  			LKSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  52C5	L73	95	DIQMTQSPSSLSASIGDRVTITCRASQSISNYL
  			NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGS
  			GSGTDFTLTISSLQPEDFAIYYCQQSSSIPWTF
  			GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA
  			SVVCLLNNFYPREAKVQWKVDNALQSGNS
  			QESVTEQDSKDSTYSLSSTLTLSKADYEKHK
  			VYACEVTHQGLSSPVTKSFNRGEC
  61H5	L88	96	EIVLTQSPGTLSLSPGERATLSCRASQSVSRD
  52B9			YLAWYRQKPGQAPRLLIYGASSRATGIPDRF
  			SGSGSGTDFTLTISRLEPEDFAVYYCQQYGRS
  			LFTFGPGTTVDIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  59D10v1	L56	97	SYELTQPPSVSVSPGQTARITCSGDAVPKKY
  			ANWYQQKSGQAPVLVIYEDSKRPSGIPERFS
  			GSSSGTMATLTISGAQVEDEADYYCYSTDSS
  			GNHVVFGGGTKLTVLGQPKANPTVTLFPPSS
  			EELQANKATLVCLISDFYPGAVTVAWKADG
  			SPVKAGVETTKPSKQSNNKYAASSYLSLTPE
  			QWKSHRSYSCQVTHEGSTVEKTVAPTECS
  59D10v2	L57	98	SYELTQPPSVSVSPGQTASITCSGDKLGDKY
  			VCWYQQMPGQSPVLVIHQNNKRPSGIPERFS
  			GSNSGNTATLTISGTQAMDEADYYCQAWDS
  			STAVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  56G3.2	L85	99	ETVMTQSPATLSVSPGERATLSCRARQSVGS
  			NLIWYQQKPGQAPRLLIFGASSRDTGIPARFS
  			GSGSGTEFTLTISSLQSEDFAVYYCQQYNNW
  			PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  68G5	L13	100	SYELTQPLSVSVALGQTARLTCGGNNIGSIN
  			VHWYQQKPGQAPVLVIYRDRNRPSGIPERFS
  			GSNSGNTATLTISRAQAGDEADYYCQLWDS
  			STVVFGGGTKLTVLGQPKANPTVTLFPPSSE
  			ELQANKATLVCLISDFYPGAVTVAWKADGS
  			PVKAGVETTKPSKQSNNKYAASSYLSLTPEQ
  			WKSHRSYSCQVTHEGSTVEKTVAPTECS
  60G5.1	L74	1843	DIQMTQSPSSLSASIGDRVTITCRASQSISNYL
  			NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGS
  			GSGTDFTLTISSLQPEDFATYYCQQSSSIPWT
  			FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
  			ASVVCLLNNFYPREAKVQWKVDNALQSGN
  			SQESVTEQDSKDSTYSLSSTLTLSKADYEKH
  			KVYACEVTHQGLSSPVTKSFNRGEC
  48G4	L89	101	EIVLTQSPGTLSLSPGERATLSCRASQSVASS
  53C3.1			YLVWYQQKPGQAPRLLIYGAFSRATGIPDRF
  			SGSGSGTDFTLTIRRLEPEDFAVYYCQQYGT
  			SPFTFGPGTKVDLKRTVAAPSVFIFPPSDEQL
  			KSGTASVVCLLNNFYPREAKVQWKVDNAL
  			QSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
  			YEKHKVYACEVTHQGLSSPVTKSFNRGEC
  50G1	L90	102	DIVMTQTPLSLPVSPGEPASISCRSSQSLLDSD
  			DGDTYLDWYLQKPGQSPQLLIYTLSYRASG
  			VPDRFSVSGSGTDFTLKISRVEAEDVGVYYC
  			MQRIEFPLTFGGGTKVEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  58C2	L91	103	EIVMTQTPLSLPVTPGEPASISCRSSQSLFDND
  			DGDTYLDWYLQKPGQSPQLLIYTLSYRASG
  			VPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
  			MQRLEFPITFGQGTRLEIKRTVAAPSVFIFPPS
  			DEQLKSGTASVVCLLNNFYPREAKVQWKVD
  			NALQSGNSQESVTEQDSKDSTYSLSSTLTLS
  			KADYEKHKVYACEVTHQGLSSPVTKSFNRG
  			EC
  50D4	L92	104	DIQMTQSPSSLSASVGDRVTITCRASQDISNY
  			LAWYQQKPGKVPTLLIYAASTLLSGVPSRFS
  			GSGSGTDFTLTISSLQPEDVAAYYCQKYYSA
  			PFTFGPGTKVDINRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  50G5v1	L93	105	DIQMTQSPSSLSASVGDRVTITCRASQGIRND
  			LGWYQQKPGKAPNRLIYAASSLQSGVPSRFS
  			GSGSGTEFTLTISSLQPEDFATYYCLQHNSYP
  			RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKS
  			GTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  50G5v2	L94	106	DVVMTQCPLSLPVTLGQPASISCRSSQRLVY
  			SDGNTYLNWVQQRPGQSPRRLIYKVSNWDS
  			GVPDRFSGSGSGTDFTLKISRVEAEDVGVNY
  			CMEGTHWPRDFGQGTRLEIKRTVAAPSVFIF
  			PPSDEQLKSGTASVVCLLNNFYPREAKVQW
  			KVDNALQSGNSQESVTEQDSKDSTYSLSSTL
  			TLSKADYEKHKVYACEVTHQGLSSPVTKSF
  			NRGEC
  51C1	L95	107	DIQMTQSPSSLSASIGDRVTITCRASQSISNYL
  			NWFQQIPGKAPRLLIYAASSLQSGVPSRFSGS
  			GSGTDFTLTISSLQPEDFATYYCQQSSSIPWT
  			FGQGTTVEIKRTVAAPSVFIFPPSDEQLKSGT
  			ASVVCLLNNFYPREAKVQWKVDNALQSGN
  			SQESVTEQDSKDSTYSLSSTLTLSKADYEKH
  			KVYACEVTHQGLSSPVTKSFNRGEC
  53C3.2	L96	108	DIVMTQSPATLSVSPGERATLSCRASQSISSN
  			LAWYQQTPGQAPRLLIYGTSIRASTIPARFSG
  			SGSGTEFTLTISSLQSEDFAIYYCHQYTNWPR
  			TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  54H10.3	L97	109	DIQMTQSPSSLSASVGDRVTITCRASQTISIYL
  			NWYQQKPGKAPKFLIYSASSLQSGVPSRFSG
  			SGSGTDFTLTISSLQPEDFSTYFCQQSYSSPLT
  			FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGT
  			ASVVCLLNNFYPREAKVQWKVDNALQSGN
  			SQESVTEQDSKDSTYSLSSTLTLSKADYEKH
  			KVYACEVTHQGLSSPVTKSFNRGEC
  55A7	L98	110	DIQMTQSPSSLSASVGDRVTITCRASQSISSYL
  			NWYQQKPGKAPKLLIYAASSLQSGVPSRFSG
  			SGSGTDFTLTISSLQPEDFATYYCQQTYSAPF
  			TFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSG
  			TASVVCLLNNFYPREAKVQWKVDNALQSG
  			NSQESVTEQDSKDSTYSLSSTLTLSKADYEK
  			HKVYACEVTHQGLSSPVTKSFNRGEC
  55E6	L99	111	EIVLTQSPGTLSLSPGERATLSCRASQSVSRS
  			HLAWYQQNSGQAPRLLIYGASSRATGIPDRF
  			SGSGSGTDFTLTISRLEPEDFAVYYCQQYGSS
  			PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLK
  			SGTASVVCLLNNFYPREAKVQWKVDNALQS
  			GNSQESVTEQDSKDSTYSLSSTLTLSKADYE
  			KHKVYACEVTHQGLSSPVTKSFNRGEC
  61E1	L100	112	DIQMTQSPSSLSASIRDRVTITCRASQSIGTFL
  			NWYQQKPGTAPKLLIYAASSLQSGVPSRFSG
  			SGSGTDFTLTISSLHPEDFASYYCQQSFSTPLT
  			FGGGTKVEITRTVAAPSVFIFPPSDEQLKSGT
  			ASVVCLLNNFYPREAKVQWKVDNALQSGN
  			SQESVTEQDSKDSTYSLSSTLTLSKADYEKH
  			KVYACEVTHQGLSSPVTKSFNRGEC

• TABLE 1B
  Exemplary Antibody Heavy Chain Sequences

  Contained		SEQ ID
  in Clone	Designation	NO:	Amino Acid Sequence

  63E6	H6	113	QVQLMQSGAEVKKPGASVKVSCKASGYTFTG
  66F7			YYMHWVRQAPGQGLEWMGWMNPNSGATKY
  			AQKFQGRVTMTRDTSISTAYMELSRLRSDDTA
  			VYYCARELGDYPFFDYWGQGTLGIVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  66D4	H17	114	QVQLVQSGAEVKKPGASVKVSCRASGYTFTG
  			YYIHWMRQAPGHGLEWMGWINPPSGATNYA
  			QKFRGRVAVTRDTSISTVYMELSRLRSDDTAV
  			YYCARETGTWNFFDYWGQGTLVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  66B4	H10	115	QVQLVQSGAEVKKPGASVKVSCKASGYTFTG
  			YYLHWVRQAPGQGLEWMGWINPNSGGTDYA
  			QKFQGRVTMTRDTSISTAYMELSRLRSDDTAV
  			YYCVGDAATGRYYFDNWGQGTLVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  65B1	H18	116	QVQLVQSGAEVKRPGASVKVSCKASGYTFTG
  			YFMHWVRQAPGQGLEWMGWINPNSGATNYA
  			QKFHGRVTMTRDTSITTVYMELSRLRSDDTAV
  			YYCTRELGIFNWFDPWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  65B4	H20	117	EVQLVESGGGLVQPGGSLRLSCAASGFAFSSY
  			DMHWVRQATGKGLEWVSTIDTAGDAYYPGSV
  			KGRFTISRENAKTSLYLQMNSLRAGDTAVYYC
  			TRDRSSGRFGDFYGMDVWGQGTAVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  67A4	H19	118	EVQLEESGGGLVQPGGSLRLSCAASGFTFRTYD
  			MHWVRQVTGKGLEWVSAIGIAGDTYYSDSVK
  			GRFTISRENAKNSLYLQMNSLRVGDTAVYYCA
  			RDRSSGRFGDYYGMDVWGQGTTVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  63A10v1	H21	119	EVQLVESGGDLVKPGGSLRLSCAVSGITFSNA
  63A10v2			WMSWVRQAPGKGLEWVGRIKSKTDGGTTDY
  63A10v3			AAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTA
  			VYYCTTDSSGSYYVEDYFDYWGQGTLVTVSS
  			ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF
  			PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
  			SVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
  			ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMI
  			SRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV
  			HNAKTKPREEQFNSTFRVVSVLTVVHQDWLN
  			GKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV
  			YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  65H11v1	H22	120	EVQLVESGGGLVKPGGSLRLSCAASGFTFSNA
  65H11v2			WMSWVRQAPGKGLEWVGRIIGKTDGGTTDYA
  			APVKGRFTISRDDSKNTLYLQMNSLKTEDTAV
  			YYCTSDSSGSYYVEDYFDYWGQGTLVAVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  67G10v1	H9	121	EVQLVESGGGLVKPGGSLRLACAASGITFNNA
  67G10v2			WMSWVRQAPGKGLEWVGRIKSKTDGGTTDY
  			AAPVKGRFTISRDDSKSILYLQMNSLKSEDTAV
  			YYCTTDSSGSYYVEDYFDYWGQGTLVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  64C8	H23	122	QVQLVESGGGVVQPGRSLRLSCVASGFTFSSY
  			GMHWVRQDPGKGLEWVAVISYDGSNKHYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARELLWFGEYGVDHGMDVWGQGTTVTVS
  			SASTKGPSVFPLAPCSRSTSESTAALGCLVKDY
  			FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
  			SSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT
  			VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTL
  			MISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE
  			VHNAKTKPREEQFNSTFRVVSVLTVVHQDWL
  			NGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ
  			VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  63G8v1	H1	123	QAQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  63G8v2			GIHWVRQAPGKGLEWVAVISYDGSNKYYADS
  63G8v3			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  68D3v1			CATTVTKEDYYYYGMDVWGQGTTVTVSSAST
  64A8			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  67B4			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  68D3v2	H95	1844	QAQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAFISYAGSNKYY
  			ADSVKGRFTISRDNSKNTLYLQMSSLRAEDTA
  			VYYCATTVTEEDYYYYGMDVWGQGTTVT
  			VSSASTKGPSVFPLAPCSRSTSESTAALGCLVK
  			DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
  			YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV
  			DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK
  			DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD
  			GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD
  			WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR
  			EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI
  			AVEWESNGQPENNYKTTPPMLDSDGSFFLYSK
  			LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
  			LSLSPGK
  66G2	H11	124	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAGISYDGSNKNYAD
  			SVKGRITISRDNPKNTLYLQMNSLRAEDTAVY
  			YCATTVTKEDYYYYGMDVWGQGTTVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  65D1	H26	125	QVQLVESGGGVVQPGRSLRLSCAASGFTFSYY
  			YIHWVRQAPGKGLEWVALIWYDGSNKDYADS
  			VKGRFTISRDNSKNTLYLHVNSLRAEDTAVYY
  			CAREGTTRRGFDYWGQGTLVTVSSASTKGPSV
  			FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW
  			NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
  			NFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  64H5	H7	126	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVIWDDGSNKYYAD
  			SVKGRFTISRDNSKNTLSLQMNSLRAEDTAVY
  			YCAREYVAEAGFDYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  65D4	H25	127	QEQLVESGGGVVQPGRSLRLSCAVSGFTFSFYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CTRALNWNFFDYWGQGTLVTVSSASTKGPSVF
  			PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN
  			SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN
  			FGTQTYTCNVDHKPSNTKVDKTVERKCCVECP
  			PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV
  			VVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE
  			EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS
  			NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM
  			TKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  			YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
  			FSCSVMHEALHNHYTQKSLSLSPGK
  65E3	H24	128	QVQLVESGGGVVQPGRSLRLSCAASGFTLSNY
  			NMHWVRQAPGKGLEWVAVLWYDGNTKYYA
  			DSVKGRVTISRDNSKNTLYLQMNSLRAEDTAV
  			YYCARDVYGDYFAYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  65G4	H8	129	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVIWDDGSNKYY
  			ADSVKGRFTISRDNSKNTLSLQMNSLRAEDTA
  			VYYCAREYVAEAGFDYWGQGTLVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  68G5	H12	130	QVQLVESGGGVVQPGRSLRLSCTASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYHADS
  			VKGRFTISRDDSKNALYLQMNSLRAEDTAVYY
  			CVRDPGYSYGHFDYWGQGTLVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  67G8	H27	131	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVIWYDGSNKDYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARSAVALYNWFDPWGQGTLVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  65B7v1	H28	132	QVQLQESGPGLVNPSQTLSLTCTVSGGSISSDA
  65B7v2			YYWSWIRQHPGKGLEWIGYIFYSGSTYYNPSL
  			KSRVTISVDTSKNRFSLKLSSVTAADTAVYYCA
  			RESRILYFNGYFQHWGQGTLVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  63B6	H4	133	QVQLQESGPGLVKPSQTLSLTCAVSGGSISSGD
  64D4			YYWSWIRQHPGKGLEWIGYIYYSGTTYYNPSL
  			KSRVTISVDTSKNQFSLKLTSVTAADTAVYYC
  			ARMTTPYWYFGLWGRGTLVTVSSASTKGPSVF
  			PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN
  			SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN
  			FGTQTYTCNVDHKPSNTKVDKTVERKCCVECP
  			PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV
  			VVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE
  			EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS
  			NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM
  			TKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  			YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
  			FSCSVMHEALHNHYTQKSLSLSPGK
  63F5	H13	134	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD
  			YYWTWIRQHPGKDLEWITYIYYSGSAYYNPSL
  			KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA
  			RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFP
  			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  63H11	H3	135	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD
  			YYWTWIRQHPGKGLEWIAYIYYSGSTYYNPSL
  			KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA
  			RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFP
  			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  64E6	H2	136	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD
  65E8			YYWTWIRQHPGKGLEWIAYIYYTGSTYYNPSL
  65F11			KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA
  67G7			RMTTPYWYFDLWGRGTLVTVSSASTKGPSVFP
  			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  65C1	H15	137	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD
  			YYWTWIRQHPGKGLEWIAYIFYSGSTYYNPSL
  			KSRVTISLDTSKNQFSLKLNSVTAADTAVYYC
  			ARMTSPYWYFDLWGRGTLVTVSSASTKGPSVF
  			PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN
  			SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN
  			FGTQTYTCNVDHKPSNTKVDKTVERKCCVECP
  			PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV
  			VVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE
  			EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS
  			NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM
  			TKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  			YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
  			FSCSVMHEALHNHYTQKSLSLSPGK
  66F6	H14	138	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGD
  			YYWTWIRHHPGKGLEWIAYIYYSGSTYYNPSL
  			KSRVTISVDTSKNQFSLKLNSVTAADTAVYYC
  			ARMTTPYWYFDLWGRGTLVTVSSASTKGPSVF
  			PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN
  			SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN
  			FGTQTYTCNVDHKPSNTKVDKTVERKCCVECP
  			PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV
  			VVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE
  			EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS
  			NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM
  			TKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  			YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
  			FSCSVMHEALHNHYTQKSLSLSPGK
  64A6	H29	139	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGG
  			YYWSWIRQRPGKGLEWVGYIYYSGGTHYNPS
  			LKSRVTISIDTSENQFSLKLSSVTAADTAVYYC
  			ARVLHYSDSRGYSYYSDFWGQGTLVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  65F9	H30	140	QVQLQESGPGLVKPSQTLSLTCTLSGGSFSSGD
  			YYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSL
  			KSRVTISIDTSKNQFSLKLTSVTAADTAVYYCA
  			RVLHYYDSSGYSYYFDYWGQGTLVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  64A7	H16	141	QLQLQESGPGLVKPSETLSLTCTVSGGSISSDTS
  			YWGWIRQPPGKGLEWIGNIYYSGTTYFNPSLK
  			SRVSVSVDTSKNQFSLKLSSVTAADTAVFYCA
  			RLRGVYWYFDLWGRGTLVTVSSASTKGPSVFP
  			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  65C3	H5	142	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY
  68D5			WSWIRQPPGKGLEWIGYIYYTGSTNYNPSLKSR
  			VTISVDTSKNQFSLKLSSVTAADTAVYYCARE
  			YYYGSGSYYPWGQGTLVTVSSASTKGPSVFPL
  			APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG
  			ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG
  			TQTYTCNVDHKPSNTKVDKTVERKCCVECPPC
  			PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  67F5	H31	143	QVQLKESGPGLVKPSETLSLTCTVSGGSISSYY
  			WSWIRQPPGKGLEWIGYIYYSGNTNYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCARE
  			YYYGSGSYYPWGQGTLVTVSSASTKGPSVFPL
  			APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG
  			ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG
  			TQTYTCNVDHKPSNTKVDKTVERKCCVECPPC
  			PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  64B10v1	H32	144	QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDY
  			YWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKS
  			RVTISIDTSKNQFSLKLNSVTAADTAVYYCARY
  			SSTWDYYYGVDVWGQGTTVTVSSASTKGPSV
  			FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW
  			NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
  			NFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  64B10v2	H96	1845	QVQLLESGPGLVKPSETLSLTCTVSGGSVSSGD
  			YYWSWIRQPPGKGLEWIGFIYYSGGTNYNPPL
  			KSRVTISIDTSKNQFSLKLSSVTAADTAVYYCA
  			RYSSTWDYYYGVDVWGQGTTVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  68C8	H33	145	QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGD
  			NYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSL
  			KSRVTISLHTSKNQFSLRLSSVTAADTAVYYCG
  			RYRSDWDYYYGMDVWGQGTTVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  67A5	H34	146	EVQLVQSGAEVKKPGESLKISCKGSGYSFTSY
  			WIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF
  			QGQVTISADKSINTAYLQWSSLKASDTAIYFCA
  			RRASRGYRFGLAFAIWGQGTMVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  67C10	H35	147	EVQLVQSGAEVKKPGESLKISCQGSGYSFSSY
  			WIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF
  			QGQVTISADKSINTAYLQWSSLKASDTAIYYCA
  			RRASRGYRYGLAFAIWGQGTMVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  64H6	H36	148	EVQLVQSGAEVKKPGESLKISCKGSGYSFTSY
  			WIGWVRQMPGKGLEWMGIIYPGDSETRYSPSF
  			QGQVTISADKSISTAYLQWNSLKTSDTAMYFC
  			ATVAVSAFNWFDPWGQGTLVTVSSASTKGPSV
  			FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW
  			NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
  			NFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  63F9	H37	149	QVQLKESGPGLVKPSQTLSLTCTVSGGSISSGG
  			YYWNWIRQHPGKGLEWIGYIYDSGSTYYNPSL
  			KSRVTMSVDTSKNQFSLKLSSVTAADTAVYYC
  			ARDVLMVYTKGGYYYYGVDVWGQGTTVTVS
  			SASTKGPSVFPLAPCSRSTSESTAALGCLVKDY
  			FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
  			SSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT
  			VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTL
  			MISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE
  			VHNAKTKPREEQFNSTFRVVSVLTVVHQDWL
  			NGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ
  			VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  67F6v1	H38	150	EVQLVQSGAEVKKPGESLKISCKGSGYSFTGY
  67F6v2			WIGWVRQLPGKGLEWMGIIYPGDSDTRYSPSF
  			QGQVTISVDKSINTAYLQWSSLKASDTAMYYC
  			ARRASRGYSYGHAFDFWGQGTMVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  48C9	H73	151	QVQLQQWGAGLLKPSETLSLTCSVYGGSFSGY
  49A12			YWTWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  51E2			RVTISIDTSKNQFSLKLSSVTAADTAVYYCARE
  			SGNFPFDYWGQGTLVTVSSASTKGPSVFPLAPC
  			SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT
  			SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT
  			YTCNVDHKPSNTKVDKTVERKCCVECPPCPAP
  			PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
  			SHEDPEVQFNWYVDGVEVHNAKTKPREEQFN
  			STFRVVSVLTVVHQDWLNGKEYKCKVSNKGL
  			PAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ
  			VSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
  			PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
  			VMHEALHNHYTQKSLSLSPGK
  48F3	H72	152	QVQLQQWGAGPLKPSETLSLTCAVYGGSISGY
  			YWSWIRQPPGKGLEWIGEITHTGSSNYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR
  			GGILWFGEQAFDIWGQGTMVTVSSASTKGPSV
  			FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW
  			NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
  			NFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  48F8	H48	153	EVQLVESGGGLVKPGGSLRLSCTASGFTFRSYS
  53B9			MNWVRQAPGKGLEWVSSISSSSSYEYYVDSVK
  56B4			GRFTISRDIAKSSLWLQMNSLRAEDTAVYYCA
  57E7			RSLSIAVAASDYWGKGTLVTVSSASTKGPSVFP
  57F11			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  48H11	H39	154	QVQLVQSGAEVKKPGASVKVSCKASGYTFTG
  			YYKHWVRQAPGQGLEWMGWINPNSGATKYA
  			QKFQGRVTMTRDTSISTVYMELSRLRSVDTAL
  			YYCAREVPDGIVVAGSNAFDFWGQGTMVTVS
  			SASTKGPSVFPLAPCSRSTSESTAALGCLVKDY
  			FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
  			SSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT
  			VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTL
  			MISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE
  			VHNAKTKPREEQFNSTFRVVSVLTVVHQDWL
  			NGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ
  			VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  49A10	H62	155	QVHLVESGGGVVQPGRSLRLSCAASGFTFSNY
  48D4			GMHWVRQAPGKGLEWVAIIWYDGSNKNYAD
  			SVKGRFTISRDNSKNTLYLEMNSLRAEDTAVY
  			YCARDQDYDFWSGYPYFYYYGMDVWGQGTT
  			VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV
  			KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
  			LYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV
  			DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK
  			DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD
  			GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD
  			WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR
  			EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI
  			AVEWESNGQPENNYKTTPPMLDSDGSFFLYSK
  			LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
  			LSLSPGK
  49C8	H44	156	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY
  52H1			DIDWVRQATGQGLEWMGWMNPNGGNTGYA
  			QKFQGRVTMTRNTSINTAYMELSSLRSEDTAIY
  			YCARGKEFSRAEFDYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  49G2	H63	157	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY
  50C12			GMRWVRQAPGKGLEWVALIWYDGSNKFYAD
  55G11			SVKGRFTISRDNSKNTLNLQMNSLRAEDTAVY
  			YCARDRYYDFWSGYPYFFYYGLDVWGQGTTV
  			TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK
  			DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
  			YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV
  			DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK
  			DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD
  			GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD
  			WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR
  			EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI
  			AVEWESNGQPENNYKTTPPMLDSDGSFFLYSK
  			LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
  			LSLSPGK
  49G3	H46	158	QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPR
  			MGVSWIRQPPGKALEWLTHIFSNDEKSYSTSLK
  			SRLTISKDTSKSQVVLSMTNMDPVDTATYYCV
  			RVDTLNYHYYGMDVWGQGTTVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  49H12	H42	159	QVQLVQSGAEVKKPGASVKVSCMASGYIFTSY
  			DINWVRQATGQGPEWMGWMNPYSGSTGYAQ
  			NFQGRVTMTRNTSINTAYMELSSLRSEDTAVY
  			YCAKYNWNYGAFDFWGQGTMVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  51A8	H58	160	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVISYDGSNKYYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARADGDYPYYYYYYGMDVWGQGTTVTVS
  			SASTKGPSVFPLAPCSRSTSESTAALGCLVKDY
  			FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
  			SSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKT
  			VERKCCVECPPCPAPPVAGPSVFLFPPKPKDTL
  			MISRTPEVTCVVVDVSHEDPEVQFNWYVDGVE
  			VHNAKTKPREEQFNSTFRVVSVLTVVHQDWL
  			NGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ
  			VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  51C10.2	H67	161	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGG
  			YYWSWIRQHPGKGLEWIGYIYYNGSPYDNPSL
  			KRRVTISIDASKNQFSLKLSSMTAADTAVYYCA
  			RGALYGMDVWGQGTTVTVSSASTKGPSVFPL
  			APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG
  			ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG
  			TQTYTCNVDHKPSNTKVDKTVERKCCVECPPC
  			PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  51E5	H74	162	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGELDHSGSINYNPSLKS
  			RVTISVDTSKNQFSLKLTSVTAADTAVYYCAR
  			VLGSTLDYWGQGTLVTVSSASTKGPSVFPLAP
  			CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL
  			TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ
  			TYTCNVDHKPSNTKVDKTVERKCCVECPPCPA
  			PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD
  			VSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
  			NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG
  			LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
  			QVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
  			TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSC
  			SVMHEALHNHYTQKSLSLSPGK
  51G2	H50	163	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  			MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK
  			GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCA
  			RDTYISGWNYGMDVWGQGTTVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  52A8	H40	164	QVQLVQSGAEVKKPGASVKVSCKASGYTFTG
  			YYLHWVRQAPGQGLEWMGWINPNSAATNYA
  			PKFQGRVTVTRDTSISTAYMELSRLRSDDTAVY
  			YCAREGGTYNWFDPWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  52B8	H77	165	QVQLQESGPGLMKPSETLSLTCTVSGGSISYYY
  			WSWIRQSPGKGLEWIGYIYYSGSTNYNPSLKSR
  			VTMSVDTSKNQFSLKLSSVTAADTAVYYCASG
  			TRAFDIWGQGTMVTVSSASTKGPSVFPLAPCSR
  			STSESTAALGCLVKDYFPEPVTVSWNSGALTSG
  			VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYT
  			CNVDHKPSNTKVDKTVERKCCVECPPCPAPPV
  			AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH
  			EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF
  			RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAP
  			IEKTISKTKGQPREPQVYTLPPSREEMTKNQVS
  			LTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
  			MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV
  			MHEALHNHYTQKSLSLSPGK
  52C1	H64	166	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVIWYDGSNNYYAD
  			SVKGRFTISRDNSKSTLFLQMNSLRAEDTAIYY
  			CARDRAGASPGMDVWGQGTTVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  52F8	H41	167	QVQLVQSGAEVKKPGASVKVSCKASGFTFIGY
  			YTHWVRQAPGQGLEWMGWINPSSGDTKYAQ
  			KFQGRVTLARDTSISTAYMELSRLRSDDTAVY
  			YCANSGWYPSYYYGMDVWGQGTTVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  52H2	H79	168	QVQLQESGPGLVKPSETLSLTCTVSGGSISTYY
  			WSWIRQPPGTGLEWIGYIFYNGNANYSPSLKSR
  			VTFSVDTSKNQFSLKLSSVTAADTAVYFCARET
  			DYGDYARPFEYWGQGTLVTVSSASTKGPSVFP
  			LAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS
  			GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNF
  			GTQTYTCNVDHKPSNTKVDKTVERKCCVECPP
  			CPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  53F6	H60	169	QVQLVESGGGVVQPGRSLRLSCAASGFTFSTY
  			GMHWVRQAPGKGLEWVAVIWYDGSNKYYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARGHYDSSGPRDYWGQGTLVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  53H5.2	H59	170	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGQGLEWVALISYDGSNKYYAD
  			SVKGRFTISRDKSKNTLYLQMNSLRAEDTAVY
  			YCAREANWGYNYYGMDVWGQGTTVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  53H5.3	H75	171	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDY
  			YWNWIRQPPGKGPEWIGEINHSGTTNYNPSLK
  			SRVTISVDTSKNQFSLKLSSVTAADTAVYYCVG
  			ILRYFDWLEYYFDYWGQGTLVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  54A1	H43	172	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY
  55G9			DINWVRQATGQGLEWMGWMNPHSGNTGYAQ
  			KFQGRVTMTRNTSINTAYMELSSLRSEDTAVY
  			YCAKYNWNYGAFDFWGQGTMVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  54H10.1	H52	173	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  55D1			MSWVRQAPGKGLEWVSAISGSGRTTYSADSV
  48H3			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  53C11			AKEQQWLVYFDYWGQGTLVTVSSASTKGPSV
  			FPLAPCSRSTSESTAALGCLVKDYFPEPVTVSW
  			NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
  			NFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  55D3	H68	174	QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGV
  			YYWNWIRQHPGKGLEWIGYLYYSGSTYYNPS
  			LKSRLTISADMSKNQFSLKLSSVTVADTAVYY
  			CARDGITMVRGVTHYYGMDVWGQGTTVTVSS
  			ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF
  			PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
  			SVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
  			ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMI
  			SRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV
  			HNAKTKPREEQFNSTFRVVSVLTVVHQDWLN
  			GKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV
  			YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  55E4	H70	175	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  52C5			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  60G5.1			RVTISLDTSNDQFSLRLTSVTAADTAVYYCARV
  49B11			TGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP
  50H10			CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL
  53C1			TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ
  			TYTCNVDHKPSNTKVDKTVERKCCVECPPCPA
  			PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD
  			VSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
  			NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG
  			LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
  			QVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
  			TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSC
  			SVMHEALHNHYTQKSLSLSPGK
  55E9	H65	176	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSFG
  			MHWVRQAPGKGLEWVALIWYDGDNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARNSGWDYFYYYGMDVWGQGTTVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  55G5	H78	177	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY
  			WSWIRQPAGKGLEWIGRIYISGSTNYNPSLENR
  			VTMSGDTSKNQFSLKLNSVTAADTAVYYCAG
  			SGSYSFDYWGQGTLVTVSSASTKGPSVFPLAPC
  			SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT
  			SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT
  			YTCNVDHKPSNTKVDKTVERKCCVECPPCPAP
  			PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
  			SHEDPEVQFNWYVDGVEVHNAKTKPREEQFN
  			STFRVVSVLTVVHQDWLNGKEYKCKVSNKGL
  			PAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ
  			VSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
  			PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
  			VMHEALHNHYTQKSLSLSPGK
  50G1	H84	178	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GLHWVRQAPGKGLEWVAVIWNDGSNKLYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARDQYYDFWSGYPYYHYYGMDVWGQGTT
  			VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV
  			KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
  			LYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV
  			DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK
  			DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD
  			GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD
  			WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR
  			EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI
  			AVEWESNGQPENNYKTTPPMLDSDGSFFLYSK
  			LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
  			LSLSPGK
  56A7	H51	179	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  56E4			MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK
  			GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCA
  			RDIYSSGWSYGMDVWGQGTTVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  56C11	H61	180	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSY
  			GMHWVRQAPGKGLEWVAVIWYDGSYQFYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCARDHVWRTYRYIFDYWGQGTLVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  56E7	H81	181	EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYW
  			IGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQ
  			GQVTISADTSISTAYLQWSRLKASDTAVYYCA
  			RAQLGIFDYWGQGTLVTVSSASTKGPSVFPLAP
  			CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL
  			TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ
  			TYTCNVDHKPSNTKVDKTVERKCCVECPPCPA
  			PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD
  			VSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
  			NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG
  			LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
  			QVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
  			TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSC
  			SVMHEALHNHYTQKSLSLSPGK
  56G1	H71	182	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  			RVTISLDTSNKQFSLRLTSVTAADTAVYYCARV
  			TGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP
  			CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL
  			TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ
  			TYTCNVDHKPSNTKVDKTVERKCCVECPPCPA
  			PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD
  			VSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
  			NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG
  			LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
  			QVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
  			TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSC
  			SVMHEALHNHYTQKSLSLSPGK
  56G3.3	H76	183	QLQLQESGPGLVKPSETLSLTCTVSGDSISSSSY
  55B10			YWGWIRQPPGKGLEWIGMIYYSGTTYYNPSLK
  			SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR
  			VAAVYWYFDLWGRGTLVTVSSASTKGPSVFPL
  			APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG
  			ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG
  			TQTYTCNVDHKPSNTKVDKTVERKCCVECPPC
  			PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  57B12	H69	184	QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGV
  			YYWSWIRQLPGKGLEWIGYIYYSGSTYYNPSL
  			KSRLTISADTSKNQFSLKLSSVTVADTAVYYCA
  			RDGITMVRGVTHYYGMDVWGQGTTVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  57D9	H82	185	QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS
  			ATWNWIRQSPSRGLEWLGRTYYRSKWYNDYA
  			VSVKSRITINPDTSKNQFSLQLNSVTPEDTAVY
  			YCVGIVVVPAVLFDYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  58C2	H85	186	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY
  			GMHWVRQAPGKGLEWVAVIWNDGNNKYYA
  			DSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
  			YYCARDQNYDFWNGYPYYFYYGMDVWGQG
  			TTVTVSSASTKGPSVFPLAPCSRSTSESTAALGC
  			LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
  			SGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNT
  			KVDKTVERKCCVECPPCPAPPVAGPSVFLFPPK
  			PKDTLMISRTPEVTCVVVDVSHEDPEVQFNWY
  			VDGVEVHNAKTKPREEQFNSTFRVVSVLTVVH
  			QDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQ
  			PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS
  			DIAVEWESNGQPENNYKTTPPMLDSDGSFFLY
  			SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ
  			KSLSLSPGK
  59A10	H47	187	QVQVVESGGGLVKPGGSLRLSCAASGFTFSDS
  49H4			YMSWIRQAPGKGLEWISSISSSGSIVYFADSVK
  			GRFTISRDIAKNSLYLHMNSLRAEDTAVYYCA
  			RETFSSGWFDAFDIWGQGTMVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  59C9	H49	188	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  58A5			MSWVRQAPGKGLEWVSSISSSSTYIYYADSLK
  57A4			GRFTISRDNAKNSLFLQVNSLRAEDSAVYYCA
  57F9			RDRWSSGWNEGFDYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  59G10.2	H57	189	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNY
  			GMHWVRQAPGKGLEWVAITSYGGSNKNYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
  			YCAREAGYSFDYWGQGTLVTVSSASTKGPSVF
  			PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN
  			SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN
  			FGTQTYTCNVDHKPSNTKVDKTVERKCCVECP
  			PCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCV
  			VVDVSHEDPEVQFNWYVDGVEVHNAKTKPRE
  			EQFNSTFRVVSVLTVVHQDWLNGKEYKCKVS
  			NKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM
  			TKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  			YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
  			FSCSVMHEALHNHYTQKSLSLSPGK
  59G10.3	H53	190	EVQLLGSGGGLVQPGGSLRLSCAASGFTFNHY
  			AMSWVRQAPGKGLEWVSAISGSGAGTFYADS
  			MKGRFTISRDNSENTLHLQMNSLRAEDTAIYY
  			CAKDLRIAVAGSFDYWGQGTLVTVSSASTKGP
  			SVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK
  60D7	H66	191	QVQLVESGGGVVQPGRSLRLSCAASGFNFSSY
  			GMHWVRQAPGKGLEWVAVIWYDGSNKYYAD
  			SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVF
  			YCARDQYFDFWSGYPFFYYYGMDVWGQGTT
  			VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV
  			KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
  			LYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKV
  			DKTVERKCCVECPPCPAPPVAGPSVFLFPPKPK
  			DTLMISRTPEVTCVVVDVSHEDPEVQFNWYVD
  			GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQD
  			WLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR
  			EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI
  			AVEWESNGQPENNYKTTPPMLDSDGSFFLYSK
  			LTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
  			LSLSPGK
  60F9	H55	192	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  48B4			MSWVRQAPGKGLEWVSVISDSGGSTYYADSV
  52D6			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			AKDHSSGWYYYGMDVWGQGTTVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  60G5.2	H45	193	QVQLVQSGAEVKTPGASVRVSCKASGYTFTNY
  			GISWVRQAPGQGLEWMGWISAYNGYSNYAQK
  			FQDRVTMTTDTSTSTAYMELRSLRSDDTAVYY
  			CAREEKQLVKDYYYYGMDVWGQGSTVTVSS
  			ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF
  			PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
  			SVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
  			ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMI
  			SRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV
  			HNAKTKPREEQFNSTFRVVSVLTVVHQDWLN
  			GKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV
  			YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  61G5	H56	194	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  			MSWVRQSPGKGLEWVSVISGSGGDTYYADSV
  			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			AKDHTSGWYYYGMDVWGQGTTVTVSSASTK
  			GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
  			VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
  			VPSSNFGTQTYTCNVDHKPSNTKVDKTVERKC
  			CVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP
  			EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAK
  			TKPREEQFNSTFRVVSVLTVVHQDWLNGKEYK
  			CKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS
  			REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ
  			PENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
  			QGNVFSCSVMHEALHNHYTQKSLSLSPGK
  59D10v1	H54	195	EVQLLESGGGLVQPGGSLRLSCAASGFTFRNY
  59D10v2			AMSWVRQAPGKGLEWVSGISGSSAGTYYADS
  51C10.1			VKGRFTISRDNSKNTLFLQMDSLRAEDTAVYY
  			CAQDWSIAVAGTFDYWGQGTLVTVSSASTKG
  			PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV
  			SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
  			SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
  			ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEV
  			TCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
  			PREEQFNSTFRVVSVLTVVHQDWLNGKEYKC
  			KVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSR
  			EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP
  			ENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQ
  			GNVFSCSVMHEALHNHYTQKSLSLSPGK
  56G3.2	H80	196	QVQLQESGPGLVKPSETLSLTCTVSDGSISSYY
  			WNWIRQPAGKGLEWIGRIYTSGSTNYNPSLKS
  			RVTMSVDTSKNQFSLNLTSVTAADTAVYYCAR
  			GPLWFDYWGQGTLVTVSSASTKGPSVFPLAPC
  			SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT
  			SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT
  			YTCNVDHKPSNTKVDKTVERKCCVECPPCPAP
  			PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
  			SHEDPEVQFNWYVDGVEVHNAKTKPREEQFN
  			STFRVVSVLTVVHQDWLNGKEYKCKVSNKGL
  			PAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ
  			VSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
  			PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
  			VMHEALHNHYTQKSLSLSPGK
  48G4	H83	197	QVQLVQSGAEVKKPGASVKVSCKVSGYTLTEL
  53C3.1			SIHWVRQAPGKGLEWMGGFDPEDGETIYAQKF
  			QGRVTMTEDTSTDTAYMELSSLRSEDTAVYYC
  			ATHSGSGRFYYYYYGMDVWGQGTTVTVSSAS
  			TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  61H5	H86	198	QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSY
  52B9			YWGWIRQPPGKGLEWIGSIYYSGTTYYNPSLK
  			SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR
  			VAAVYWYFDLWGRGTLVTVSSASTKGPSVFPL
  			APCSRSTSESTAALGCLVKDYFPEPVTVSWNSG
  			ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG
  			TQTYTCNVDHKPSNTKVDKTVERKCCVECPPC
  			PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV
  			VDVSHEDPEVQFNWYVDGVEVHNAKTKPREE
  			QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSN
  			KGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
  			KNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
  			KTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF
  			SCSVMHEALHNHYTQKSLSLSPGK
  50D4	H87	199	QVQLVQSGAEVKKTGASVKVSCKASGYTFTSH
  			DINWVRQATGHGLEWMGWMNPYSGSTGLAQ
  			RFQDRVTMTRNTSISTAYMELSSLRSEDTAVY
  			YCARDLSSGYYYYGLDVWGQGTTVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  50G5v1	H88	200	QVQLVQSGAEVKKPGASVKVSCKASGYPFIGY
  50G5v2			YMHWVRQAPGQGLEWMGWINPDSGGTNYAQ
  			KFQGRVTMTRDTSITTAYMELSRLRSDDTAVF
  			YCARGGYSYGYEDYYGMDVWGQGTTVTVSS
  			ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF
  			PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
  			SVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
  			ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMI
  			SRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV
  			HNAKTKPREEQFNSTFRVVSVLTVVHQDWLN
  			GKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV
  			YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE
  			WESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
  			DKSRWQQGNVFSCSVMHEALHNHYTQKSLSL
  			SPGK
  51C1	H89	201	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  			RVTISLDTSHDQFSLRLTSVTAADTAVYYCARV
  			TGTDAFDFWGQGTMVTVSSASTKGPSVFPLAP
  			CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL
  			TSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ
  			TYTCNVDHKPSNTKVDKTVERKCCVECPPCPA
  			PPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVD
  			VSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
  			NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKG
  			LPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
  			QVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
  			TPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSC
  			SVMHEALHNHYTQKSLSLSPGK
  53C3.2	H90	202	QVQLQESGPGLVKPSQTLSLTCTVSNGSINSGN
  			YYWSWIRQHPGKGLEWIGYIYHSGSAYYNPSL
  			KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA
  			RTTGASDIWGQGIMVTVSSASTKGPSVFPLAPC
  			SRSTSESTAALGCLVKDYFPEPVTVSWNSGALT
  			SGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT
  			YTCNVDHKPSNTKVDKTVERKCCVECPPCPAP
  			PVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
  			SHEDPEVQFNWYVDGVEVHNAKTKPREEQFN
  			STFRVVSVLTVVHQDWLNGKEYKCKVSNKGL
  			PAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ
  			VSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
  			PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
  			VMHEALHNHYTQKSLSLSPGK
  54H10.3	H91	203	QVQVVQSGTEVKKPGASVKVSCKASGYTFTG
  			YYIHWVRQAPGQGLEWMGWINPNSGGTNYA
  			QKFRGRVTMTRDTSISTAYMELSRLRSDDTAV
  			YYCAREEDYSDHHYFDYWGQGTLVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  55A7	H92	204	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYY
  			WSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSR
  			VTISVDTSKNQFSLRLSSVTAADTAVYYCARGI
  			TGTIDFWGQGTLVTVSSASTKGPSVFPLAPCSR
  			STSESTAALGCLVKDYFPEPVTVSWNSGALTSG
  			VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYT
  			CNVDHKPSNTKVDKTVERKCCVECPPCPAPPV
  			AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH
  			EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF
  			RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAP
  			IEKTISKTKGQPREPQVYTLPPSREEMTKNQVS
  			LTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
  			MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV
  			MHEALHNHYTQKSLSLSPGK
  55E6	H93	205	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYS
  			MNWVRQAPGKGLEWISYISSGSSTIYHADSVK
  			GRFTISRDNAKNSLYLQMNSLRDEDTAVYYCA
  			REGYYDSSGYYYNGMDVWGQGTTVTVSSAST
  			KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP
  			VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
  			VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVER
  			KCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISR
  			TPEVTCVVVDVSHEDPEVQFNWYVDGVEVHN
  			AKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE
  			YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
  			PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
  			GQPENNYKTTPPMLDSDGSFFLYSKLTVDKSR
  			WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  61E1	H94	206	QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS
  			AAWNWIRQSPSRGLEWLGRTYYRSKWYNDY
  			AVSVKSRITITPDTSKNQFSLQLKSVTPEDTAIY
  			YCAREGSWSSFFDYWGQGTLVTVSSASTKGPS
  			VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS
  			WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
  			SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE
  			CPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVT
  			CVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
  			REEQFNSTFRVVSVLTVVHQDWLNGKEYKCK
  			VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSRE
  			EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
  			NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQG
  			NVFSCSVMHEALHNHYTQKSLSLSPGK

• Each of the exemplary heavy chains (H1, H2, H3 etc.) listed in Table 1B, infra, can be combined with any of the exemplary light chains shown in Table 1A, infra, to form an antibody. Examples of such combinations include H1 combined with any of L1 through L100; H2 combined with any of L1 through L100; H3 combined with any of L1 through L100, and so on. In some instances, the antibodies include at least one heavy chain and one light chain from those listed in Tables 1A and 1B, infra; particular examples pairings of light chains and heavy chains include L1 with H1, L2 with H1, L3 with H2 or H3, L4 with H4, L5 with H5, L6 with H6, L7 with H6, L8 with H7 or H8, L9 with H9, L10 with H9, L11 with H10, L12 with H11, L13 with H12, L13 with H14, L14 with H13, L15 with H14, L16 with H15, L17 with H16, L18 with H17, L19 with H18, L20 with H19, L21 with H20, L22 with H21, L23 with H22, L24 with H23, L25 with H24, L26 with H25, L27 with H26, L28 with H27, L29 with H28, L30 with H29, L31 with H30, L32 with H31, L33 with H32, L34 with H33, L35 with H34, L36 with H35, L37 with H36, L38 with H37, L39 with H38, L40 with H39, L41 with H40, L42 with H41, L43 with H42, L44 with H43, L45 with H44, L46 with H45, L47 with H46, L48 with H47, L49 with H48, L50 with H49, L51 with H50, L52 with H51, L53 with H52, L54 with H53, L55 with H54, and L56 with H54, L57 with H54, L58 with H55, L59 with H56, L60 with H57, L61 with H58, L62 with H59, L63 with H60, L64 with H1, L65 with H62, L66 with H63, L67 with H64, L68 with H65, L69 with H66, L70 with H67, L71 with H68, L72 with H69, L73 with H70, L74 with H70, and L75 with H70, L76 with H71, L77 with H72, L78 with H73, L79 with H74, L80 with H75, L81 with H76, L82 with H77, L83 with H78, L84 with H79, L85 with H80, L86 with H81, L87 with H82, L88 with H86, L89 with H83, L90 with H84, L91 with H85, L92 with H87, L93 with H88, L94 with H88, L95 with H89, L96 with H90, L97 with H91, L98 with H92, L99 with H93, and L100 with H94. In addition to antigen binding proteins comprising a heavy and a light chain from the same clone, a heavy chain from a first clone can be paired with a light chain from a second clone (e.g., a heavy chain from a first clone paired with a light chain from a second clone or a heavy chain from a first clone paired with a light chain from a second clone). Generally, such pairings can include V_L with 90% or greater homology can be paired with the heavy chain of the naturally occurring clone.
• In some instances, the antibodies comprise two different heavy chains and two different light chains listed in Tables 1A and 1B, infra. In other instances, the antibodies contain two identical light chains and two identical heavy chains. As an example, an antibody or immunologically functional fragment can include two L1 light chains with two H1 heavy chains, two L2 light chains with two H1 heavy chains, two L3 light chains with two H2 heavy chains or two H3 heavy chains, two L4 light chains with two H4 heavy chains, two L5 light chains with two H5 heavy chains, two L6 light chains with two H6 heavy chains, two L7 light chains with two H6 heavy chains, two L8 light chains with two H7 heavy chains or two H8 heavy chains, two L9 light chains with two H9 heavy chains, two L10 light chains with two H9 heavy chains, two L11 light chains with two H10 heavy chains, two L12 light chains with two H11 heavy chains, two L13 light chains with two H12 heavy chains, two L13 light chains with two H14 heavy chains, two L14 light chains with two H13 heavy chains, two L15 light chains with two H14 heavy chains, two L16 light chains with two H15 heavy chains, two L17 light chains with two H16 heavy chains, two L18 light chains with two H17 heavy chains, two L19 light chains with two H18 heavy chains, two L20 light chains with two H19 heavy chains, two L21 light chains with two H20 heavy chains, two L22 light chains with two H21 heavy chains, two L23 light chains with two H22 heavy chains, two L24 light chains with two H23 heavy chains, two L25 light chains with two H24 heavy chains, two L26 light chains with two H25 heavy chains, two L27 light chains with two H26 heavy chains, two L28 light chains with two H27 heavy chains, two L29 light chains with two H28 heavy chains, two L30 light chains with two H29 heavy chains, two L31 light chains with two H30 heavy chains, two L32 light chains with two H31 heavy chains, two L33 light chains with two H32 heavy chains, two L34 light chains with two H33 heavy chains, two L35 chains with two H34 heavy chains, two L36 chains with two H35 heavy chains, two L37 light chains with two H36 heavy chains, two L38 light chains with two H37 heavy chains, two L39 light chains with two H38 heavy chains, two L40 light chains with two H39 heavy chains, two L41 light chains with two H40 heavy chains, two L42 light chains with two H41 heavy chains, two L43 light chains with two H42 heavy chains, two L44 light chains with two H43 heavy chains, two L45 light chains with two H44 heavy chains, two L46 light chains with two H45 heavy chains, two L47 light chains with two H46 heavy chains, two L48 light chains with two H47 heavy chains, two L49 light chains with two H48 heavy chains, two L50 light chains with two H49 heavy chains, two L51 light chains with two H50 heavy chains, two L52 light chains with two H51 heavy chains, two L53 light chains with two H52 heavy chains, two L54 light chains with two H53 heavy chains, two L55 light chains with two H54 heavy chains, and two L56 light chains with two H54 heavy chains, two L57 light chains with two H54 heavy chains, two L58 light chains with two H55 heavy chains, two L59 light chains with two H56 heavy chains, two L60 light chains with two H57 heavy chains, two L61 light chains with two H58 heavy chains, two L62 light chains with two H59 heavy chains, two L63 light chains with two H60 heavy chains, two L64 light chains with two H1 heavy chains, two L65 light chains with two H62 heavy chains, two L66 light chains with two H63 heavy chains, two L67 light chains with two H64 heavy chains, two L68 light chains with two H65 heavy chains, two L69 light chains with two H66 heavy chains, two L70 light chains with two H67 heavy chains, two L71 light chains with two H68 heavy chains, two L72 light chains with two H69 heavy chains, two L73 light chains with two H70 heavy chains, two L74 light chains with two H70 heavy chains, and two L75 light chains with two H70 heavy chains, two L76 light chains with two H71 heavy chains, two L77 light chains with two H72 heavy chains, two L78 light chains with two H73 heavy chains, two L79 light chains with two H74 heavy chains, two L80 light chains with two H75 heavy chains, two L81 light chains with two H76 heavy chains, two L82 light chains with two H77 heavy chains, two L83 light chains with two H78 heavy chains, two L84 light chains with two H79 heavy chains, two L85 light chains with two H80 heavy chains, two L86 light chains with two H81 heavy chains, two L87 light chains with two H82 heavy chains, two L88 light chains with two H86 heavy chains, two L89 light chains with two H83 heavy chains, two L90 light chains with two H84 heavy chains, two L91 light chains with two H85 heavy chains, two L92 light chains with two H87 heavy chains, two L93 light chains with two H88 heavy chains, two L94 light chains with two H88 heavy chains, two L95 light chains with two H89 heavy chains, two L96 light chains with two H90 heavy chains, two L97 light chains with two H91 heavy chains, two L98 light chains with two H92 heavy chains, two L99 light chains with two H93 heavy chains, and two L100 light chains with two H94 heavy chains, as well as other similar combinations of pairs comprising the light chains and pairs of heavy chains as listed in Tables 1A and 1B, infra.
• In another aspect of the instant disclosure, “hemibodies” are provided. A hemibody is a monovalent antigen binding protein comprising (i) an intact light chain, and (ii) a heavy chain fused to an Fc region (e.g., an IgG2 Fc region of SEQ ID NO: 11), optionally via a linker, The linker can be a (G4S)_x linker (SEQ ID NO: 207) where “x” is a non-zero integer (e.g., (G4S)₂, (G4S)₃, (G4S)₄, (G4S)₅, (G4S)₆, (G4S)₇, (G4S)₈, (G4S)₉, (G4S)₁₀; SEQ ID NOs: 208-216, respectively). Hemibodies can be constructed using the provided heavy and light chain components.
• Other antigen binding proteins that are provided are variants of antibodies formed by combination of the heavy and light chains shown in Tables 1A and 1B, infra and comprise light and/or heavy chains that each have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences of these chains. In some instances, such antibodies include at least one heavy chain and one light chain, whereas in other instances the variant forms contain two identical light chains and two identical heavy chains.
Variable Domains of Antigen Binding Proteins
• Also provided are antigen binding proteins that contain an antibody heavy chain variable region selected from the group consisting of V _H1, V _H2, V _H3, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94 as shown in Table 2B and/or an antibody light chain variable region selected from the group consisting of V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100 as shown in Table 2A, and immunologically functional fragments, derivatives, muteins and variants of these light chain and heavy chain variable regions.

• TABLE 2A
  Exemplary Antibody Variable Light (VL) Chains

  Contained		SEQ ID
  in Clone	Designation	NO.	Amino Acid Sequence

  63E6	V L6	217	DIQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWY
  			QQKPGKAPNLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISGLQPEDFSTYYCQQSYSTSLTFGGGTKVEIKR
  66F7	V L7	218	DIQMTQSPSSLSASVGDRVTITCRTSQSISNYLNWY
  			QQKPGKAPNLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISGLQPEDFSTYYCQQSYSTSLTFGGGTKVEIKR
  66D4	VL18	219	DIQMTQSPSSLSASVGDRITITCRASQIISRYLNWY
  			QQNPGKAPKLLISAASSLQSGVPSRFSGSGSGPDFT
  			LTISSLQPEDFTTYYCQQSYSSPLTFGGGTKVEVKR
  66B4	V L11	220	DIQMTQSPSSVSSSVGDRVTITCRASQGISRWLAW
  			YQQKPGKAPKLLIYAASSLKSGVPSRFSGSGSGTD
  			FTLTISSLQPEDFATYYCQQANSFPPTFGQGTKVEI
  			KR
  65B1	VL19	221	DIQMTQSPSSLSASVGDRVTITCRASQNINNYLNW
  			YRQKPGKAPELLIYTTSSLQSGVPSRFSGSGSGTDF
  			TLTISSLETEDFETYYCQQSYSTPLTFGGGTKVEIKR
  65B4	VL21	222	SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVQWY
  			QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTA
  			SLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTK
  			LTVLG
  67A4	V L20	223	SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWY
  			QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTA
  			TLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTK
  			LTVLG
  63A10v1	VL22	224	SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW
  			YQQKPGQDPVLVIYCDSNRPSGIPER
  			FSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSD
  			GVFGGGTKLTVLG
  63A10v2	VL101	1846	SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW
  			YQQKPGQDPVLVIYCDSNRPSGIPER
  			FSGSNPGNTATLTISRIEAGDEADYYCQAWDSTTV
  			VFGGGTKLTVLG
  63A10v3	VL102	1847	SYELTQPPSVSVSPGQTANITCSGDKLGNRYTCWY
  			QQKSGQSPVLVIYQDSERPSGIPER
  			FSGSNSGNTATLTISGTQAMDEADYYCQAWDSTT
  			VVFGGGTKLTVLG
  65H11v1	V L23	225	SYELTQPHSVSVATAQMARITCGGNNIGSKTVHW
  			FQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTA
  			TLTISRIEAGDEADYYCQVWDSSCDGVFGGGTKLT
  			VLG
  65H11v2	VL103	1848	SYELTQPPSVSVSPGQTANITCSGDKLGDRYVCWY
  			QQKPGQSPVLVIYQDSKRPSGIPEQFSGSNSGNTAT
  			LTISGTQAIDEADYYCQAWDSITVVFGGGTKLTVLG
  67G10v1	V L9	226	SYELTQPHSVSVATAQMARITCGGNNIGSKAVHW
  			YQQKPGQDPVLVIYSDSNRPSGIPERFSGSNPGNTA
  			TLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLT
  			VLG
  67G10v2	V L10	227	SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWY
  			QQKPGQSPVLVIYQDNERPSGIPERFSGSNSGNTAT
  			LTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTV
  			LG
  64C8	V L24	228	DVVMTQSPLSLPVTLGQPASISRRSSPSLVYSDGNT
  			YLNCFQQRPGHSPRRLIYKGSNWDSGVPDRFSGSG
  			SGTDFTLKISRVEAEDVGIYYCIQDTHWPTCSFGQ
  			GTKLEIKR
  64A8	V L1	229	DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW
  67B4			YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE
  			FTLTISTLQPEDFATYSCLQHNSYPLTFGGGTKVEI
  			KR
  63G8v1	VL104	1849	DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW
  			YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE
  			FTLTISTLQPDDFATYSCLQHNSYPLTFGGGTKVEI
  			KR
  63G8v2	VL105	1850	DIQMTQSPSSLSASVGDRVTITCRASQGIRSGLGW
  			YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE
  			FTLTVSSLQPEDFATYSCLQHNSYPLTFGGGTKVEI
  			KR
  63G8v3	VL106	1851	DIQMTQSPSSLSASVGDRVTITCRASQGIRSGLGW
  			YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE
  			FTLTVSSLQPEDFATYSCLQHNTYPLTFGGGTKGEI
  			RR
  66G2	V L12	230	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW
  			YQQKPGKAPKRLIYAASNLQSGVPSRFSGSGSGTK
  			FTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEI
  			KR
  68D3v1	V L2	231	DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW
  68D3v2			YQQKPGKAPKRLIYAASNLQRGVPSRFSGSGSGTE
  			FTLTISTLQPDDFATYSCLQHNSYPLTFGGGTKVEI
  			KR
  65D1	V L27	232	SYDLTQPPSVSVSPGQTASITCSGDKLGDKYVCWY
  			QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTAT
  			LTISGIQAMDEADYYCQAWDSRVFGGGTKLTVLG
  64H5	V L8	233	SYEMTQPLSVSVALGQTARITCGGNNIGSKNVHW
  65G4			YQQKPGQAPVLVIYRDSKRPSGIPERFSGSNSGNT
  			ATLTISRAQAGDEADYYCQVWDSSSVVFGGGTKL
  			TVLG
  65D4	V L26	234	SYELTQPLSVSVALGQTARIPCGGNDIGSKNVHWY
  			QQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA
  			TLTISRAQAGDEADYYCQVWDSNPVVFGGGTKLT
  			VLG
  65E3	V L25	235	SYELTQPLSVSVALGQTARITCGGNNIGSKNVHWY
  			QQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA
  			TLTISRAQAGDEADYYCQVWDSSTVVFGGGTKLT
  			VLG
  68G5	V L13	236	SYELTQPLSVSVALGQTARLTCGGNNIGSINVHWY
  			QQKPGQAPVLVIYRDRNRPSGIPERFSGSNSGNTA
  			TLTISRAQAGDEADYYCQLWDSSTVVFGGGTKLT
  			VLG
  67G8	VL28	237	SYELTQPLSVSVALGQTARITCGGNNIGSYNVFWY
  			QQKPGQAPVLVIYRDSKRPSGIPERFSGSNSGNTAT
  			LTISRAQAGDEADYHCQVWDSSTVVFGGGTKLTV
  			LG
  65B7v1	VL29	238	EIVLTQSPGTLSLSPGERATLSCRASQSVSSIYLAW
  			YQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCQQYGSSCSFGQGTKLEIKR
  65B7v2	VL107	1852	DVVMTQSPLSLPVTLGQPASISYRSSQSLVYSDGD
  			TYLNWFQQRPGQSPRRLIYKVSNWDSGVPDRFSG
  			SGSGTDFTLKISRVEAEDVGVYYCMQGTHWRGW
  			TFGQGTKVEIKR
  63B6	V L4	239	EIVLTQSPGTLSLSPGERATLSCRASQSVSNSYLAW
  64D4			YQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCQQFGRSFTFGGGTKVEIRR
  63F5	V L14	240	EVVLTQSPGTLSLSPGERATLSCRASQTVRNNYLA
  			WYQQQPGQAPRLLIFGASSRATGIPDRFSGSGSGT
  			DFTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEI
  			KR
  65E8	V L3	241	EIVLTQSPGTLSLSPGERATLSCRASQSVRNSYLAW
  63H11			YQQQPGQAPRLLIYGAFSRASGIPDRFSGSGSGTDF
  64E6			TLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR
  65F11
  67G7
  65C1	V L16	242	EIVLTQSPGTLSLSPGERATLSCRASQTIRNSYLAW
  			YQQQPGQAPRLLIYGAFSRATGIPDRFSGGGSGTD
  			FTLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR
  66F6	V L15	243	EIVLTQSPGTLSLSPGERATLSCRASQSVRNSYLAW
  			YQQQPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCQQFGSSLTFGGGTKVEIKR
  64A6	V L30	244	EILMTQSPATLSVSPGERATLSCRASQSVNSNLAW
  			YQQKPGQAPRLLIYGTSTRATGVPARFGGSGSGTE
  			FTLTISSLQSEDFAFYYCQQYNTWPWTFGQGTKVE
  			IKR
  65F9	V L31	245	EILMTQSPATLSVSPGERATLSCRASQSVSSNLAW
  			YQQKPGQSPRLLIYGASTRATGIPARFGGSGSGTDF
  			TLTISSLQSEDFAFYYCQQYNTWPWTFGQGTKVEI
  			KR
  64A7	V L17	246	EIVLTQSPGTLSLSPGERATLSCRASQSVSRNYLAW
  			YQQKPGQAPRLLIYGASSRATGVPDRFSGSGSGTD
  			FTLTISRLEPEDFAVYYCQQYGSSSLCSFGQGTNLD
  			IRR
  65C3	V L5	247	EMVMTQSPATLSVSPGERATLSCRASQSVSSQLA
  68D5			WYQEKPGRAPRLLIYGASNRAIDIPARLSGSGSGTE
  			FTLTISSLQSEDFAVYYCQQYNNWPWTFGQGTKV
  			EFKR
  67F5	VL32	248	EIVMTQSPATLSVSPGERVTLSCRASQSVSSNLAW
  			YQQKPGQAPRLLIHGSSNRAIGIPARFSGSGSGTEF
  			TLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEI
  			KR
  64B10v1	VL33	249	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVA
  64B10v2			WYQQLPGTAPKLLIYDNDKRPSGIPDRFSGSKSGT
  			SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGG
  			TKLTVLG
  68C8	VL34	250	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS
  			WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT
  			SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGG
  			TKLTVLG
  67A5	VL35	251	DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGN
  			TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGT
  			GSGTEFTLKISRVEAEDVGVYYCMQRLEFPITFGQ
  			GTRLEIKR
  67C10	VL36	252	DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGN
  			TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS
  			GSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQ
  			GTRLEIKR
  64H6	VL37	253	SYELTQPLSVSVALGQTARITCGGNNIGSKNVHWY
  			QQKPGQAPVVVIYRDSKRPSGIPERFSGSNSGNTA
  			TLTISRAQAGDEADYYCQVWDSSPVVFGGGTKLT
  			VLG
  63F9	V L38	254	DIQMTQSPSSLSVSVGDRVTITCRASQDIRNDLAW
  			YQQTPGKAPKRLIYASSSLQSGVPSRFSGTGSGTEF
  			TLTISSLQPEDFATYFCLQRNSYPLTFGGGTKVEIKR
  67F6v1	VL39	255	DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSDAGTT
  			YLDWYLQKPGQSPQLLIYTLSFRASGVPDRFSGSG
  			SGTDFTLKITRVEAEDVGVYYCMQRIEFPITFGQGT
  			RLEIKR
  67F6v2	VL108	1853	DIVMTQTPLSLPVIPGEPASIFCRSSQSLLNSDAGTT
  			YLDWYLQKPGRSPQLLIYTLSFRASGVPDRFSGSG
  			SGTDFTLKITRVEAEDVGVYYCMQRIEFPITFGQGT
  			RLEIKR
  48C9	VL78	256	DIQMTQSPSSLSASIGDRVTITCRASQNIRTYLNWY
  49A12			QQKPGKAPKLLIYVASSLESGVPSRFSGTGSGTDF
  51E2			ALTISSLQPEDFATYYCQQSDSIPRTFGQGTKVEIKR
  48F3	VL77	257	DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWY
  			QQKPGKAPKFLIYAVSSLQSGVPSRFSGSGSGTDFT
  			LTISSLEPEDFATYYCQQSYSATFTFGPGTKVDIKR
  48F8	VL49	258	EIVLTQSPDFQSVTPKEKVTITCRASQDIGNSLHWY
  53B9			QQKPDQSPKLLIKFASQSFSGVPSRFSGSGSGTDFA
  56B4			LTINSLEAEDAATYYCHQSSDLPLTFGGGTKVDIKR
  57E7
  57F11
  48H11	V L40	259	DIQMTQSPSSLSTSVGDRVTITCRASQNIRSYLNWY
  			QLKPGKAPKVLIYGASNLQSGVPSRFSGSGSGTDF
  			TLTISNLQSEDFAIYYCQQSYNTPCSFGQGTKLEIKR
  49A10	V L65	260	DIVMTQTPLSLPVTPGEPASISCRSSQSLLDSDDGN
  48D4			TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS
  			GSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQ
  			GTRLEIKR
  49C8	VL45	261	DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNW
  52H1			YQQKPGKAPKLLIYDVSNLETGVPSRFSGSGSGTD
  			FTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDL
  			KR
  49G2	V L66	262	DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDT
  50C12			YLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSG
  55G11			SGTDFTLKISRVEAEDVGVYYCMQHIEFPSTFGQG
  			TRLEIKR
  49G3	VL47	263	DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWY
  			QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDF
  			TFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR
  49H12	V L43	264	DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNW
  			YQQKPGKAPKLLIYDTFILETGVPSRFSGSGSGTDF
  			TFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR
  51A8	VL61	265	NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQW
  			YQQRPGSSPTTVIYEDKERSSGVPDRFSGSIDSSSNS
  			ASLTISGLKTEDEADYYCQSYDRNNHVVFGGGTK
  			LTVLG
  51C10.1	VL55	266	SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWY
  			QQKSGQAPVLVIYEDSKRPSGIPERFSGSISGTMAT
  			LTISGAQVEDEADYYCYSTDSSVNHVVFGGGTKL
  			TVLG
  51C10.2	V L70	267	SYDLTQPPSVSVSPGQTASITCSGDELGDKYACWY
  			QQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTAT
  			LTISGTQAMDEADYYCQAWDSGTVVFGGGTKLT
  			VLG
  51E5	VL79	268	DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGW
  			YQQKPGKAPNRLIYAASSLQFGVPSRFSGSGSGTE
  			FTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEI
  			KR
  51G2	VL51	269	DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAW
  			YQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD
  			FTLTISSLQPEDFATYYCQQTNSFPPWTFGQGTKVE
  			IKR
  52A8	VL41	270	DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWH
  			QQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFS
  			LTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR
  52B8	VL82	271	EVVLTQSPATLSVSPGGRATLSCRASQSVSDILAW
  			YQQKPGQAPRLLIYGASTRATGIPARFSGGGSGTE
  			FTLTISSLQSEDFAVYFCQQYNNWPLTFGGGTKVE
  			IKR
  52C1	VL67	272	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGINYVSW
  			YQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSA
  			TLGITGLQTGDEADYCCGTWDSSLSAVVFGGGTK
  			LTVLG
  52F8	VL42	273	DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYN
  			YLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGR
  			GSGTDFSLKISRVEAEDVGIYYCMQALQTPFTFGP
  			GTNVDIKQ
  52H2	VL84	274	ENVLTQSPGTLSLSPGERATLSCRASQSVRSSYLA
  			WYQQRPGQAPRLLIFGASRRATGIPDRFSGSGSGT
  			DFTLTISRLEPEDFAVYYCQQYGSSPRSFGQGTKLE
  			IKR
  53F6	VL63	275	DIVMTQSPLSLPVTPGEPASISCRSSQSLQHSNGYN
  			YLDWYLQKPGQSPQLLIYLDSNRASGVPDRFSGSG
  			SGTDFTLKISRVEAEDIGVYYCMQGLQTPPTFGGG
  			TKVEIKR
  53H5.2	VL62	276	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW
  			YQQKPGKAPKRLIYAASSLQSGVPSRFSGSGSGTE
  			FTLTISSLQPEDFATYYCLQHKSYPFTFGPGTKMDI
  			KG
  53H5.3	V L80	277	EIVMTQSPVTLSVSPGERAIISCRASQSVSSNVAWY
  			QQKPGQTPRLLIYGASTRATGLPTRFSGSGSGTVFT
  			LTISSLQPEDFAVYYCQQFSNSITFGQGTRLEIKR
  54A1	VL44	278	DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWY
  55G9			QLKPGKAPKLLIYDVSNLETGVPSRFSGGGSGTDF
  			TFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR
  54H10.1	V L53	279	EIVVTQSPGTLSLSVGERAILSCRASQSFSSSYLAW
  55D1			YQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDF
  48H3			TLTISRLEPEDFAVYYCQQYGSSRTFGQGTKVEIKR
  53C11
  55D3	V L71	280	DIQMTQSPSSLSVSVGDRVTITCRASQDISNYLAWF
  			QQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFT
  			LTISSLQPEDFATYYCQQYNIYPRTFGQGTKVEIKR
  55E4	VL75	281	DIQMTQSPSSLSTSIGDRITITCRASQSISNYLNWFQ
  49B11			QIPGKAPRLLIYTASSLQSGVPSRFSGSGSGTDFTLT
  50H10			ISSLQPEDFATYYCQQSSSIPWTFGQGTKVEIKR
  53C1
  55E9	VL68	282	DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGFN
  			YLDWYLQKPGQSPQVLIYLGSNRASGVPDRFSGS
  			GSGTDFTLKISRVEAEDVGIYYCMQALQTLITFGQ
  			GTRLEIKR
  55G5	VL83	283	SYELTQPPSVSVSPGQTASITCSGDNLGDKYAFWY
  			QQKPGQSPVLIYQDNKRPSGIPERFSGSNSGNTAT
  			LTISGTQAVDEADYYCQAWDSATVIFGGGTKLTV
  			LG
  56A7	V L52	284	DIQMTQSPSSVSASVGDRVTITCRASQDISSWLAW
  56E4			YQQKPGKAPKFLIYDASTLQSGVPSRFSGSGSGAD
  			FTLTINNLQPEDFATYYCQQTNSFPPWTFGQGTKV
  			EIKR
  56C11	V L64	285	SYVLTQPPSVSVAPGQAARITCGGNDIGSKSVHWY
  			QQKPGQAPVLVVYDDSDRPSGIPERFSGSKSGNTA
  			TLIISRVEAGEEADYYCQVWDSSSDVVFGGGTKLT
  			VLG
  56E7	VL86	286	DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNW
  			YQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTD
  			FTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR
  56G1	VL76	287	DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWF
  			LQIPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTINSLQPEDFGTYYCQQSSTIPWTFGQGTKVEIKR
  56G3.3	V L81	288	EIVLTQSPGTLSLSPGERATLSCRASQSVSRDYLAW
  55B10			YRQKPGQAPRLLVYGASARATGIPDRFSGSGSGTD
  			FTLTISRLEPEDFAVYYCQQYGRSLFTFGPGTKVDI
  			KR
  57B12	V L72	289	DIQMTQSPSSLSVSVGDRVTITCRASHDISNYLAWF
  			QQKPGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFT
  			LTISSLQPEDFATYYCQQYNTYPRTFGQGTKVEIKR
  57D9	VL87	290	EIVLTQSPGTLSLSPGERATLSCRASPSVSSSYLAW
  			YQQKPAQAPRLLIYGASSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCHQYGTSPCSFGQGTKLEIKR
  59A10	VL48	291	DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAW
  49H4			YQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTD
  			FTLTISSLQPEDFATYYCQQTNSFPPWTFGQGTKVE
  			IKR
  59C9	V L50	292	DIQMTQSPSSVSASVGDRVTITCRASQDIDSWLVW
  58A5			YQQKPGKAPNLLIYAASNLQRGVPSRFSGSGSGTD
  57A4			FTLTIASLQPEDFATYYCQQTNSFPPWTFGQGTKV
  57F9			EIKR
  59G10.2	V L60	293	SYELSQPPSVSVSPGQTVSITCSGDNLGDKYACWY
  			QQRPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTAT
  			LTISGTQAMDEADYYCQAWDSSTTWVFGGGTKL
  			TVLG
  59G10.3	VL54	294	QSVLTQPPSVSAAPGQKVTISCSGSSSNIGDNYVS
  			WYQQFPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT
  			SATLGITGLQTGDEADYYCGTWDSSLSVMVFGGG
  			TKLTVLG
  60D7	VL69	295	DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDT
  			YLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGSG
  			SGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGG
  			TKVEIKR
  60F9	VL58	296	EIMLTQSPGTLSLSPGERATLSCRASQRVPSSYIVW
  48B4			YQQKPGQAPRLLIYGSSNRATGIPDRFSGSGSGTDF
  52D6			TLTIGRLEPEDFAVYYCQQYGSSPPWTFGQGTKVA
  			IKR
  60G5.2	VL46	297	SYELTQPPSVSVSPGQTASITCSGNKLGDKYVCWY
  			QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTAT
  			LTISGTQALDEADYYCQAWDSSTWVFGGGTKLTV
  			LG
  61G5	VL59	298	EIMLTQSPGTLSLSPGERATLSCRASQRVPSSYLVW
  			YQQKPGQAPRLLIYGASNRATGIPDRFSGSGSGTD
  			FTLTIGRLEPEDFAVYYCQQYGSSPPWTFGQGTKV
  			AIKR
  52C5	V L73	299	DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWF
  			QQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISSLQPEDFAIYYCQQSSSIPWTFGQGTKVEIKR
  61H5	VL88	300	EIVLTQSPGTLSLSPGERATLSCRASQSVSRDYLAW
  52B9			YRQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCQQYGRSLFTFGPGTTVDIKR
  59D10v1	V L56	301	SYELTQPPSVSVSPGQTARITCSGDAVPKKYANWY
  			QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMAT
  			LTISGAQVEDEADYYCYSTDSSGNHVVFGGGTKL
  			TVLG
  59D10v2	VL57	302	SYELTQPPSVSVSPGQTASITCSGDKLGDKYVCWY
  			QQMPGQSPVLVIHQNNKRPSGIPERFSGSNSGNTA
  			TLTISGTQAMDEADYYCQAWDSSTAVFGGGTKLT
  			VLG
  56G3.2	V L85	303	ETVMTQSPATLSVSPGERATLSCRARQSVGSNLIW
  			YQQKPGQAPRLLIFGASSRDTGIPARFSGSGSGTEF
  			TLTISSLQSEDFAVYYCQQYNNWPLTFGGGTKVEI
  			KR
  48G4	VL89	304	EIVLTQSPGTLSLSPGERATLSCRASQSVASSYLVW
  53C3.1			YQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDF
  			TLTIRRLEPEDFAVYYCQQYGTSPFTFGPGTKVDL
  			KR
  50G1	V L90	305	DIVMTQTPLSLPVSPGEPASISCRSSQSLLDSDDGD
  			TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSVS
  			GSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGG
  			GTKVEIKR
  58C2	VL91	306	EIVMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGD
  			TYLDWYLQKPGQSPQLLIYTLSYRASGVPDRFSGS
  			GSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQ
  			GTRLEIKR
  60G5.1	V L74	1854	DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWF
  			QQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISSLQPEDFATYYCQQSSSIPWTFGQGTKVEIKR
  50D4	VL92	307	DIQMTQSPSSLSASVGDRVTITCRASQDISNYLAW
  			YQQKPGKVPTLLIYAASTLLSGVPSRFSGSGSGTDF
  			TLTISSLQPEDVAAYYCQKYYSAPFTFGPGTKVDI
  			NR
  50G5 v1	VL93	308	DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW
  			YQQKPGKAPNRLIYAASSLQSGVPSRFSGSGSGTE
  			FTLTISSLQPEDFATYYCLQHNSYPRTFGQGTKVEI
  			KR
  50G5 v2	VL94	309	DVVMTQCPLSLPVTLGQPASISCRSSQRLVYSDGN
  			TYLNWVQQRPGQSPRRLIYKVSNWDSGVPDRFSG
  			SGSGTDFTLKISRVEAEDVGVNYCMEGTHWPRDF
  			GQGTRLEIKR
  51C1	VL95	310	DIQMTQSPSSLSASIGDRVTITCRASQSISNYLNWF
  			QQIPGKAPRLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISSLQPEDFATYYCQQSSSIPWTFGQGTTVEIKR
  53C3.2	VL96	311	DIVMTQSPATLSVSPGERATLSCRASQSISSNLAWY
  			QQTPGQAPRLLIYGTSIRASTIPARFSGSGSGTEFTL
  			TISSLQSEDFAIYYCHQYTNWPRTFGQGTKVEIKR
  54H10.3	VL97	312	DIQMTQSPSSLSASVGDRVTITCRASQTISIYLNWY
  			QQKPGKAPKFLIYSASSLQSGVPSRFSGSGSGTDFT
  			LTISSLQPEDFSTYFCQQSYSSPLTFGGGTKVEIKR
  55A7	VL98	313	DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY
  			QQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISSLQPEDFATYYCQQTYSAPFTFGPGTKVDIKR
  55E6	VL99	314	EIVLTQSPGTLSLSPGERATLSCRASQSVSRSHLAW
  			YQQNSGQAPRLLIYGASSRATGIPDRFSGSGSGTDF
  			TLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEI
  			KR
  61E1	V L100	315	DIQMTQSPSSLSASIRDRVTITCRASQSIGTFLNWY
  			QQKPGTAPKLLIYAASSLQSGVPSRFSGSGSGTDFT
  			LTISSLHPEDFASYYCQQSFSTPLTFGGGTKVEITR

• TABLE 2B
  Exemplary Antibody Variable Heavy (VH) Chains

  Contained		SEQ ID
  in Clone	Designation	NO.	Amino Acid Sequence
  63E6	V H 6	316	QVQLMQSGAEVKKPGASVKVSCKASGYTFTGY
  66F7			YMHWVRQAPGQGLEWMGWMNPNSGATKYA
  			QKFQGRVTMTRDTSISTAYMELSRLRSDDTAVY
  			YCARELGDYPFFDYWGQGTLGIVSS
  66D4	V H17	317	QVQLVQSGAEVKKPGASVKVSCRASGYTFTGY
  			YIHWMRQAPGHGLEWMGWINPPSGATNYAQK
  			FRGRVAVTRDTSISTVYMELSRLRSDDTAVYYC
  			ARETGTWNFFDYWGQGTLVTVSS
  66B4	V H10	318	QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY
  			YLHWVRQAPGQGLEWMGWINPNSGGTDYAQK
  			FQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC
  			VGDAATGRYYFDNWGQGTLVTVSS
  65B1	VH18	319	QVQLVQSGAEVKRPGASVKVSCKASGYTFTGY
  			FMHWVRQAPGQGLEWMGWINPNSGATNYAQ
  			KFHGRVTMTRDTSITTVYMELSRLRSDDTAVY
  			YCTRELGIFNWFDPWGQGTLVTVSS
  65B4	V H20	320	EVQLVESGGGLVQPGGSLRLSCAASGFAFSSYD
  			MHWVRQATGKGLEWVSTIDTAGDAYYPGSVK
  			GRFTISRENAKTSLYLQMNSLRAGDTAVYYCTR
  			DRSSGRFGDFYGMDVWGQGTAVTVSS
  67A4	VH19	321	EVQLEESGGGLVQPGGSLRLSCAASGFTFRTYD
  			MHWVRQVTGKGLEWVSAIGIAGDTYYSDSVK
  			GRFTISRENAKNSLYLQMNSLRVGDTAVYYCA
  			RDRSSGRFGDYYGMDVWGQGTTVTVSS
  63A10v1	VH21	322	EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAW
  63A10v2			MSWVRQAPGKGLEWVGRIKSKTDGGTTDYAA
  63A10v3			PVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVY
  			YCTTDSSGSYYVEDYFDYWGQGTLVTVSS
  65H11v1	VH22	323	EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAW
  65H11v2			MSWVRQAPGKGLEWVGRIIGKTDGGTTDYAAP
  			VKGRFTISRDDSKNTLYLQMNSLKTEDTAVYY
  			CTSDSSGSYYVEDYFDYWGQGTLVAVSS
  67G10v1	V H9	324	EVQLVESGGGLVKPGGSLRLACAASGITFNNA
  67G10v2			WMSWVRQAPGKGLEWVGRIKSKTDGGTTDYA
  			APVKGRFTISRDDSKSILYLQMNSLKSEDTAVY
  			YCTTDSSGSYYVEDYFDYWGQGTLVTVSS
  64C8	V H23	325	QVQLVESGGGVVQPGRSLRLSCVASGFTFSSYG
  			MHWVRQDPGKGLEWVAVISYDGSNKHYADSV
  			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			ARELLWFGEYGVDHGMDVWGQGTTVTVSS
  63G8v1	V H1	326	QAQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  63G8v2			IHWVRQAPGKGLEWVAVISYDGSNKYYADSVK
  63G8v3			GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAT
  68D3v1			TVTKEDYYYYGMDVWGQGTTVTVSS
  64A8
  67B4
  68D3v2	VH95	1855	QAQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAFISYAGSNKYY
  			ADSVKGRFTISRDNSKNTLYLQMSSLRAEDTAV
  			YYCATTVTEEDYYYYGMDVWGQGTTVT
  			VSS
  66G2	V H11	327	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAGISYDGSNKNYADSV
  			KGRITISRDNPKNTLYLQMNSLRAEDTAVYYCA
  			TTVTKEDYYYYGMDVWGQGTTVTVSS
  65D1	V H26	328	QVQLVESGGGVVQPGRSLRLSCAASGFTFSYYY
  			IHWVRQAPGKGLEWVALIWYDGSNKDYADSV
  			KGRFTISRDNSKNTLYLHVNSLRAEDTAVYYCA
  			REGTTRRGFDYWGQGTLVTVSS
  64H5	V H7	329	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWDDGSNKYYADS
  			VKGRFTISRDNSKNTLSLQMNSLRAEDTAVYYC
  			AREYVAEAGFDYWGQGTLVTVSS
  65D4	V H25	330	QEQLVESGGGVVQPGRSLRLSCAVSGFTFSFYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CTRALNWNFFDYWGQGTLVTVSS
  65E3	V H24	331	QVQLVESGGGVVQPGRSLRLSCAASGFTLSNYN
  			MHWVRQAPGKGLEWVAVLWYDGNTKYYADS
  			VKGRVTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARDVYGDYFAYWGQGTLVTVSS
  65G4	V H8	332	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWDDGSNKYY
  			ADSVKGRFTISRDNSKNTLSLQMNSLRAEDTAV
  			YYCAREYVAEAGFDYWGQGTLVTVSS
  68G5	V H12	333	QVQLVESGGGVVQPGRSLRLSCTASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYHADS
  			VKGRFTISRDDSKNALYLQMNSLRAEDTAVYY
  			CVRDPGYSYGHFDYWGQGTLVTVSS
  67G8	V H27	334	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKDYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARSAVALYNWFDPWGQGTLVTVSS
  65B7v1	VH28	335	QVQLQESGPGLVNPSQTLSLTCTVSGGSISSDAY
  65B7v2			YWSWIRQHPGKGLEWIGYIFYSGSTYYNPSLKS
  			RVTISVDTSKNRFSLKLSSVTAADTAVYYCARE
  			SRILYFNGYFQHWGQGTLVTVSS
  63B6	V H4	336	QVQLQESGPGLVKPSQTLSLTCAVSGGSISSGDY
  64D4			YWSWIRQHPGKGLEWIGYIYYSGTTYYNPSLKS
  			RVTISVDTSKNQFSLKLTSVTAADTAVYYCARM
  			TTPYWYFGLWGRGTLVTVSS
  63F5	V H13	337	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY
  			YWTWIRQHPGKDLEWITYIYYSGSAYYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCARM
  			TTPYWYFDLWGRGTLVTVSS
  63H11	V H3	338	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY
  			YWTWIRQHPGKGLEWIAYIYYSGSTYYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCARM
  			TTPYWYFDLWGRGTLVTVSS
  65E8	V H2	339	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY
  64E6			YWTWIRQHPGKGLEWIAYIYYTGSTYYNPSLKS
  65F11			RVTISVDTSKNQFSLKLSSVTAADTAVYYCARM
  67G7			TTPYWYFDLWGRGTLVTVSS
  65C1	V H15	340	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY
  			YWTWIRQHPGKGLEWIAYIFYSGSTYYNPSLKS
  			RVTISLDTSKNQFSLKLNSVTAADTAVYYCARM
  			TSPYWYFDLWGRGTLVTVSS
  66F6	V H14	341	QVQLQESGPGLVKPSQTLSLTCPVSGGSISSGDY
  			YWTWIRHHPGKGLEWIAYIYYSGSTYYNPSLKS
  			RVTISVDTSKNQFSLKLNSVTAADTAVYYCAR
  			MTTPYWYFDLWGRGTLVTVSS
  64A6	VH29	342	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGY
  			YWSWIRQRPGKGLEWVGYIYYSGGTHYNPSLK
  			SRVTISIDTSENQFSLKLSSVTAADTAVYYCARV
  			LHYSDSRGYSYYSDFWGQGTLVTVSS
  65F9	V H30	343	QVQLQESGPGLVKPSQTLSLTCTLSGGSFSSGDY
  			YWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKS
  			RVTISIDTSKNQFSLKLTSVTAADTAVYYCARV
  			LHYYDSSGYSYYFDYWGQGTLVTVSS
  64A7	V H16	344	QLQLQESGPGLVKPSETLSLTCTVSGGSISSDTS
  			YWGWIRQPPGKGLEWIGNIYYSGTTYFNPSLKS
  			RVSVSVDTSKNQFSLKLSSVTAADTAVFYCARL
  			RGVYWYFDLWGRGTLVTVSS
  65C3	V H5	345	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW
  68D5			SWIRQPPGKGLEWIGYIYYTGSTNYNPSLKSRV
  			TISVDTSKNQFSLKLSSVTAADTAVYYCAREYY
  			YGSGSYYPWGQGTLVTVSS
  67F5	V H31	346	QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYW
  			SWIRQPPGKGLEWIGYIYYSGNTNYNPSLKSRV
  			TISVDTSKNQFSLKLSSVTAADTAVYYCAREYY
  			YGSGSYYPWGQGTLVTVSS
  64B10v1	VH32	347	QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDY
  			YWSWIRQPPGKGLEWIGFIYYSGGTNYNPSLKS
  			RVTISIDTSKNQFSLKLNSVTAADTAVYYCARY
  			SSTWDYYYGVDVWGQGTTVTVSS
  64B10v2	VH96	1856	QVQLLESGPGLVKPSETLSLTCTVSGGSVSSGD
  			YYWSWIRQPPGKGLEWIGFIYYSGGTNYNPPLK
  			SRVTISIDTSKNQFSLKLSSVTAADTAVYYCARY
  			SSTWDYYYGVDVWGQGTTVTVSS
  68C8	VH33	348	QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGD
  			NYWSWIRQPPGKGLEWIGFMFYSGSTNYNPSL
  			KSRVTISLHTSKNQFSLRLSSVTAADTAVYYCG
  			RYRSDWDYYYGMDVWGQGTTVTVSS
  67A5	VH34	349	EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYW
  			IGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQG
  			QVTISADKSINTAYLQWSSLKASDTAIYFCARR
  			ASRGYRFGLAFAIWGQGTMVTVSS
  67C10	VH35	350	EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYW
  			IGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQG
  			QVTISADKSINTAYLQWSSLKASDTAIYYCARR
  			ASRGYRYGLAFAIWGQGTMVTVSS
  64H6	VH36	351	EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYW
  			IGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQG
  			QVTISADKSISTAYLQWNSLKTSDTAMYFCATV
  			AVSAFNWFDPWGQGTLVTVSS
  63F9	VH37	352	QVQLKESGPGLVKPSQTLSLTCTVSGGSISSGGY
  			YWNWIRQHPGKGLEWIGYIYDSGSTYYNPSLKS
  			RVTMSVDTSKNQFSLKLSSVTAADTAVYYCAR
  			DVLMVYTKGGYYYYGVDVWGQGTTVTVSS
  67F6v1	V H38	353	EVQLVQSGAEVKKPGESLKISCKGSGYSFTGYW
  67F6v2			IGWVRQLPGKGLEWMGIIYPGDSDTRYSPSFQG
  			QVTISVDKSINTAYLQWSSLKASDTAMYYCAR
  			RASRGYSYGHAFDFWGQGTMVTVSS
  48C9	V H73	354	QVQLQQWGAGLLKPSETLSLTCSVYGGSFSGY
  49A12			YWTWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  51E2			RVTISIDTSKNQFSLKLSSVTAADTAVYYCARES
  			GNFPFDYWGQGTLVTVSS
  48F3	V H72	355	QVQLQQWGAGPLKPSETLSLTCAVYGGSISGYY
  			WSWIRQPPGKGLEWIGEITHTGSSNYNPSLKSR
  			VTISVDTSKNQFSLKLSSVTAADTAVYYCARGG
  			ILWFGEQAFDIWGQGTMVTVSS
  48F8	VH48	356	EVQLVESGGGLVKPGGSLRLSCTASGFTFRSYS
  53B9			MNWVRQAPGKGLEWVSSISSSSSYEYYVDSVK
  56B4			GRFTISRDIAKSSLWLQMNSLRAEDTAVYYCAR
  57E7			SLSIAVAASDYWGKGTLVTVSS
  57F11
  48H11	VH39	357	QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY
  			YKHWVRQAPGQGLEWMGWINPNSGATKYAQ
  			KFQGRVTMTRDTSISTVYMELSRLRSVDTALYY
  			CAREVPDGIVVAGSNAFDFWGQGTMVTVSS
  49A10	VH62	358	QVHLVESGGGVVQPGRSLRLSCAASGFTFSNYG
  48D4			MHWVRQAPGKGLEWVAIIWYDGSNKNYADSV
  			KGRFTISRDNSKNTLYLEMNSLRAEDTAVYYCA
  			RDQDYDFWSGYPYFYYYGMDVWGQGTTVTVSS
  49C8	VH44	359	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY
  52H1			DIDWVRQATGQGLEWMGWMNPNGGNTGYAQ
  			KFQGRVTMTRNTSINTAYMELSSLRSEDTAIYY
  			CARGKEFSRAEFDYWGQGTLVTVSS
  49G2	VH63	360	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYG
  50C12			MRWVRQAPGKGLEWVALIWYDGSNKFYADSV
  55G11			KGRFTISRDNSKNTLNLQMNSLRAEDTAVYYC
  			ARDRYYDFWSGYPYFFYYGLDVWGQGTTVTV
  			SS
  49G3	VH46	361	QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRM
  			GVSWIRQPPGKALEWLTHIFSNDEKSYSTSLKSR
  			LTISKDTSKSQVVLSMTNMDPVDTATYYCVRV
  			DTLNYHYYGMDVWGQGTTVTVSS
  49H12	VH42	362	QVQLVQSGAEVKKPGASVKVSCMASGYIFTSY
  			DINWVRQATGQGPEWMGWMNPYSGSTGYAQ
  			NFQGRVTMTRNTSINTAYMELSSLRSEDTAVYY
  			CAKYNWNYGAFDFWGQGTMVTVSS
  51A8	VH58	363	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVISYDGSNKYYADSV
  			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			ARADGDYPYYYYYYGMDVWGQGTTVTVSS
  51C10.1	VH54	364	EVQLLESGGGLVQPGGSLRLSCAASGFTFRNYA
  59D10v1			MSWVRQAPGKGLEWVSGISGSSAGTYYADSVK
  59D10v2			GRFTISRDNSKNTLFLQMDSLRAEDTAVYYCAQ
  			DWSIAVAGTFDYWGQGTLVTVSS
  51C10.2	VH67	365	QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGY
  			YWSWIRQHPGKGLEWIGYIYYNGSPYDNPSLK
  			RRVTISIDASKNQFSLKLSSMTAADTAVYYCAR
  			GALYGMDVWGQGTTVTVSS
  51E5	V H74	366	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGELDHSGSINYNPSLKS
  			RVTISVDTSKNQFSLKLTSVTAADTAVYYCARV
  			LGSTLDYWGQGTLVTVSS
  51G2	V H50	367	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  			MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK
  			GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCA
  			RDTYISGWNYGMDVWGQGTTVTVSS
  52A8	V H40	368	QVQLVQSGAEVKKPGASVKVSCKASGYTFTGY
  			YLHWVRQAPGQGLEWMGWINPNSAATNYAPK
  			FQGRVTVTRDTSISTAYMELSRLRSDDTAVYYC
  			AREGGTYNWFDPWGQGTLVTVSS
  52B8	VH77	369	QVQLQESGPGLMKPSETLSLTCTVSGGSISYYY
  			WSWIRQSPGKGLEWIGYIYYSGSTNYNPSLKSR
  			VTMSVDTSKNQFSLKLSSVTAADTAVYYCASG
  			TRAFDIWGQGTMVTVSS
  52C1	V H64	370	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSNNYYADS
  			VKGRFTISRDNSKSTLFLQMNSLRAEDTAIYYC
  			ARDRAGASPGMDVWGQGTTVTVSS
  52F8	VH41	371	QVQLVQSGAEVKKPGASVKVSCKASGFTFIGY
  			YTHWVRQAPGQGLEWMGWINPSSGDTKYAQK
  			FQGRVTLARDTSISTAYMELSRLRSDDTAVYYC
  			ANSGWYPSYYYGMDVWGQGTTVTVSS
  52H2	VH79	372	QVQLQESGPGLVKPSETLSLTCTVSGGSISTYY
  			WSWIRQPPGTGLEWIGYIFYNGNANYSPSLKSR
  			VTFSVDTSKNQFSLKLSSVTAADTAVYFCARET
  			DYGDYARPFEYWGQGTLVTVSS
  53F6	V H60	373	QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARGHYDSSGPRDYWGQGTLVTVSS
  53H5.2	VH59	374	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGQGLEWVALISYDGSNKYYADSV
  			KGRFTISRDKSKNTLYLQMNSLRAEDTAVYYC
  			AREANWGYNYYGMDVWGQGTTVTVSS
  53H5.3	VH75	375	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDY
  			YWNWIRQPPGKGPEWIGEINHSGTTNYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCVGI
  			LRYFDWLEYYFDYWGQGTLVTVSS
  54A1	V H43	376	QVQLVQSGAEVKKPGASVKVSCKASGYTFTSY
  55G9			DINWVRQATGQGLEWMGWMNPHSGNTGYAQ
  			KFQGRVTMTRNTSINTAYMELSSLRSEDTAVYY
  			CAKYNWNYGAFDFWGQGTMVTVSS
  54H10.1	V H52	377	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  55D1			MSWVRQAPGKGLEWVSAISGSGRTTYSADSVK
  48H3			GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
  53C11			KEQQWLVYFDYWGQGTLVTVSS
  55D3	VH68	378	QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGVY
  			YWNWIRQHPGKGLEWIGYLYYSGSTYYNPSLK
  			SRLTISADMSKNQFSLKLSSVTVADTAVYYCAR
  			DGITMVRGVTHYYGMDVWGQGTTVTVSS
  55E4	V H70	379	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  49B11			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  50H10			RVTISLDTSNDQFSLRLTSVTAADTAVYYCARV
  53C1			TGTDAFDFWGQGTMVTVSS
  52C5
  60G5.1
  55E9	V H65	380	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSFG
  			MHWVRQAPGKGLEWVALIWYDGDNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARNSGWDYFYYYGMDVWGQGTTVTVSS
  55G5	VH78	381	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW
  			SWIRQPAGKGLEWIGRIYISGSTNYNPSLENRVT
  			MSGDTSKNQFSLKLNSVTAADTAVYYCAGSGS
  			YSFDYWGQGTLVTVSS
  50G1	VH84	382	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			LHWVRQAPGKGLEWVAVIWNDGSNKLYADSV
  			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			ARDQYYDFWSGYPYYHYYGMDVWGQGTTVT
  			VSS
  56A7	VH51	383	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  56E4			MNWVRQAPGKGLEWVSSISSSSTYIYYADSVK
  			GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCA
  			RDIYSSGWSYGMDVWGQGTTVTVSS
  56C11	VH61	384	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSYQFYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARDHVWRTYRYIFDYWGQGTLVTVSS
  56E7	V H81	385	EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWI
  			GWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQG
  			QVTISADTSISTAYLQWSRLKASDTAVYYCARA
  			QLGIFDYWGQGTLVTVSS
  56G1	V H71	386	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  			RVTISLDTSNKQFSLRLTSVTAADTAVYYCARV
  			TGTDAFDFWGQGTMVTVSS
  56G3.3	VH76	387	QLQLQESGPGLVKPSETLSLTCTVSGDSISSSSY
  55B10			YWGWIRQPPGKGLEWIGMIYYSGTTYYNPSLK
  			SRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR
  			VAAVYWYFDLWGRGTLVTVSS
  57B12	VH69	388	QVQLQESGPGLVKPSQTLSLTCTVSGGSITSGVY
  			YWSWIRQLPGKGLEWIGYIYYSGSTYYNPSLKS
  			RLTISADTSKNQFSLKLSSVTVADTAVYYCARD
  			GITMVRGVTHYYGMDVWGQGTTVTVSS
  57D9	VH82	389	QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSA
  			TWNWIRQSPSRGLEWLGRTYYRSKWYNDYAV
  			SVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC
  			VGIVVVPAVLFDYWGQGTLVTVSS
  58C2	V H85	390	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYG
  			MHWVRQAPGKGLEWVAVIWNDGNNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
  			CARDQNYDFWNGYPYYFYYGMDVWGQGTTV
  			TVSS
  59A10	VH47	391	QVQVVESGGGLVKPGGSLRLSCAASGFTFSDSY
  49H4			MSWIRQAPGKGLEWISSISSSGSIVYFADSVKGR
  			FTISRDIAKNSLYLHMNSLRAEDTAVYYCARET
  			FSSGWFDAFDIWGQGTMVTVSS
  59C9	VH49	392	EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYS
  58A5			MSWVRQAPGKGLEWVSSISSSSTYIYYADSLKG
  57A4			RFTISRDNAKNSLFLQVNSLRAEDSAVYYCARD
  57F9			RWSSGWNEGFDYWGQGTLVTVSS
  59G10.2	VH57	393	QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYG
  			MHWVRQAPGKGLEWVAITSYGGSNKNYADSV
  			KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
  			AREAGYSFDYWGQGTLVTVSS
  59G10.3	V H53	394	EVQLLGSGGGLVQPGGSLRLSCAASGFTFNHYA
  			MSWVRQAPGKGLEWVSAISGSGAGTFYADSM
  			KGRFTISRDNSENTLHLQMNSLRAEDTAIYYCA
  			KDLRIAVAGSFDYWGQGTLVTVSS
  60D7	V H66	395	QVQLVESGGGVVQPGRSLRLSCAASGFNFSSYG
  			MHWVRQAPGKGLEWVAVIWYDGSNKYYADS
  			VKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYC
  			ARDQYFDFWSGYPFFYYYGMDVWGQGTTVTV
  			SS
  60F9	VH55	396	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  48B4			MSWVRQAPGKGLEWVSVISDSGGSTYYADSVK
  52D6			GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
  			KDHSSGWYYYGMDVWGQGTTVTVSS
  60G5.2	VH45	397	QVQLVQSGAEVKTPGASVRVSCKASGYTFTNY
  			GISWVRQAPGQGLEWMGWISAYNGYSNYAQK
  			FQDRVTMTTDTSTSTAYMELRSLRSDDTAVYY
  			CAREEKQLVKDYYYYGMDVWGQGSTVTVSS
  61G5	V H56	398	EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYA
  			MSWVRQSPGKGLEWVSVISGSGGDTYYADSVK
  			GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
  			KDHTSGWYYYGMDVWGQGTTVTVSS
  56G3.2	V H80	399	QVQLQESGPGLVKPSETLSLTCTVSDGSISSYYW
  			NWIRQPAGKGLEWIGRIYTSGSTNYNPSLKSRV
  			TMSVDTSKNQFSLNLTSVTAADTAVYYCARGP
  			LWFDYWGQGTLVTVSS
  48G4	VH83	400	QVQLVQSGAEVKKPGASVKVSCKVSGYTLTEL
  53C3.1			SIHWVRQAPGKGLEWMGGFDPEDGETIYAQKF
  			QGRVTMTEDTSTDTAYMELSSLRSEDTAVYYC
  			ATHSGSGRFYYYYYGMDVWGQGTTVTVSS
  61H5	VH86	401	QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSY
  52B9			YWGWIRQPPGKGLEWIGSIYYSGTTYYNPSLKS
  			RVTISVDTSKNQFSLKLSSVTAADTAVYYCARV
  			AAVYWYFDLWGRGTLVTVSS
  50D4	VH87	402	QVQLVQSGAEVKKTGASVKVSCKASGYTFTSH
  			DINWVRQATGHGLEWMGWMNPYSGSTGLAQR
  			FQDRVTMTRNTSISTAYMELSSLRSEDTAVYYC
  			ARDLSSGYYYYGLDVWGQGTTVTVSS
  50G5v1	VH88	403	QVQLVQSGAEVKKPGASVKVSCKASGYPFIGY
  50G5v2			YMHWVRQAPGQGLEWMGWINPDSGGTNYAQ
  			KFQGRVTMTRDTSITTAYMELSRLRSDDTAVFY
  			CARGGYSYGYEDYYGMDVWGQGTTVTVSS
  51C1	VH89	404	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGY
  			YWSWIRQPPGKGLEWIGEINHSENTNYNPSLKS
  			RVTISLDTSHDQFSLRLTSVTAADTAVYYCARV
  			TGTDAFDFWGQGTMVTVSS
  53C3.2	V H90	405	QVQLQESGPGLVKPSQTLSLTCTVSNGSINSGN
  			YYWSWIRQHPGKGLEWIGYIYHSGSAYYNPSL
  			KSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA
  			RTTGASDIWGQGIMVTVSS
  54H10.3	VH91	406	DIQMTQSPSSLSASVGDRVTITCRASQTISIYLN
  			WYQQKPGKAPKFLIYSASSLQSGVPSRFSGSGS
  			GTDFTLTISSLQPEDFSTYFCQQSYSSPLTFGGGT
  			KVEIKR
  55A7	VH92	407	QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYW
  			SWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVT
  			ISVDTSKNQFSLRLSSVTAADTAVYYCARGITGT
  			IDFWGQGTLVTVSS
  55E6	VH93	408	EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYS
  			MNWVRQAPGKGLEWISYISSGSSTIYHADSVKG
  			RFTISRDNAKNSLYLQMNSLRDEDTAVYYCAR
  			EGYYDSSGYYYNGMDVWGQGTTVTVSS
  61E1	VH94	409	QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSA
  			AWNWIRQSPSRGLEWLGRTYYRSKWYNDYAV
  			SVKSRITITPDTSKNQFSLQLKSVTPEDTAIYYCA
  			REGSWSSFFDYWGQGTLVTVSS

• TABLE 2C
  Coding Sequence for Antibody Variable Light (VL) Chains

  Contained		SEQ ID
  in Clone	Designation	NO.	Coding Sequence

  63E6	VL6	410	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGACAAGTCAGAGTATTAGCAGCTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			ACCTCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGATTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCGGTCTG
  			CAACCTGAAGATTTTTCAACTTACTACTGTCAAC
  			AGAGTTACAGTACCTCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCAAACGA
  66D4	VL18	411	GACATCCAGATGACCCAGTCGCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGGATCACCATCACTT
  			GCCGGGCAAGTCAGATCATTAGCAGGTATTTAA
  			ATTGGTATCAGCAGAACCCAGGGAAAGCCCCTA
  			AGCTCCTGATCTCTGCTGCATCCAGTTTGCAAAG
  			TGGAGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGCCAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTACAACTTACTACTGTCAAC
  			AGAGTTACAGTTCCCCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGGTCAAACGA
  66B4	VL11	412	GACATCCAGATGACCCAGTCTCCATCTTCCGTGT
  			CTTCATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCAGGGTATTAGCAGGTGGTTAG
  			CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTATGCTGCATCCAGTTTGAAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTACTATTGTCAA
  			CAGGCTAACAGTTTCCCTCCGACGTTCGGCCAA
  			GGGACCAAGGTGGAAATCAAACGA
  65B1	VL19	413	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAACATTAACAACTATTTAA
  			ATTGGTATCGGCAGAAACCAGGGAAAGCCCCTG
  			AACTCCTGATCTATACTACATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			GAAACTGAAGATTTTGAAACTTACTACTGTCAA
  			CAGAGTTACAGTACCCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  65B4	VL21	414	TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAG
  			TGGCCCCAGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTAAAAGTGTGCAGT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC
  			TGGTCGTCTACGATGATAGCGACCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACGGCCTCCCTGACCATCAGCAGGGTCGA
  			AGCCGGGGATGAGGCCGACTATTACTGTCAGGT
  			GTGGGATAGTAGTAGTGATCATGTGGTATTCGG
  			CGGAGGGACCAAGCTGACCGTCCTAGGT
  67A4	V L20	415	TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAG
  			TGGCCCCAGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTAAAAGTGTGCACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC
  			TGGTCGTCTATGATGATAGCGACCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACGGCCACCCTGACCATCAGCAGGGTCGA
  			AGCCGGGGATGAGGCCGACTATTACTGTCAGGT
  			GTGGGATAGTAGTAGTGATCATGTGGTATTCGG
  			CGGAGGGACCAAGCTGACCGTCCTAGGT
  63A10v1	VL22	416	TCCTATGAGCTGACTCAGCCACACTCAGTGTCA
  			GTGGCCACAGCACAGATGGCCAGGATC
  			ACCTGTGGGGGAAACAACATTGGAAGTAAAGCT
  			GTGCACTGGTACCAGCAAAAGCCAGGC
  			CAGGACCCTGTGCTGGTCATCTATTGCGATAGC
  			AACCGGCCCTCAGGGATCCCTGAGCGA
  			TTCTCTGGCTCCAACCCAGGGAACACCGCCACC
  			CTAACCATCAGCAGGATCGAGGCTGGG
  			GATGAGGCTGACTATTACTGTCAGGTGTGGGAC
  			AGTAGTAGTGATGGGGTATTCGGCGGA
  			GGGACCAAGCTGACCGTCCTAGGT
  63A10v2	VL101	1857	TCCTATGAGCTGACTCAGCCACACTCAGTGTCA
  			GTGGCCACAGCACAGATGGCCAGGATC
  			ACCTGTGGGGGAAACAACATTGGAAGTAAAGCT
  			GTGCACTGGTACCAGCAAAAGCCAGGC
  			CAGGACCCTGTGCTGGTCATCTATTGCGATAGC
  			AACCGGCCCTCAGGGATCCCTGAGCGA
  			TTCTCTGGCTCCAACCCAGGGAACACCGCCACC
  			CTAACCATCAGCAGGATCGAGGCTGGG
  			GATGAGGCTGACTATTACTGTCAGGCGTGGGAC
  			AGCACCACTGTGGTATTCGGCGGAGGG
  			ACCAAGTTGACCGTCCTAGGT
  63A10v3	VL102	1858	ACCTGCTCTGGAGATAAATTGGGGAATAGATAT
  			ACTTGCTGGTATCAGCAGAAGTCAGGC
  			CAGTCCCCTGTGCTGGTCATCTATCAAGATAGCG
  			AGCGGCCCTCAGGGATCCCTGAGCGA
  			TTCTCTGGCTCCAACTCTGGGAACACAGCCACTC
  			TGACCATCAGCGGGACCCAGGCTATG
  			GATGAGGCTGACTATTACTGTCAGGCGTGGGAC
  			AGCACCACTGTGGTATTCGGCGGAGGG
  			ACCAAGTTGACCGTCCTAGGT
  65H11v1	V L23	417	TCCTATGAGCTGACTCAGCCACACTCAGTGTCA
  			GTGGCCACAGCACAGATGGCCAGGATCACCTGT
  			GGGGGAAACAACATTGGAAGTAAAACTGTGCAC
  			TGGTTCCAGCAAAAGCCAGGCCAGGACCCTGTG
  			CTGGTCATCTATAGCGATAGCAACCGGCCCTCA
  			GGGATCCCTGAGCGATTCTCTGGCTCCAACCCA
  			GGGAACACCGCCACCCTAACCATCAGCAGGATC
  			GAGGCTGGGGATGAGGCTGACTATTACTGTCAG
  			GTGTGGGACAGTAGTTGTGATGGGGTATTCGGC
  			GGAGGGACCAAGCTGACCGTCCTAGGT
  65H11v2	VL103	1859	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAACATC
  			ACCTGCTCTGGAGATAAATTGGGGGATAGATAT
  			GTTTGTTGGTATCAGCAGAAGCCAGGC
  			CAGTCCCCTGTGCTGGTCATCTATCAAGATAGCA
  			AGCGGCCCTCAGGGATCCCTGAACAA
  			TTCTCTGGCTCCAACTCTGGGAACACAGCCACTC
  			TGACCATCAGCGGGACCCAGGCTATA
  			GATGAGGCTGACTATTACTGTCAGGCGTGGGAC
  			AGCATCACTGTGGTATTCGGCGGAGGG
  			ACCAAGCTGACCGTCCTAGGT
  67G10v1	V L9	418	TCCTATGAGCTGACTCAGCCACACTCAGTGTCA
  			GTGGCCACAGCACAGATGGCCAGGATCACCTGT
  			GGGGGAAACAACATTGGAAGTAAAGCTGTGCAC
  			TGGTACCAGCAAAAGCCAGGCCAGGACCCTGTG
  			CTGGTCATCTATAGCGATAGCAACCGGCCCTCA
  			GGGATCCCTGAGCGATTCTCTGGCTCCAACCCA
  			GGGAACACCGCCACCCTAACCATCAGCAGGATC
  			GAGGCTGGGGATGAGGCTGACTATTACTGTCAG
  			GTGTGGGACAGTAGTAGTGATGGGGTATTCGGC
  			GGAGGGACCAAGCTGACCGTCCTAGGT
  67G10v2	V L10	419	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAGATAAATTGGGGGATAAATATGCTTGCT
  			GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGC
  			TGGTCATCTATCAAGATAACGAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTATGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCACCACTGTGGTATTCGGCGGAGG
  			GACCAAGCTGACCGTCCTAGGT
  64C8	V L24	420	GATGTTGTGATGACTCAGTCTCCGCTCTCCCTGC
  			CCGTCACCCTTGGACAGCCGGCCTCCATCTCCCG
  			CAGGTCTAGTCCAAGCCTCGTATACAGTGATGG
  			AAACACCTACTTGAATTGCTTTCAGCAGAGGCC
  			AGGCCACTCTCCAAGGCGCCTAATTTATAAGGG
  			TTCTAACTGGGACTCAGGGGTCCCAGACAGATT
  			CAGCGGCAGTGGGTCAGGCACTGATTTCACTCT
  			GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGG
  			TATTTATTACTGCATACAAGATACACACTGGCCC
  			ACGTGCAGTTTTGGCCAGGGGACCAAGCTGGAG
  			ATCAAACGA
  64A8	V L1	421	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  67B4			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGACATTAGAAATGATTTAG
  			GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCGCCTGATCTATGCTGCATCCAATTTGCAAA
  			GGGGGGTCCCATCAAGGTTCAGCGGCAGTGGAT
  			CTGGGACAGAATTCACTCTCACAATCAGCACCC
  			TGCAGCCTGAAGATTTTGCAACTTATTCCTGTCT
  			CCAGCATAATAGTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  63G8v1	VL104	1860	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACC
  			ATCACTTGCCGGGCAAGTCAGGACATTAGAAAT
  			GATTTAGGCTGGTATCAACAGAAACCA
  			GGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA
  			TCCAATTTGCAAAGGGGGGTCCCATCA
  			AGGTTCAGCGGCAGTGGATCTGGGACAGAATTC
  			ACTCTCACAATCAGCACCCTGCAGCCT
  			GACGATTTTGCAACTTATTCCTGTCTCCAGCATA
  			ATAGTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  63G8v2	VL105	1861	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACC
  			ATCACTTGCCGGGCAAGTCAGGGCATTAGAAGT
  			GGTTTAGGCTGGTATCAGCAGAAACCA
  			GGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA
  			TCCAATTTGCAAAGGGGGGTCCCATCA
  			AGGTTCAGCGGCAGTGGATCTGGGACAGAATTC
  			ACTCTCACAGTCAGCAGTCTGCAGCCT
  			GAAGATTTTGCAACTTATTCCTGTCTCCAGCATA
  			ATAGTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  63G8v3	VL106	1862	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACC
  			ATCACTTGCCGGGCAAGTCAGGGCATTAGAAGT
  			GGTTTAGGCTGGTATCAACAGAAACCA
  			GGGAAAGCCCCTAAGCGCCTGATCTATGCTGCA
  			TCCAATTTGCAAAGGGGGGTCCCATCA
  			AGGTTCAGCGGCAGTGGATCTGGGACAGAATTC
  			ACTCTCACAGTCAGCAGTCTGCAGCCT
  			GAAGATTTTGCAACTTATTCCTGTCTCCAACATA
  			ATACTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGGGGAGATCAGACGA
  66G2	V L12	422	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGGCATTAGAAATGATTTAG
  			GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCGCCTGATCTATGCTGCATCCAATTTGCAAA
  			GTGGGGTCCCATCAAGGTTCAGCGGCAGTGGAT
  			CTGGGACAAAATTCACTCTCACAATCAACAGCC
  			TGCAGCCTGAAGATTTTGCAACTTATTACTGTCT
  			ACAACTTAATGGTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  68D3v1	V L2	423	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  68D3v2			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGACATTAGAAATGATTTAG
  			GCTGGTATCAACAGAAACCAGGGAAAGCCCCTA
  			AGCGCCTGATCTATGCTGCATCCAATTTGCAAA
  			GGGGGGTCCCATCAAGGTTCAGCGGCAGTGGAT
  			CTGGGACAGAATTCACTCTCACAATCAGCACCC
  			TGCAGCCTGACGATTTTGCAACTTATTCCTGTCT
  			CCAGCATAATAGTTACCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  65D1	V L27	424	TCCTATGACCTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAGATAAATTGGGGGATAAATATGTTTGCT
  			GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGC
  			TGGTCATCTATCAAGATAGTAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGATCCA
  			GGCTATGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCAGGGTATTCGGCGGAGGGACCA
  			AGCTGACCGTCCTAGGT
  65G4	V L8	425	TCCTATGAGATGACTCAGCCACTCTCAGTGTCAG
  64H5			TGGCCCTGGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTAAAAATGTACACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGT
  			TGGTCATCTATAGGGATAGCAAGCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GGAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATTACTGTCAGG
  			TGTGGGACAGCAGTAGTGTGGTATTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  65D4	V L26	426	TCCTATGAGCTGACTCAGCCACTCTCAGTGTCTG
  			TGGCCCTGGGCCAGACGGCCAGGATTCCCTGTG
  			GGGGAAATGACATTGGAAGTAAAAATGTGCACT
  			GGTACCAGCAGAAACCAGGCCAGGCCCCTGTGC
  			TGGTCATCTATAGGGATCGCAACCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GGAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATTACTGTCAGG
  			TGTGGGACAGCAACCCTGTGGTATTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  65E3	V L25	427	TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG
  			TGGCCCTGGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTAAAAATGTGCACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC
  			TGGTCATCTATAGGGATAGAAACCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GGAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATTACTGTCAGG
  			TGTGGGACAGCAGCACTGTGGTCTTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  68G5	V L13	428	TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG
  			TGGCCCTGGGACAGACGGCCAGGCTTACCTGTG
  			GGGGTAACAACATTGGAAGTATAAATGTGCACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGT
  			TGGTCATCTATAGGGATAGGAACCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GTAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATTACTGTCAGT
  			TGTGGGACAGCAGCACTGTGGTTTTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  67G8	VL28	429	TCCTATGAGCTGACTCAGCCACTCTCAGTGTCAG
  			TGGCCCTGGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTTACAATGTGTTCT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC
  			TGGTCATCTATAGGGATAGCAAGCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GGAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATCACTGTCAGG
  			TGTGGGACAGCAGCACTGTGGTATTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  65B7v1	VL29	430	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACC
  			CTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGC
  			ATCTACTTAGCCTGGTACCAGCAGAAA
  			CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTG
  			CATCCAGCAGGGCCACTGGCATCCCA
  			GACAGGTTCAGTGGCAGTGGGTCTGGGACAGAC
  			TTCACTCTCACCATCAGCAGACTGGAG
  			CCTGAAGATTTTGCAGTGTATTACTGTCAGCAGT
  			ATGGTAGCTCGTGCAGTTTTGGCCAG
  			GGGACCAAGCTGGAGATCAAACGA
  65B7v2	VL107	1863	GATGTTGTGATGACTCAGTCTCCACTCTCCCTGC
  			CCGTCACCCTTGGACAGCCGGCCTCC
  			ATCTCCTACAGGTCTAGTCAAAGCCTCGTATACA
  			GTGATGGAGACACCTACTTGAATTGG
  			TTTCAGCAGAGGCCAGGCCAATCTCCAAGGCGC
  			CTAATTTATAAGGTTTCTAACTGGGAC
  			TCTGGGGTCCCAGACAGATTCAGCGGCAGTGGG
  			TCAGGCACTGATTTCACACTGAAAATC
  			AGCAGGGTGGAGGCTGAGGATGTTGGGGTTTAT
  			TACTGCATGCAAGGTACACACTGGCGG
  			GGTTGGACGTTCGGCCAAGGGACCAAGGTGGAA
  			ATCAAACGA
  63B6	V L4	431	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  64D4			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGTAACAGCTACT
  			TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATTCAGTAGGGC
  			CACTGGCATCCCAGACAGGTTCAGTGGCAGTGG
  			GTCTGGGACAGACTTCACTCTCACCATCAGCAG
  			ACTGGAGCCTGAAGATTTTGCAGTATATTACTGT
  			CAGCAGTTTGGTAGGTCATTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAGACGA
  63F5	V L14	432	GAAGTTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGACTGTTAGGAACAACTACT
  			TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTTTGGTGCGTCCAGCAGGGC
  			CACTGGCATCCCAGACAGGTTCAGTGGCAGTGG
  			GTCTGGGACAGACTTCACTCTCACCATCAGCAG
  			ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT
  			CAGCAGTTTGGTAGTTCACTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCAAACGA
  65E8	V L3	433	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  63H11			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  64E6			GCAGGGCCAGTCAGAGTGTTAGGAACAGCTACT
  65F11			TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC
  67G7			CCAGGCTCCTCATCTATGGTGCATTTAGCAGGGC
  			CTCTGGCATCCCAGACAGGTTCAGTGGCAGTGG
  			GTCTGGGACAGACTTCACTCTCACCATCAGCAG
  			ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT
  			CAGCAGTTTGGAAGCTCACTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  65C1	VL16	434	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGACTATTAGGAACAGCTACT
  			TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATTCAGCAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCGGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTTTGGTAGCTCACTCACTTTCGGCGG
  			AGGGACCAAGGTGGAGATCAAACGA
  66F6	VL15	435	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGGAACAGCTACT
  			TAGCCTGGTACCAGCAGCAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATTCAGCAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTTTGGTAGCTCACTCACTTTCGGCGG
  			AGGGACCAAGGTGGAGATCAAACGA
  64A6	VL30	436	GAAATACTGATGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAACAGCAACTTAG
  			CCTGGTACCAGCAGAAACCTGGCCAGGCTCCCA
  			GGCTCCTCATCTATGGTACATCCACCAGGGCCA
  			CTGGTGTCCCAGCCAGGTTCGGTGGCAGTGGGT
  			CTGGGACAGAATTCACTCTCACCATCAGCAGCC
  			TGCAGTCTGAAGATTTTGCATTTTATTACTGTCA
  			GCAATATAATACCTGGCCGTGGACGTTCGGCCA
  			AGGGACCAAGGTGGAAATCAAACGA
  65F9	VL31	437	GAAATACTGATGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAG
  			CCTGGTACCAGCAGAAACCTGGCCAGTCTCCCA
  			GGCTCCTCATCTATGGTGCATCCACCAGGGCCA
  			CTGGTATCCCAGCCAGGTTCGGTGGCAGTGGGT
  			CTGGGACAGACTTCACTCTCACCATCAGCAGCC
  			TGCAGTCTGAAGATTTTGCATTTTATTACTGTCA
  			GCAGTATAATACCTGGCCGTGGACGTTCGGCCA
  			AGGGACCAAGGTGGAAATCAAACGA
  64A7	V L17	438	GAAATTGTATTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGTCGCAACTACT
  			TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAGCAGGG
  			CCACTGGCGTCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTAGTTCATCTCTGTGCAGTTT
  			TGGCCAGGGGACCAACCTGGACATCAGACGA
  65C3	V L5	439	GAAATGGTGATGACGCAGTCCCCAGCCACCCTG
  68D5			TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGCCAGTTAG
  			CCTGGTACCAGGAGAAACCTGGCCGGGCTCCCA
  			GGCTCCTCATCTATGGTGCCTCCAACAGGGCCAT
  			TGATATCCCAGCCAGGTTAAGTGGCAGTGGGTC
  			TGGGACAGAGTTCACTCTCACCATCAGCAGCCT
  			GCAGTCTGAAGATTTTGCTGTTTATTACTGTCAG
  			CAGTATAATAACTGGCCGTGGACGTTCGGCCAA
  			GGGACCAAGGTGGAATTCAAACGA
  67F5	VL32	440	GAAATAGTGATGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGAAAGAGTCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAG
  			CCTGGTACCAGCAGAAACCTGGCCAGGCTCCCA
  			GGCTCCTCATACATGGTTCATCCAACAGGGCCA
  			TTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGT
  			CTGGGACAGAGTTCACTCTCACCATCAGCAGCC
  			TGCAGTCTGCAGATTTTGCTGTTTATAACTGTCA
  			GCAGTATGAAATTTGGCCGTGGACGTTCGGCCA
  			AGGGACCAAGGTGGAAATCAAACGA
  64B10v1	VL33	441	CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG
  64B10v2			CGGCCCCAGGACAGAAGGTCACCATCTCCTGCT
  			CTGGAAGCAGCTCCAATATTGGGAATAATTATG
  			TAGCCTGGTACCAGCAGCTCCCAGGAACAGCCC
  			CCAAACTCCTCATTTATGACAATGATAAGCGAC
  			CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAA
  			GTCTGGCACGTCAGCCACCCTGGGCATCACCGG
  			ACTCCAGACTGGGGACGAGGCCGATTATTACTG
  			CGGAACATGGGATAGCAGCCTGAGTGCTGTGGT
  			ATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT
  68C8	VL34	442	CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG
  			CGGCCCCAGGACAGAAGGTCACCATCTCCTGCT
  			CTGGAAGCAGTTCCAACATTGGAAATAATTATG
  			TATCCTGGTACCAGCAGCTCCCAGGAACAGCCC
  			CCAAACTCCTCATTTATGACAATAATAAGCGAC
  			CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAA
  			GTCTGGCACGTCAGCCACCCTGGGCATCACCGG
  			ACTCCAGACTGGGGACGAGGCCGATTATTACTG
  			CGGAACATGGGATAGCAGCCTGAGTGCTGTGGT
  			ATTCGGCGGAGGGACCAAACTGACCGTCCTAGGT
  67A5	VL35	443	GATATTGTGATGACCCAGACTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGA
  			TGGAAATACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAACTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCACTGGGTCAGGCACTGAATTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTCTAGAGTTT
  			CCTATTACCTTCGGCCAAGGGACACGACTGGAG
  			ATTAAACGA
  67C10	VL36	444	GATTTTGTGATGACCCAGACTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGA
  			TGGAAACACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAGCTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTATAGAGTTT
  			CCTATCACCTTCGGCCAAGGGACACGACTGGAG
  			ATTAAACGA
  64H6	VL37	445	TCCTACGAGCTGACTCAGCCACTCTCAGTGTCAG
  			TGGCCCTGGGACAGACGGCCAGGATTACCTGTG
  			GGGGAAACAACATTGGAAGTAAAAATGTGCACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGG
  			TGGTCATCTATAGGGATAGCAAGCGGCCCTCTG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCGG
  			GGAACACGGCCACCCTGACCATCAGCAGAGCCC
  			AAGCCGGGGATGAGGCTGACTATTACTGTCAGG
  			TGTGGGACAGCAGTCCTGTGGTATTCGGCGGAG
  			GGACCAAGCTGACCGTCCTAGGT
  63F9	V L38	446	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGTATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGACATTAGAAATGATTTAG
  			CCTGGTATCAGCAGACACCAGGGAAAGCCCCTA
  			AGCGCCTGATCTATGCTTCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCACTGGATC
  			TGGGACAGAATTCACTCTCACAATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTTCTGTCTA
  			CAGCGTAATAGTTACCCGCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  67F6v1	VL39	447	GATATTGTAATGACCCAGACCCCACTCTCCCTGC
  			CCGTCATCCCTGGAGAGCCGGCCTCCATCTTCTG
  			CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGC
  			TGGTACCACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAACTCCTGATCTATAC
  			GCTTTCCTTTCGGGCCTCTGGAGTCCCAGACAGG
  			TTCAGTGGCAGTGGGTCAGGCACTGATTTCACA
  			CTGAAAATCACTAGGGTGGAGGCTGAGGATGTT
  			GGAGTTTATTATTGCATGCAACGTATAGAGTTCC
  			CTATCACCTTCGGCCAAGGGACACGACTGGAGA
  			TTAAACGA
  67F6v2	VL108	1864	GATATTGTAATGACCCAGACCCCACTCTCCCTGC
  			CCGTCATCCCTGGAGAGCCGGCCTCCATCTTCTG
  			CAGGTCTAGTCAGAGCCTCTTAAATAGTGATGC
  			TGGTACCACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCGGTCTCCACAACTCCTGATCTATAC
  			GCTTTCCTTTCGGGCCTCTGGAGTCCCAGACAGG
  			TTCAGTGGCAGTGGGTCAGGCACTGATTTCACA
  			CTGAAAATCACTAGGGTGGAGGCTGAGGATGTT
  			GGAGTTTATTATTGCATGCAACGTATAGAGTTCC
  			CTATCACCTTCGGCCAAGGGACACGACTGGAGA
  			TTAAACGA
  48C9	VL78	448	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  49A12			CTGCATCTATAGGAGACAGAGTCACCATCACTT
  51E2			GCCGGGCAAGTCAGAACATTAGGACCTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATTTATGTTGCATCCAGTTTGGAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCACTGGATC
  			TGGGACAGATTTCGCTCTCACCATCAGCAGTCTC
  			CAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGAGTGACAGTATCCCTCGGACGTTCGGCCAAG
  			GGACCAAGGTGGAAATCAAACGA
  48F3	VL77	449	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGGATTAGCAGTTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGTTCTTGATATATGCTGTATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			GAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGAGTTACAGTGCTACATTCACTTTCGGCCCTGG
  			GACCAAAGTGGATATCAAACGA
  48F8	VL49	450	GAAATTGTGCTGACTCAGTCTCCAGACTTTCAGT
  53B9			CTGTGACTCCAAAGGAGAAAGTCACCATCACCT
  56B4			GCCGGGCCAGTCAGGACATTGGTAATAGCTTAC
  57E7			ACTGGTACCAGCAGAAACCAGATCAGTCTCCAA
  57F11			AGCTCCTCATCAAGTTTGCTTCCCAGTCCTTCTC
  			AGGGGTCCCCTCGAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCGCCCTCACCATCAATAGCCT
  			GGAAGCTGAAGATGCTGCAACGTATTACTGTCA
  			TCAGAGTAGTGATTTACCGCTCACTTTCGGCGGA
  			GGGACCAAGGTGGACATCAAACGA
  48H11	V L40	451	GACATCCAGATGACCCAGTCTCCATCCTCTCTGT
  			CTACATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAACATTAGGAGCTATTTAA
  			ATTGGTATCAACTGAAACCAGGGAAAGCCCCTA
  			AGGTCCTGATCTATGGTGCATCTAATTTACAGAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAATCTG
  			CAATCTGAAGATTTTGCAATTTACTACTGTCAAC
  			AGAGTTACAATACCCCGTGCAGTTTTGGCCAGG
  			GGACCAAGCTGGAGATCAAACGA
  49A10	V L65	452	GATATTGTGATGACCCAGACTCCACTCTCCCTGC
  48D4			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGA
  			TGGAAACACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAGCTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTATAGAGTTT
  			CCGATCACCTTCGGCCAAGGGACACGACTGGAG
  			ATTAAACGA
  49C8	VL45	453	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  52H1			CTGCATCTGTAGGAGACAGAGTCACCTTCACTT
  			GCCAGGCGAGTCAGGACATTAACATCTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTACGATGTATCCAATTTGGAAAC
  			AGGGGTCCCATCAAGGTTCAGTGGAAGTGGATC
  			TGGGACAGATTTTACTTTCACCATCAGCAGCCTG
  			CAGCCTGAAGATATTGCAACATATTTCTGTCAAC
  			AATATGATAATCTCCCATTCACTTTCGGCCCTGG
  			GACCAAAGTGGATCTCAAACGA
  49G2	V L66	454	GATATTGTGTTGACCCAGACTCCACTCTCCCTGC
  50C12			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  55G11			CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGA
  			TGGAGACACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAGCTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACATATAGAATTT
  			CCTTCGACCTTCGGCCAAGGGACACGACTGGAG
  			ATTAAACGA
  49G3	VL47	455	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTATAGGAGACAGAGTCACCATCACTT
  			GCCAGGCGAGTCAGGGCATTAGCAACTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTACGATGCATCCAATTTGGAAA
  			CAGGGGTCCCATCAAGGTTCAGTGGAAGTGGAT
  			CTGGGACAGATTTTACTTTCACCATCAGCAGCCT
  			GCAGCCTGAAGATATTGCTACATATTACTGTCAC
  			CAGTATGATGATCTCCCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCAGACGA
  49H12	V L43	456	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCAGGCGAGTCAAGACATTACCAAATATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTACGATACATTCATTTTGGAAAC
  			AGGGGTCCCATCAAGGTTCAGTGGAAGTGGATC
  			TGGGACAGATTTTACTTTCACCATCAGCAGCCTG
  			CAGCCTGAAGATATTGCAACATATTACTGTCAA
  			CAGTATGACAATTTACCGCTCACCTTCGGCCAA
  			GGGACACGACTGGAGATTAAACGA
  51A8	VL61	457	AATTTTATACTGACTCAGCCCCACTCTGTGTCGG
  			AGTCTCCGGGGAAGACGGTAACCATCTCCTGCA
  			CCCGCAGCAGTGGCAGCATTGCCAGCGACTATG
  			TGCAGTGGTACCAGCAGCGCCCGGGCAGTTCCC
  			CCACCACTGTGATCTATGAGGATAAAGAAAGAT
  			CCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCAT
  			CGACAGTTCCTCCAACTCTGCCTCCCTCACCATC
  			TCTGGACTGAAGACTGAGGACGAGGCTGACTAC
  			TACTGTCAGTCTTATGATCGCAACAATCATGTGG
  			TTTTCGGCGGAGGGACCAAGCTGACCGTCCTAG
  			GT
  51C10.1	VL55	458	TCCTATGAGTTGACACAGCCGCCCTCGGTGTCTG
  			TGTCCCCAGGCCAAACGGCCAGGATCACCTGCT
  			CTGGAGATGCATTGCCAAAAAAATATGCTTATT
  			GGTACCAGCAGAAGTCAGGCCAGGCCCCTGTGC
  			TGGTCATCTATGAGGACAGCAAACGACCCTCCG
  			GGATCCCTGAGAGATTCTCTGGCTCCATCTCAGG
  			GACAATGGCCACCTTGACTATCAGTGGGGCCCA
  			GGTGGAGGATGAAGCTGACTACTACTGTTACTC
  			AACAGACAGCAGTGTTAATCATGTGGTATTCGG
  			CGGAGGGACCAAGCTGACCGTCCTAGGT
  51C10.2	V L70	459	TCCTATGACCTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAGACGAATTGGGGGATAAATATGCTTGCT
  			GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTGC
  			TGGTCATCTATCAAGATACCAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTATGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCGGCACTGTGGTATTCGGCGGAGG
  			GACCAAACTGACCGTCCTAGGT
  51E5	VL79	460	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGACATTAGAAATGATTTAG
  			GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			ACCGCCTGATCTATGCTGCATCCAGTTTGCAATT
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGAATTCACTCTCACAATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTACTGTCTA
  			CAACATAGTAGTTACCCGCTCACTTTCGGCGGA
  			GGGACCAGGGTGGAGATCAAACGA
  51G2	VL51	461	GACATCCAGATGACCCAGTCTCCATCTTCCGTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCAGGGTATTAGCAGCTGGTTAG
  			CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTATGATGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTACTATTGTCAA
  			CAGACTAACAGTTTCCCTCCGTGGACGTTCGGCC
  			AAGGGACCAAGGTGGAAATCAAACGA
  52A8	VL41	462	GACATCCAGATGACCCAGTCTCCATCCTTCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGACTATTAGCAGTTATTTAA
  			ATTGGCATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCAGTCTCACCATCAGCAGTCT
  			GCAACCTGAAGATTTTGCAACTTACTACTGTCAG
  			CAGAGTTACAGTACCCCGCTCACTTTCGGCGGC
  			GGGACCAAGGTGGAGATCAAACGA
  52B8	VL82	463	GAAGTTGTGCTGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGGAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCGACATCTTAG
  			CCTGGTACCAACAGAAACCTGGCCAGGCTCCCA
  			GGCTCCTCATCTATGGTGCATCCACCAGGGCCA
  			CTGGTATCCCAGCCAGGTTCAGTGGCGGTGGGT
  			CTGGGACAGAGTTCACTCTCACCATCAGTAGCC
  			TGCAGTCTGAAGATTTTGCAGTTTATTTCTGTCA
  			GCAGTATAATAACTGGCCGCTCACTTTCGGCGG
  			AGGGACCAAGGTGGAGATCAAACGA
  52C1	VL67	464	CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG
  			CGGCCCCAGGACAGAAGGTCACCATCTCCTGCT
  			CTGGAAGCAGCTCCAACATTGGGATTAATTATG
  			TATCCTGGTACCAGCAGCTCCCAGGAACAGCCC
  			CCAAACTCCTCATTTATGACAATAATAAGCGAC
  			CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAA
  			GTCTGGCACGTCAGCCACCCTGGGCATCACCGG
  			ACTCCAGACTGGGGACGAGGCCGATTATTGCTG
  			CGGAACATGGGATAGCAGCCTGAGTGCTGTGGT
  			ATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT
  52F8	VL42	465	GATATTGTGATGACTCAGTCTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCCTGCATAGTAATGG
  			ATACAACTATTTGGATTGGTACCTGCAGAAGCC
  			AGGGCAGTCTCCACAGCTCCTGATCTATTTGGGT
  			TCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC
  			AGTGGCAGGGGGTCAGGCACAGATTTTTCACTG
  			AAAATCAGCAGAGTGGAGGCTGAGGATGTTGGG
  			ATTTATTACTGCATGCAAGCTCTACAAACTCCAT
  			TCACTTTCGGCCCTGGGACCAATGTGGATATCA
  			AACAA
  52H2	VL84	466	GAAAATGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCTT
  			GTAGGGCCAGTCAGAGTGTTAGAAGCAGCTACT
  			TAGCCTGGTACCAGCAGAGACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTTTGGTGCATCCAGGAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTAGTTCACCTCGCAGTTTTGG
  			CCAGGGGACCAAGCTGGAGATCAAACGA
  53F6	VL63	467	GATATTGTGATGACTCAGTCTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCCAGCATAGTAATGG
  			ATACAACTATTTGGATTGGTACCTGCAGAAGCC
  			AGGACAGTCTCCACAGTTATTGATCTATTTGGAT
  			TCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC
  			AGTGGCAGTGGATCAGGCACAGATTTTACACTG
  			AAAATCAGCAGAGTGGAGGCTGAGGATATTGGG
  			GTTTATTACTGCATGCAAGGTCTACAAACTCCTC
  			CCACTTTCGGCGGAGGGACCAAGGTGGAGATCA
  			AACGA
  53H5.2	VL62	468	GACATCCAGATGACCCAGTCTCCATCTTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGGGCATTAGAAATGATTTAG
  			GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCGCCTGATCTATGCTGCATCCAGTTTGCAAA
  			GTGGGGTCCCATCAAGGTTCAGCGGCAGCGGAT
  			CTGGGACAGAATTCACTCTCACAATCAGCAGCC
  			TGCAGCCTGAAGATTTTGCAACTTATTACTGTCT
  			ACAGCATAAGAGTTACCCATTCACTTTCGGCCCT
  			GGGACCAAAATGGATATCAAAGGA
  53H5.3	V L80	469	GAAATAGTGATGACGCAGTCTCCAGTCACCTTG
  			TCTGTGTCTCCAGGGGAAAGAGCCATCATCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGCAACGTCG
  			CCTGGTACCAGCAGAAACCTGGCCAGACTCCCA
  			GGCTCCTCATCTATGGTGCATCCACCAGGGCCA
  			CTGGTCTCCCAACCAGGTTTAGTGGCAGTGGGT
  			CTGGGACAGTGTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAGTTTATTACTGTCAG
  			CAGTTTAGTAACTCAATCACCTTCGGCCAAGGG
  			ACACGACTGGAGATTAAACGA
  54A1	VL44	470	GACATCCAGATGGCCCAGTCTCCATCCTCCCTGT
  55G9			CTGCATCTGTTGGAGACAGAGTCACCATCACTT
  			GCCAGGCGAGTCAGGACATTAGCATCTATTTAA
  			ATTGGTATCAGCTGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTACGATGTATCCAATTTGGAAAC
  			AGGGGTCCCATCAAGGTTCAGTGGAGGTGGATC
  			TGGGACAGATTTTACTTTCACCATCAGCAGCCTG
  			CAGCCTGAAGATATTGCAACATATTACTGTCAA
  			CAGTATGATAATCTCCCTCTCACTTTCGGCCCTG
  			GGACCAAAGTGGATATCAAACGA
  54H10.1	V L53	471	GAAATTGTGGTGACGCAGTCTCCAGGCACCCTG
  55D1			TCTTTGTCTGTAGGGGAAAGAGCCATCCTCTCCT
  48H3			GCAGGGCCAGTCAGAGTTTTAGCAGCAGTTACT
  53C11			TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAGCAGGG
  			CCACTGGCATCCCAGACAGGTTCAGCGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGTA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTAGCTCACGGACGTTCGGCC
  			AAGGGACCAAGGTGGAAATCAAACGA
  55D3	V L71	472	GACATCCAGATGACCCAGTCTCCATCCTCACTGT
  			CTGTATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCAGGACATTAGCAATTATTTAG
  			CCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTA
  			AGTCCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAAGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTACTGCCAA
  			CAGTATAATATTTACCCTCGGACGTTCGGCCAA
  			GGGACCAAGGTGGAAATCAAGCGA
  55E4	VL75	473	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  49B11			CTACATCTATAGGAGACAGAATCACCATCACTT
  50H10			GCCGGGCAAGTCAGAGCATTAGTAACTATTTAA
  53C1			ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA
  			GGCTCCTGATCTATACAGCTTCCAGTTTGCAAAG
  			TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG
  			GGACCAAGGTGGAAATCAAACGA
  55E9	VL68	474	GATATTGTGATGACTCAGTCTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCCTGCATAGTAACGG
  			ATTCAACTATTTGGATTGGTACCTGCAGAAGCC
  			AGGGCAGTCTCCACAGGTCCTGATCTATTTGGGT
  			TCTAATCGGGCCTCCGGGGTCCCTGACAGGTTC
  			AGTGGCAGTGGATCAGGCACAGATTTTACACTG
  			AAAATCAGCAGAGTGGAGGCTGAGGATGTTGGG
  			ATTTATTACTGCATGCAAGCTCTACAAACTCTCA
  			TCACCTTCGGCCAAGGGACACGACTGGAGATTA
  			AACGA
  55G5	VL83	475	TCCTATGAACTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAGATAATTTGGGGGATAAATATGCTTTCT
  			GGTATCAACAGAAGCCAGGCCAGTCCCCTGTAT
  			TGGTCATCTATCAAGATAACAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTGTGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCGCCACTGTGATTTTCGGCGGAGG
  			GACCAAGTTGACCGTCCTAGGT
  56A7	V L52	476	GACATCCAAATGACCCAGTCTCCATCTTCCGTGT
  56E4			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCAGGATATTAGCAGTTGGTTAG
  			CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AATTCCTGATCTATGATGCATCCACTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGGCAGATTTCACTCTCACCATCAACAACCT
  			GCAGCCTGAAGATTTTGCAACTTACTATTGTCAA
  			CAGACTAACAGTTTTCCTCCGTGGACGTTCGGCC
  			AAGGGACCAAGGTGGAAATCAAACGA
  56C11	VL64	477	TCCTATGTGCTGACTCAGCCACCCTCGGTGTCAG
  			TGGCCCCAGGACAGGCGGCCAGGATTACCTGTG
  			GGGGAAACGACATTGGAAGTAAAAGTGTGCACT
  			GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGC
  			TGGTCGTCTATGATGATAGCGACCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAAGTCTGG
  			GAACACGGCCACCCTGATTATCAGCAGGGTCGA
  			AGCCGGGGAAGAGGCCGACTATTATTGTCAGGT
  			GTGGGATAGTAGTAGTGATGTGGTATTCGGCGG
  			AGGGACCAAGTTGACCGTCCTAGGT
  56E7	VL86	478	GACCTCCAGATGACCCAGTCTCCTTCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCAGGCGAGTCAGGACATTAAAAAATTTTTAA
  			ATTGGTATCAGCAGAAACCAGGTAAAGCCCCTA
  			ACCTCCTGATCTACGATGCATCCAATTTGGAAAC
  			AGGGGTCCCATCAAGGTTCAGTGGAAGTGGATC
  			TGGGACAGATTTTACTTTCACCATCAGCAGCCTG
  			CAGCCTGAAGATATTGCAACATATTACTGTCAA
  			CAATATGCTATTCTCCCATTCACTTTCGGCCCTG
  			GGACCACAGTGGATATCAAACGA
  56G1	VL76	479	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGCATTAGCAACTATTTAA
  			ATTGGTTTCTGCAGATACCAGGGAAAGCCCCTA
  			AACTCCTGATCTATGCAGCTTCCAGTTTACAAAG
  			TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAACAGTCTG
  			CAACCTGAAGATTTTGGAACTTACTACTGCCAA
  			CAGAGTTCCACTATCCCTTGGACGTTCGGCCAA
  			GGGACCAAGGTGGAAATCAAACGA
  56G3.3	V L81	480	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  55B10			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGAGACTACT
  			TAGCCTGGTATCGGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCGTCTATGGTGCATCCGCCAGGG
  			CCACTGGCATCCCAGACAGATTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAATATGGTAGATCACTATTCACTTTCGG
  			CCCTGGGACCAAAGTGGATATCAAACGA
  57B12	V L72	481	GACATCCAGATGACCCAGTCTCCATCCTCACTGT
  			CTGTATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCATGACATTAGCAATTATTTAG
  			CCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTA
  			AGTCCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAAGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTACTGCCAA
  			CAATATAATACTTACCCTCGGACGTTCGGCCAA
  			GGGACCAAGGTGGAAATCAAGCGA
  57D9	VL87	482	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCCGAGTGTTAGCAGCAGCTACT
  			TAGCCTGGTACCAGCAGAAACCTGCCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAGTAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCATCAGTATGGTACCTCACCGTGCAGTTTTGG
  			CCAGGGGACCAAGCTGGAGATCAAACGA
  59A10	VL48	483	GACATCCAGATGACCCAGTCTCCATCTTCCGTGT
  49H4			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GTCGGGCGAGTCAGGGTATTAGCAGCTGGTTAG
  			CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AACTCCTGATCTATGGTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTATTGTCAA
  			CAGACTAACAGTTTCCCTCCGTGGACGTTCGGCC
  			AAGGGACCAAGGTGGAAATCAAACGA
  59C9	V L50	484	GACATCCAGATGACCCAGTCTCCATCTTCCGTGT
  58A5			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  57A4			GTCGGGCGAGTCAGGATATTGACAGCTGGTTAG
  57F9			TCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			ACCTCCTGATCTATGCTGCATCCAATTTGCAAAG
  			AGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCGCCAGCCTG
  			CAGCCTGAAGATTTTGCAACTTACTATTGTCAGC
  			AGACTAACAGTTTCCCTCCGTGGACGTTCGGCC
  			AAGGGACCAAGGTGGAAATCAAACGA
  59G10.2	V L60	485	TCCTATGAGCTGTCTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGTCAGCATCACCTGCT
  			CTGGAGATAATTTGGGGGATAAATATGCTTGCT
  			GGTATCAGCAGAGGCCAGGCCAGTCCCCTGTCC
  			TGGTCATCTATCAAGATACCAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAATTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTATGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCAGCACTACATGGGTGTTCGGCGG
  			AGGGACCAAGCTGACCGTCCTAGGT
  59G10.3	VL54	486	CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTG
  			CGGCCCCAGGACAGAAGGTCACCATCTCCTGCT
  			CTGGAAGCAGCTCCAACATTGGGGATAATTATG
  			TATCCTGGTACCAGCAGTTCCCAGGAACAGCCC
  			CCAAACTCCTCATTTATGACAATAATAAGCGAC
  			CCTCAGGGATTCCTGACCGATTCTCTGGCTCCAA
  			GTCTGGCACGTCAGCCACCCTGGGCATCACCGG
  			ACTCCAGACTGGGGACGAGGCCGATTATTACTG
  			CGGAACATGGGACAGCAGCCTGAGTGTTATGGT
  			TTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT
  60D7	VL69	487	GATATTGTGCTGACCCAGACTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCTTGGATAGTGATGA
  			TGGAGACACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAGCTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTATAGAGTTT
  			CCGCTCACTTTCGGCGGAGGGACCAAGGTGGAG
  			ATCAAACGA
  60F9	VL58	488	GAAATTATGTTGACGCAGTCTCCAGGCACCCTG
  48B4			TCTTTGTCTCCAGGGGAAAGGGCCACCCTCTCCT
  52D6			GCAGGGCCAGTCAGAGGGTTCCCAGCAGCTACA
  			TAGTCTGGTACCAGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTTCATCCAACAGGGC
  			CACTGGCATCCCAGACAGGTTCAGTGGCAGTGG
  			GTCTGGGACAGACTTCACTCTCACCATCGGCAG
  			ACTGGAGCCTGAAGATTTTGCAGTGTACTACTGT
  			CAGCAGTATGGTAGCTCACCTCCGTGGACGTTC
  			GGCCAAGGGACCAAGGTGGCAATCAAACGA
  60G5.2	VL46	489	TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAAATAAATTGGGGGATAAATATGTTTGCT
  			GGTATCAGCAGAAGCCAGGCCAGTCCCCTGTCT
  			TGGTCATCTATCAAGATAGCAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTTTGGATGAGGCTGACTATTACTGTCAGGC
  			GTGGGACAGCAGCACTTGGGTGTTCGGCGGAGG
  			GACCAAGCTGACCGTCCTAGGT
  61G5	VL59	490	GAAATTATGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGAGTTCCCAGCAGCTACT
  			TAGTCTGGTACCAGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAACAGGG
  			CCACAGGCATCCCAGACAGGTTCAGCGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCGGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTAGTTCACCTCCGTGGACGTT
  			CGGCCAAGGGACCAAGGTGGCAATCAAACGA
  52C5	V L73	491	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTATAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGCATTAGCAACTATTTAA
  			ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA
  			GGCTCCTGATCTATGCAGCTTCCAGTTTGCAAAG
  			TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTGCAATTTACTACTGTCAAC
  			AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG
  			GGACCAAGGTGGAAATCAAACGA
  61H5	VL88	492	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  52B9			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGCAGAGACTACT
  			TAGCCTGGTACCGGCAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAGCAGGG
  			CCACTGGCATCCCAGACAGATTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAATATGGTAGATCACTATTCACTTTCGG
  			CCCTGGGACCACAGTGGATATCAAACGA
  59D10v1	V L56	493	TCCTATGAGCTGACACAGCCACCCTCGGTGTCTG
  			TGTCCCCAGGCCAAACGGCCAGGATCACCTGCT
  			CTGGAGATGCAGTGCCAAAAAAATATGCTAATT
  			GGTACCAGCAGAAGTCAGGCCAGGCCCCTGTGC
  			TGGTCATCTATGAGGACAGCAAACGACCCTCCG
  			GGATCCCTGAGAGATTCTCTGGCTCCAGCTCAG
  			GGACAATGGCCACCTTGACTATCAGTGGGGCCC
  			AGGTGGAGGATGAAGCTGACTACTACTGTTACT
  			CAACAGACAGCAGTGGTAATCATGTGGTATTCG
  			GCGGAGGGACCAAGCTGACCGTCCTAGGT
  59D10v2	VL57	494	TCCTATGAGTTGACTCAGCCACCCTCAGTGTCCG
  			TGTCCCCAGGACAGACAGCCAGCATCACCTGCT
  			CTGGAGATAAATTGGGGGATAAATACGTTTGCT
  			GGTATCAGCAGATGCCAGGCCAGTCCCCTGTGT
  			TGGTCATCCATCAAAATAACAAGCGGCCCTCAG
  			GGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG
  			GAACACAGCCACTCTGACCATCAGCGGGACCCA
  			GGCTATGGATGAGGCTGACTATTATTGTCAGGC
  			GTGGGATAGTAGTACTGCGGTATTCGGCGGAGG
  			GACCAAGCTGACCGTCCTAGGT
  56G3.2	V L85	495	GAAACAGTGATGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGGCAGAGTGTTGGCAGTAACTTAA
  			TCTGGTACCAGCAGAAACCTGGCCAGGCTCCCA
  			GGCTCCTCATCTTTGGTGCATCCAGCAGGGACA
  			CTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGT
  			CTGGGACAGAGTTCACTCTCACCATCAGCAGCC
  			TGCAGTCTGAAGATTTTGCAGTTTATTACTGTCA
  			GCAGTATAATAATTGGCCTCTCACTTTCGGCGGA
  			GGGACCAAGGTGGAGATCAAACGA
  66F7	V L7	496	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGACAAGTCAGAGCATTAGCAACTATTTAA
  			ATTGGTATCAGCAGAAACCAGGAAAAGCCCCTA
  			ACCTCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGATTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCGGTCTG
  			CAACCTGAGGATTTTTCAACTTACTACTGTCAAC
  			AGAGTTACAGTACCTCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCAAACGA
  48G4	VL89	497	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  53C3.1			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTGCCAGCAGTTACT
  			TAGTCTGGTACCAACAGAAACCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATTCAGCAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGGA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTACCTCACCATTTACTTTCGG
  			CCCTGGGACCAAAGTGGATCTCAAACGA
  50G1	V L90	498	GACATTGTGATGACCCAGACTCCACTCTCCCTGC
  			CCGTCAGCCCTGGAGAGCCGGCCTCCATCTCCT
  			GCAGGTCTAGTCAGAGCCTCTTGGATAGTGATG
  			ATGGAGACACCTATTTGGACTGGTACCTGCAGA
  			AGCCAGGGCAGTCTCCACAGCTCCTGATCTATA
  			CGCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGTCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTATAGAGTTT
  			CCGCTCACTTTCGGCGGAGGGACCAAGGTGGAG
  			ATCAAACGA
  58C2	VL91	499	GAAATTGTGATGACCCAGACTCCACTCTCCCTGC
  			CCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAGAGCCTCTTCGATAATGATGA
  			TGGAGACACCTATTTGGACTGGTACCTGCAGAA
  			GCCAGGGCAGTCTCCACAACTCCTGATCTATAC
  			GCTTTCCTATCGGGCCTCTGGAGTCCCAGACAG
  			GTTCAGTGGCAGTGGGTCAGGCACTGATTTCAC
  			ACTGAAAATCAGCAGGGTGGAGGCTGAGGATGT
  			TGGAGTTTATTACTGCATGCAACGTTTAGAGTTT
  			CCGATCACCTTCGGGCAAGGGACACGACTGGAG
  			ATTAAACGA
  60G5.1	V L74	1865	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTATAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGCATTAGCAACTATTTAA
  			ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA
  			GGCTCCTGATCTATGCAGCTTCCAGTTTGCAAAG
  			TGGGGTCCCATCGAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG
  			GGACCAAGGTGGAAATCAAACGA
  50D4	VL92	500	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCGAGTCAGGACATTAGCAATTATTTAG
  			CCTGGTATCAGCAGAAACCAGGGAAAGTTCCTA
  			CGCTCCTGATCTATGCTGCATCCACTTTGCTATC
  			AGGGGTCCCATCTCGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGCCT
  			GCAGCCTGAAGATGTTGCAGCTTATTACTGTCA
  			AAAGTATTACAGTGCCCCTTTCACTTTCGGCCCT
  			GGGACCAAAGTGGATATCAACCGA
  50G5v1	VL93	501	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACTATCACTT
  			GCCGGGCAAGTCAGGGCATTAGAAATGATTTAG
  			GCTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			ACCGCCTGATCTATGCTGCGTCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC
  			TGGGACAGAATTCACTCTCACAATCAGCAGCCT
  			GCAGCCTGAAGATTTTGCAACTTATTACTGTCTA
  			CAGCATAATAGTTACCCTCGGACGTTCGGCCAA
  			GGGACCAAGGTGGAAATCAAACGA
  50G5v2	VL94	502	GATGTTGTGATGACTCAGTGTCCACTCTCCCTGC
  			CCGTCACCCTTGGACAGCCGGCCTCCATCTCCTG
  			CAGGTCTAGTCAAAGACTCGTATACAGTGATGG
  			AAACACCTACTTGAATTGGGTTCAGCAGAGGCC
  			AGGCCAATCTCCAAGGCGCCTAATTTATAAGGT
  			TTCTAACTGGGACTCTGGGGTCCCAGACAGATT
  			CAGCGGCAGTGGGTCAGGCACTGATTTCACACT
  			GAAAATCAGCAGGGTGGAGGCTGAGGATGTTGG
  			GGTTAATTACTGCATGGAAGGTACACACTGGCC
  			TCGGGACTTCGGCCAAGGGACACGACTGGAGAT
  			TAAACGA
  51C1	VL95	503	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTATAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGCATTAGCAACTATTTAA
  			ATTGGTTTCAGCAGATCCCAGGGAAAGCCCCTA
  			GACTCCTGATCTATGCAGCTTCCAGTTTGCAAAG
  			TGGGGTCCCATCGAGGTTTAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGAGTTCCAGTATCCCTTGGACGTTCGGCCAAG
  			GGACCACGGTGGAAATCAAACGA
  53C3.2	VL96	504	GACATAGTGATGACGCAGTCTCCAGCCACCCTG
  			TCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTATTAGCAGCAATTTAG
  			CCTGGTACCAGCAGACACCTGGCCAGGCTCCCA
  			GGCTCCTCATCTATGGTACATCCATCAGGGCCA
  			GTACTATCCCAGCCAGGTTCAGTGGCAGTGGGT
  			CTGGGACAGAGTTCACTCTCACCATCAGCAGCC
  			TGCAGTCTGAAGATTTTGCAATTTATTACTGTCA
  			CCAGTATACTAACTGGCCTCGGACGTTCGGCCA
  			AGGGACCAAGGTGGAAATCAAACGA
  54H10.3	VL97	505	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGACCATTAGCATCTATTTAA
  			ATTGGTATCAGCAAAAACCAGGGAAAGCCCCTA
  			AGTTCCTGATCTATTCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTTCAACTTACTTCTGTCAAC
  			AGAGTTACAGTTCCCCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCAAACGA
  55A7	VL98	506	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTGTAGGAGACAGAGTCACCATCACTT
  			GCCGGGCAAGTCAGAGCATTAGCAGCTATTTAA
  			ATTGGTATCAGCAGAAACCAGGGAAAGCCCCTA
  			AGCTCCTGATCTATGCTGCATCCAGTTTGCAAAG
  			TGGGGTCCCATCAAGGTTCAGTGGCAGTGGATC
  			TGGGACAGATTTCACTCTCACCATCAGCAGTCTG
  			CAACCTGAAGATTTTGCAACTTACTACTGTCAAC
  			AGACTTACAGTGCCCCATTCACTTTCGGCCCTGG
  			GACCAAAGTGGATATCAAACGA
  55E6	VL99	507	GAAATTGTGTTGACGCAGTCTCCAGGCACCCTG
  			TCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
  			GCAGGGCCAGTCAGAGTGTTAGTCGCAGCCACT
  			TAGCCTGGTACCAGCAGAACTCTGGCCAGGCTC
  			CCAGGCTCCTCATCTATGGTGCATCCAGCAGGG
  			CCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
  			GGTCTGGGACAGACTTCACTCTCACCATCAGCA
  			GACTGGAGCCTGAAGATTTTGCAGTGTATTACT
  			GTCAGCAGTATGGTAGTTCACCGTGGACGTTCG
  			GCCAAGGGACCAAGGTGGAAATCAAACGA
  61E1	V L100	508	GACATCCAGATGACCCAGTCTCCATCCTCCCTGT
  			CTGCATCTATTAGAGACCGAGTCACCATCACTTG
  			CCGGGCAAGTCAGAGCATTGGCACCTTTTTAAA
  			TTGGTATCAGCAGAAACCAGGGACAGCCCCTAA
  			GCTCCTGATCTATGCTGCGTCCAGTTTGCAAAGT
  			GGGGTCCCATCAAGGTTCAGTGGCAGTGGATCT
  			GGGACAGATTTCACTCTCACCATCAGCAGTCTA
  			CATCCTGAAGATTTTGCGTCTTACTATTGTCAAC
  			AGAGTTTCAGTACCCCGCTCACTTTCGGCGGAG
  			GGACCAAGGTGGAGATCACACGA

• TABLE 2D
  Coding Sequence for Antibody Variable Heavy (VH) Chains

  Contained		SEQ ID
  in Clone	Designation	NO.	Coding Sequence

  63E6	V H 6	509	CAGGTGCAGCTTATGCAGTCTGGGGCTGAGGTG
  66F7			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCGGCTACTATA
  			TGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATGAACCCTAATAGTG
  			GTGCCACAAAGTATGCACAGAAGTTTCAGGGCA
  			GGGTCACCATGACCAGGGACACGTCCATCAGCA
  			CAGCCTACATGGAGCTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTGCGAGAGAAC
  			TCGGTGACTACCCCTTTTTTGACTACTGGGGCCA
  			GGGAACCCTGGGCATCGTCTCCTCA
  66D4	V H17	510	CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTC
  			TCCTGCAGGGCTTCTGGGTACACCTTCACCGGCT
  			ACTATATACACTGGATGCGACAGGCC
  			CCTGGCCATGGGCTGGAGTGGATGGGATGGATC
  			AACCCTCCCAGTGGTGCCACAAACTAT
  			GCACAGAAGTTTCGGGGCAGGGTCGCCGTGACC
  			AGGGACACGTCCATCAGCACAGTCTAC
  			ATGGAACTGAGCAGGCTGAGATCTGACGACACG
  			GCCGTATATTACTGTGCGAGAGAGACT
  			GGAACTTGGAACTTCTTTGACTACTGGGGCCAG
  			GGAACCCTGGTCACCGTCTCCTCA
  66B4	V H10	511	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCATCTGGATACACCTTCACCGGCTACTATT
  			TGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTAACAGTG
  			GTGGCACAGACTATGCACAGAAGTTTCAGGGCC
  			GGGTCACCATGACCAGGGACACGTCCATCAGTA
  			CAGCCTACATGGAGCTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTGTGGGAGACG
  			CAGCAACTGGTCGCTACTACTTTGACAACTGGG
  			GCCAGGGAACCCTGGTCACCGTCTCCTCA
  65B1	VH18	512	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAGGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCGGCTACTTTA
  			TGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTAACAGTG
  			GTGCCACAAACTATGCACAGAAGTTTCACGGCA
  			GGGTCACCATGACCAGGGACACGTCCATCACCA
  			CAGTCTACATGGAGCTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTACGAGAGAAC
  			TGGGGATCTTCAACTGGTTCGACCCCTGGGGCC
  			AGGGAACCCTGGTCACCGTCTCCTCA
  65B4	V H20	513	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTG
  			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCGCCTTCAGTAGTTACGACA
  			TGCACTGGGTCCGCCAAGCTACAGGAAAAGGTC
  			TGGAGTGGGTCTCAACTATTGATACTGCTGGTG
  			ACGCTTACTATCCAGGCTCCGTGAAGGGCCGAT
  			TCACCATCTCCAGAGAAAATGCCAAGACCTCCT
  			TGTATCTTCAAATGAACAGCCTGAGAGCCGGGG
  			ACACGGCTGTGTATTACTGTACAAGAGATCGGA
  			GCAGTGGCCGGTTCGGGGACTTCTACGGTATGG
  			ACGTCTGGGGCCAAGGGACCGCGGTCACCGTCT
  			CCTCA
  67A4	VH19	514	GAGGTGCAGCTGGAGGAGTCTGGGGGAGGCTTG
  			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGGACCTACGAC
  			ATGCACTGGGTCCGCCAAGTTACAGGAAAAGGT
  			CTGGAGTGGGTCTCAGCTATTGGTATTGCTGGTG
  			ACACATACTATTCAGACTCCGTGAAGGGCCGAT
  			TCACCATCTCCAGAGAAAATGCCAAGAACTCCC
  			TGTATCTTCAAATGAACAGTCTAAGAGTCGGGG
  			ACACGGCTGTGTATTACTGTGCAAGAGATCGGA
  			GCAGTGGCCGGTTCGGGGACTACTACGGTATGG
  			ACGTCTGGGGCCAAGGGACCACGGTCACCGTCT
  			CCTCA
  63A10v1	VH21	515	GAGGTGCAGCTGGTGGAGTCTGGGGGAGACTTG
  63A10v2			GTAAAGCCTGGGGGGTCCCTTAGACTCTCCTGT
  63A10v3			GCAGTCTCTGGAATCACTTTCAGTAACGCCTGG
  			ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGG
  			CTGGAGTGGGTTGGCCGTATTAAAAGCAAAACT
  			GATGGTGGGACAACAGACTACGCTGCACCCGTG
  			AAAGGCAGATTCACCGTCTCAAGAGATGGTTCA
  			AAAAATACGCTGTATCTGCAAATGAACAGCCTG
  			AAAACCGAGGACACAGCCGTGTATTACTGTACC
  			ACAGATAGTAGTGGGAGCTACTACGTGGAGGAC
  			TACTTTGACTACTGGGGCCAGGGAACCCTGGTC
  			ACCGTCTCCTCA
  65H11v1	VH22	516	GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTTG
  65H11v2			GTAAAGCCTGGGGGGTCCCTTAGACTCTCCTGT
  			GCAGCCTCTGGATTCACTTTCAGTAACGCCTGGA
  			TGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTTGGCCGTATTATAGGCAAAACTG
  			ATGGTGGGACAACAGACTACGCTGCACCCGTGA
  			AAGGCAGATTCACCATTTCAAGAGATGATTCAA
  			AAAACACGCTGTATCTGCAAATGAACAGCCTGA
  			AAACCGAGGACACAGCCGTGTATTACTGTACCT
  			CAGATAGTAGTGGGAGCTACTACGTGGAGGACT
  			ACTTTGACTACTGGGGCCAGGGAACCCTGGTCG
  			CCGTCTCCTCA
  67G10v1	V H9	517	GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTTG
  67G10v2			GTAAAGCCGGGGGGGTCCCTTAGACTCGCCTGT
  			GCAGCCTCTGGAATCACTTTCAATAACGCCTGG
  			ATGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGG
  			CTGGAATGGGTTGGCCGTATTAAAAGCAAAACT
  			GATGGTGGGACAACAGACTACGCTGCACCCGTG
  			AAAGGCAGATTCACCATCTCAAGAGATGATTCA
  			AAAAGTATACTGTATCTGCAAATGAACAGCCTG
  			AAATCCGAGGACACAGCCGTGTATTATTGTACC
  			ACAGATAGTAGTGGGAGCTACTACGTGGAGGAC
  			TACTTTGACTACTGGGGCCAGGGAACCCTG
  			GTCACCGTCTCCTCA
  64C8	V H23	518	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GTAGCCTCTGGATTCACCTTCAGTAGCTATGGCA
  			TGCACTGGGTCCGCCAGGATCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAGTTATATCATATGATGGAA
  			GTAACAAACACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCTG
  			AGGACACGGCTGTGTATTACTGTGCGAGGGAAT
  			TACTATGGTTCGGGGAGTATGGGGTAGACCACG
  			GTATGGACGTCTGGGGCCAAGGGACCACGGTCA
  			CCGTCTCCTCA
  63G8v1	V H1	519	CAGGCGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  63G8v2			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  63G8v3			GCAGCCTCTGGATTCACCTTCAGTAGCTATGGCA
  68D3v1			TACACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  64A8			TGGAGTGGGTGGCAGTTATATCATATGATGGAA
  67B4			GTAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCTG
  			AGGACACGGCTGTGTATTACTGTGCGACTACGG
  			TGACTAAGGAGGACTACTACTACTACGGTATGG
  			ACGTCTGGGGCCAAGGGACCACGGTCACCGTCT
  			CCTCA
  68D3v2	VH95	1866	CAGGCGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTC
  			TCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCT
  			ATGGCATGCACTGGGTCCGCCAGGCT
  			CCAGGCAAGGGGCTGGAGTGGGTGGCATTTATA
  			TCATATGCTGGAAGTAATAAATACTAT
  			GCAGACTCCGTGAAGGGCCGATTCACCATCTCC
  			AGAGACAATTCCAAGAACACGCTGTAT
  			CTGCAAATGAGCAGCCTGAGAGCTGAGGACACG
  			GCTGTGTATTACTGTGCGACTACGGTG
  			ACTGAGGAGGACTACTACTACTACGGTATGGAC
  			GTCTGGGGCCAAGGGACCACGGTCACC
  			GTCTCCTCA
  66G2	V H11	520	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCAGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGGTATATCATATGATGGA
  			AGTAATAAAAACTATGCAGACTCCGTGAAGGGC
  			CGAATCACCATCTCCAGAGACAATCCCAAGAAC
  			ACGCTGTATCTGCAAATGAACAGCCTGAGAGCT
  			GAGGACACGGCTGTGTATTACTGTGCGACTACG
  			GTGACTAAGGAGGACTACTACTACTACGGTATG
  			GACGTCTGGGGCCAAGGGACCACGGTCACCGTC
  			TCCTCA
  65D1	V H26	521	CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTTACTATTACA
  			TTCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCACTTATATGGTATGATGGAA
  			GTAATAAAGACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCATGTGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGAAG
  			GGACAACTCGACGGGGATTTGACTACTGGGGCC
  			AGGGAACCCTGGTCACCGTCTCCTCA
  64H5	V H7	522	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGAGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGGATGATGGA
  			AGTAATAAATACTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGTCTCTGCAAATGAACAGCCTGAGGGCC
  			GAGGACACGGCTGTTTATTACTGTGCGAGAGAA
  			TACGTAGCAGAAGCTGGTTTTGACTACTGGGGC
  			CAGGGAACCCTGGTCACCGTCTCCTCA
  65D4	V H25	523	CAGGAGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGTGTCTGGATTCACCTTCAGTTTCTATGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAGTTATATGGTATGATGGAA
  			GTAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATTTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTACGAGAGCCC
  			TCAACTGGAACTTTTTTGACTACTGGGGCCAGG
  			GAACCCTGGTCACCGTCTCCTCA
  65E3	V	H24	524	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCCTCAGTAACTATAAC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTTTATGGTATGATGGA
  			AATACTAAATACTATGCAGACTCCGTGAAGGGC
  			CGAGTCACCATCTCTAGAGACAATTCCAAGAAC
  			ACGCTGTATCTTCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGAGAT
  			GTCTACGGTGACTATTTTGCGTACTGGGGCCAG
  			GGAACCCTGGTCACCGTCTCCTCA
  65G4	V H8	525	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGGATGATGGA
  			AGTAATAAATACTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGTCTCTGCAAATGAACAGCCTGAGGGCC
  			GAGGACACGGCTGTTTATTACTGTGCGAGAGAA
  			TACGTAGCAGAAGCTGGTTTTGACTACTGGGGC
  			CAGGGAACCCTGGTCACCGTCTCCTCA
  68G5	V H12	526	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			ACAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGTATGATGGA
  			AGTAATAAATACCATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACGATTCCAAGAAC
  			GCGCTTTATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGTGAGAGAT
  			CCTGGATACAGCTATGGTCACTTTGACTACTGGG
  			GCCAGGGAACCCTGGTCACCGTCTCCTCA
  67G8	V H27	527	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGTATGATGGA
  			AGTAATAAAGACTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGTATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGATCA
  			GCAGTGGCTTTGTACAACTGGTTCGACCCCTGG
  			GGCCAGGGAACCCTGGTCACCGTCTCCTCA
  65B7v1	VH28	528	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  65B7v2			GTGAACCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCAGCAGTGATGCTTA
  			CTACTGGAGCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTTTTACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATTTCAGTAGACACGTCTAAGAA
  			CCGGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGAG
  			TCTAGGATATTGTACTTCAACGGGTACTTCCAGC
  			ACTGGGGCCAGGGCACCCTGGTCACCGTCTCCT
  			CA
  63B6	V H4	529	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  64D4			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCG
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  			CTACTGGAGCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTATTACAG
  			TGGGACCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTAGACACGTCCAAGAA
  			CCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCC
  			GCGGACACGGCCGTATATTACTGTGCGAGAATG
  			ACTACTCCTTACTGGTACTTCGGTCTCTGGGGCC
  			GTGGCACCCTGGTCACTGTCTCCTCA
  63F5	V H13	530	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  			TTACTGGACCTGGATCCGCCAGCACCCAGGGAA
  			GGACCTGGAGTGGATTACATACATCTATTACAG
  			TGGGAGCGCCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTAGACACGTCTAAGAA
  			CCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC
  			GCGGACACGGCCGTATATTATTGTGCGAGGATG
  			ACTACCCCTTATTGGTACTTCGATCTCTGGGGCC
  			GTGGCACCCTGGTCACTGTCTCCTCA
  63H11	V H3	531	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  			CTACTGGACCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGCATACATCTATTACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTAGACACGTCTAAGAA
  			CCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC
  			GCGGACACGGCCGTATATTACTGTGCGAGGATG
  			ACTACCCCTTACTGGTACTTCGATCTCTGGGGCC
  			GTGGCACCCTGGTCACTGTCTCCTCA
  65E8	V H2	532	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  64E6			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC
  65F11			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  67G7			CTACTGGACCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGCATACATCTATTACAC
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTAGACACGTCTAAGAA
  			CCAGTTCTCCCTGAAGCTGAGCTCTGTGACTGCC
  			GCGGACACGGCCGTATATTACTGTGCGAGGATG
  			ACTACCCCTTACTGGTACTTCGATCTCTGGGGCC
  			GTGGCACCCTGGTCACTGTCTCCTCA
  65C1	V H15	533	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  			CTACTGGACCTGGATCCGCCAACACCCAGGGAA
  			GGGCCTGGAGTGGATTGCATACATTTTTTACAGT
  			GGGAGCACCTACTACAACCCGTCCCTCAAGAGT
  			CGAGTTACCATATCACTTGACACGTCTAAGAAC
  			CAGTTCTCCCTGAAGCTGAACTCTGTGACTGCCG
  			CGGACACGGCCGTATATTACTGTGCGAGGATGA
  			CTTCCCCTTACTGGTACTTCGATCTCTGGGGCCG
  			TGGCACCCTGGTCACTGTCTCCTCA
  66F6	V H14	534	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCC
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGATTA
  			CTACTGGACCTGGATCCGCCATCACCCAGGGAA
  			GGGCCTGGAGTGGATTGCATACATTTATTACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTTGACACGTCTAAGAA
  			CCAGTTTTCCCTGAAGCTGAACTCTGTGACTGCC
  			GCGGACACGGCCGTTTATTACTGTGCGAGGATG
  			ACTACCCCTTACTGGTACTTCGATCTCTGGGGCC
  			GTGGCACCCTGGTCACTGTCTCCTCA
  64A6	VH29	535	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTA
  			TTACTGGAGCTGGATCCGCCAGCGCCCAGGGAA
  			GGGCCTGGAGTGGGTTGGGTACATCTATTACAG
  			TGGGGGCACCCACTACAACCCGTCCCTCAAAAG
  			TCGAGTTACCATATCAATAGACACGTCTGAGAA
  			CCAGTTCTCCCTGAAGCTGAGTTCTGTGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGTC
  			CTCCATTACTCTGATAGTCGTGGTTACTCGTACT
  			ACTCTGACTTCTGGGGCCAGGGAACCCTGGTCA
  			CCGTCTCCTCA
  65F9	V H30	536	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTCTCTCTGGTGGCTCCTTCAGCAGTGGTGATTA
  			CTACTGGAGCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTATTACAG
  			TGGGAGCACCTACTACAACCCATCCCTCAAGAG
  			TCGAGTTACCATATCAATAGACACGTCTAAGAA
  			CCAGTTCTCCCTGAAACTGACCTCTGTGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGTC
  			CTCCATTACTATGATAGTAGTGGTTACTCGTACT
  			ACTTTGACTACTGGGGCCAGGGAACCCTGGTCA
  			CCGTCTCCTCA
  64A7	V H16	537	CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGCAGTGATACTT
  			CCTACTGGGGCTGGATCCGCCAGCCCCCAGGAA
  			AGGGGCTGGAGTGGATTGGGAATATCTATTATA
  			GTGGGACCACCTACTTCAACCCGTCCCTCAAGA
  			GTCGAGTCAGCGTATCCGTAGACACATCCAAGA
  			ACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGC
  			CGCAGACACGGCTGTGTTTTATTGTGCGAGACTC
  			CGAGGGGTCTACTGGTACTTCGATCTCTGGGGC
  			CGTGGCACCCTGGTCACTGTCTCCTCA
  65C3	V H5	538	CAGGTGCAGCTACAGGAGTCGGGTCCAGGACTG
  68D5			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACT
  			GGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
  			CTGGAGTGGATTGGGTATATCTATTACACTGGG
  			AGCACCAACTACAACCCCTCCCTCAAGAGTCGA
  			GTCACCATATCAGTAGACACGTCCAAGAACCAG
  			TTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGG
  			ACACGGCCGTGTATTACTGTGCGAGAGAATATT
  			ACTATGGTTCGGGGAGTTATTATCCTTGGGGCCA
  			GGGAACCCTGGTCACCGTCTCCTCA
  67F5	V H31	539	CAGGTGCAGCTGAAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTC
  			ACCTGCACTGTCTCTGGTGGCTCCATCAGTAGTT
  			ACTACTGGAGCTGGATCCGGCAGCCC
  			CCAGGGAAGGGACTGGAGTGGATTGGGTATATC
  			TATTACAGTGGGAACACCAACTACAAC
  			CCCTCCCTCAAGAGTCGAGTCACCATATCAGTA
  			GACACGTCCAAGAACCAGTTCTCCCTG
  			AAGCTGAGCTCTGTGACCGCTGCGGACACGGCC
  			GTGTATTACTGTGCGAGAGAATATTAC
  			TATGGTTCGGGGAGTTATTATCCTTGGGGCCAG
  			GGAACCCTGGTCACCGTCTCCTCA
  64B10v1	VH32	540	CAGATTCAGCTGCTGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCGTCAGTAGTGGTGATT
  			ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGA
  			AGGGACTGGAGTGGATTGGGTTTATCTATTACA
  			GTGGGGGCACCAACTACAACCCCTCCCTCAAGA
  			GTCGAGTCACCATATCAATAGACACGTCCAAGA
  			ACCAGTTCTCCCTGAAGCTGAACTCTGTGACCGC
  			TGCGGACACGGCCGTGTATTACTGTGCGAGATA
  			TAGCAGCACCTGGGACTACTATTACGGTGTGGA
  			CGTCTGGGGCCAAGGGACCACGGTCACCGTCTC
  			CTCA
  64B10v2	VH96	1867	CAGGTGCAGCTGCTGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCGTCAGCAGTGGTGATT
  			ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGA
  			AGGGACTGGAGTGGATTGGGTTTATTTATTACA
  			GTGGGGGCACCAACTACAACCCCCCCCTCAAGA
  			GTCGAGTCACCATATCAATAGACACGTCCAAGA
  			ACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGC
  			TGCGGACACGGCCGTGTATTACTGTGCGAGATA
  			TAGCAGCACCTGGGACTACTATTACGGTGTGGA
  			CGTCTGGGGCCAAGGGACCACGGTCACC
  			GTCTCCTCA
  68C8	VH33	541	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGACTCTGTCAGCAGTGGTGATA
  			ACTACTGGAGCTGGATCCGGCAGCCCCCAGGGA
  			AGGGACTGGAGTGGATTGGGTTCATGTTTTACA
  			GTGGGAGTACCAACTACAACCCCTCCCTCAAGA
  			GTCGAGTCACCATATCACTACACACGTCCAAGA
  			ACCAGTTCTCCCTGAGGCTGAGCTCTGTGACCGC
  			TGCGGACACGGCCGTGTATTACTGTGGGAGATA
  			TAGGAGTGACTGGGACTACTACTACGGTATGGA
  			CGTCTGGGGCCAAGGGACCACGGTCACCGTCTC
  			CTCA
  67A5	VH34	542	GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG
  			AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT
  			AAGGGTTCTGGATACAGCTTTACCAGTTACTGG
  			ATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGC
  			CTGGAGTGGATGGGGATCATCTATCCTGGTGAC
  			TCTGATACCAGATACAGCCCGTCCTTCCAAGGC
  			CAGGTCACCATCTCAGCCGACAAGTCCATCAAC
  			ACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCC
  			TCGGACACCGCCATATACTTCTGTGCGAGACGG
  			GCCTCACGTGGATACAGATTTGGTCTTGCTTTTG
  			CGATCTGGGGCCAAGGGACAATGGTCACCGTCT
  			CCTCA
  67C10	VH35	543	GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG
  			AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT
  			CAGGGTTCTGGATACAGCTTTAGCAGTTACTGG
  			ATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGC
  			CTGGAGTGGATGGGGATCATCTATCCTGGTGAC
  			TCTGATACCAGATACAGCCCGTCCTTCCAAGGC
  			CAGGTCACCATCTCAGCCGACAAGTCCATCAAT
  			ACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCC
  			TCGGACACCGCCATATATTACTGTGCGAGACGG
  			GCCTCACGTGGATACAGATATGGTCTTGCTTTTG
  			CTATCTGGGGCCAAGGGACAATGGTCACCGTCT
  			CTTCA
  64H6	VH36	544	GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG
  			AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT
  			AAGGGTTCTGGATACAGTTTTACCAGTTATTGGA
  			TCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCC
  			TGGAGTGGATGGGGATCATCTATCCTGGTGACT
  			CTGAAACCAGATACAGCCCGTCCTTTCAAGGCC
  			AGGTCACCATCTCAGCCGACAAGTCCATCAGCA
  			CCGCCTACCTGCAGTGGAACAGCCTGAAGACCT
  			CGGACACCGCCATGTATTTCTGTGCGACCGTAG
  			CAGTGTCTGCCTTCAACTGGTTCGACCCCTGGGG
  			CCAGGGAACCCTGGTCACCGTCTCCTCC
  63F9	VH37	545	CAGGTGCAGCTGAAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTA
  			CTACTGGAACTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTATGACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATGTCAGTAGACACGTCTAAGAA
  			CCAGTTCTCCCTGAAGTTGAGCTCTGTGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGAT
  			GTTCTAATGGTGTATACTAAAGGGGGCTACTAC
  			TATTACGGTGTGGACGTCTGGGGCCAAGGGACC
  			ACGGTCACCGTCTCCTCA
  67F6v1	V H38	546	GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTG
  67F6v2			AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT
  			AAGGGTTCTGGATACAGCTTTACCGGCTACTGG
  			ATCGGCTGGGTGCGCCAGCTGCCCGGGAAAGGC
  			CTGGAGTGGATGGGGATCATCTATCCTGGTGAC
  			TCTGATACCAGATACAGCCCGTCCTTCCAAGGC
  			CAGGTCACCATCTCAGTCGACAAGTCCATCAAC
  			ACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCC
  			TCGGACACCGCCATGTATTACTGTGCGAGACGG
  			GCCTCACGTGGATACAGCTATGGTCATGCTTTTG
  			ATTTCTGGGGCCAAGGGACAATGGTCACCGTGT
  			CTTCA
  48C9	V H73	547	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG
  49A12			TTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCT
  51E2			CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG
  			GACCTGGATCCGCCAGCCCCCAGGGAAGGGGCT
  			GGAGTGGATTGGGGAAATCAATCATAGTGAAAA
  			CACCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCAATAGACACGTCCAAGAACCAGTT
  			CTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGA
  			CACGGCTGTGTATTACTGTGCGAGAGAGAGTGG
  			GAACTTCCCCTTTGACTACTGGGGCCAGGGAAC
  			CCTGGTCACCGTCTCCTCA
  48F3	V H72	548	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACCG
  			TTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCG
  			CTGTCTATGGTGGGTCCATCAGTGGTTACTACTG
  			GAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCT
  			GGAGTGGATTGGGGAAATCACTCATACTGGAAG
  			CTCCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCAGTAGACACGTCCAAGAACCAGTT
  			CTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGA
  			CACGGCTGTGTATTACTGTGCGAGAGGCGGGAT
  			TTTATGGTTCGGGGAGCAGGCTTTTGATATCTGG
  			GGCCAAGGGACAATGGTCACCGTCTCTTCA
  48F8	VH48	549	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG
  53B9			GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  56B4			ACAGCCTCTGGATTCACCTTCAGAAGCTATAGC
  57E7			ATGAACTGGGTCCGCCAGGCTCCGGGGAAGGGG
  57F11			CTGGAGTGGGTCTCATCCATTAGTAGTAGTAGT
  			AGTTACGAATACTACGTAGACTCAGTGAAGGGC
  			CGATTCACCATCTCCAGAGACATCGCCAAGAGC
  			TCACTGTGGCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGATCC
  			CTAAGTATAGCAGTGGCTGCCTCTGACTACTGG
  			GGCAAGGGAACCCTGGTCACCGTCTCCTCA
  48H11	VH39	550	CAGGTGCAACTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCGGCTACTATA
  			AGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTAACAGTG
  			GTGCCACAAAGTATGCACAGAAGTTTCAGGGCA
  			GGGTCACCATGACCAGGGACACGTCCATCAGCA
  			CAGTGTACATGGAGCTGAGCAGGCTGAGATCTG
  			TCGACACGGCCCTGTATTACTGTGCGAGAGAGG
  			TACCCGACGGTATAGTAGTGGCTGGTTCAAATG
  			CTTTTGATTTCTGGGGCCAAGGGACAATGGTCA
  			CCGTCTCTTCA
  49A10	VH62	551	CAGGTGCACCTGGTGGAGTCTGGGGGAGGCGTG
  48D4			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAACTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAATTATATGGTATGATGGA
  			AGTAATAAAAACTATGCAGACTCCGTGAAGGGC
  			CGCTTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGTATCTGGAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGAGAT
  			CAGGATTACGATTTTTGGAGTGGTTATCCTTACT
  			TCTACTACTACGGTATGGACGTCTGGGGCCAAG
  			GGACCACGGTCACCGTCTCCTCA
  49C8	VH44	552	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  52H1			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCAGTTATGATA
  			TCGACTGGGTGCGACAGGCCACTGGACAAGGGC
  			TTGAGTGGATGGGATGGATGAACCCTAACGGTG
  			GTAACACAGGCTATGCACAGAAGTTCCAGGGCA
  			GAGTCACCATGACCAGGAACACCTCCATAAACA
  			CGGCCTATATGGAACTGAGCAGCCTGAGATCTG
  			AGGACACGGCCATATATTACTGTGCGAGAGGGA
  			AGGAATTTAGCAGGGCGGAGTTTGACTACTGGG
  			GCCAGGGAACCCTGGTCACCGTCTCCTCA
  49G2	VH63	553	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  50C12			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  55G11			GCAGCGTCTGGATTCACCTTCAGTAACTATGGC
  			ATGCGCTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCACTTATATGGTATGATGGA
  			AGTAATAAGTTCTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGAATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGAGAT
  			CGGTATTACGATTTTTGGAGTGGTTATCCATACT
  			TCTTCTACTACGGTCTGGACGTCTGGGGCCAAG
  			GGACCACGGTCACCGTCTCCTCA
  49G3	VH46	554	CAGGTCACCTTGAAGGAGTCTGGTCCTGTGCTG
  			GTGAAACCCACAGAGACCCTCACGCTGACCTGC
  			ACCGTCTCTGGGTTCTCACTCAGTAATCCTAGAA
  			TGGGTGTGAGCTGGATCCGTCAGCCCCCAGGGA
  			AGGCCCTGGAGTGGCTTACACACATTTTTTCGAA
  			TGACGAAAAATCCTACAGCACATCTCTGAAGAG
  			CAGGCTCACCATCTCCAAGGACACCTCCAAAAG
  			CCAGGTGGTCCTTTCCATGACCAACATGGACCCT
  			GTGGACACAGCCACATATTACTGTGTACGGGTA
  			GATACCTTGAACTACCACTACTACGGTATGGAC
  			GTCTGGGGCCAAGGGACCACGGTCACCGTCTCC
  			TCA
  49H12	VH42	555	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			ATGGCATCTGGATACATTTTCACCAGTTACGATA
  			TCAACTGGGTGCGACAGGCCACTGGACAAGGGC
  			CTGAGTGGATGGGATGGATGAACCCCTACAGTG
  			GGAGCACAGGCTATGCACAGAATTTCCAGGGCA
  			GAGTCACCATGACCAGGAATACCTCCATAAACA
  			CAGCCTACATGGAGCTGAGCAGCCTGAGATCTG
  			AGGACACGGCCGTGTATTACTGTGCGAAGTATA
  			ATTGGAACTATGGGGCTTTTGATTTCTGGGGCCA
  			AGGGACAATGGTCACCGTCTCTTCA
  51A8	VH58	556	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAGCTATGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAGTTATATCATATGATGGAA
  			GTAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGTTGTATCTGCAAATGAACAGCCTGAGAGCTG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGCGG
  			ACGGTGACTACCCATATTACTACTACTACTACGG
  			TATGGACGTCTGGGGCCAAGGGACCACGGTCAC
  			CGTCTCCTCA
  51C10.1	VH54	557	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG
  59D10v1			GTACAGCCGGGGGGGTCCCTGAGACTCTCCTGT
  59D10v2			GCAGCCTCTGGATTCACCTTTCGCAACTATGCCA
  			TGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCAGGTATTAGTGGTAGTAGTG
  			CTGGCACATACTACGCAGACTCCGTGAAGGGCC
  			GGTTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTTTCTGCAAATGGACAGCCTGAGAGCCG
  			AGGACACGGCCGTATATTACTGTGCGCAAGATT
  			GGAGTATAGCAGTGGCTGGTACTTTTGACTACT
  			GGGGCCAGGGAACCCTGGTCACCGTCTCCTCA
  51C10.2	VH67	558	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTA
  			CTACTGGAGCTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTATTACAA
  			TGGGAGTCCCTACGACAACCCGTCCCTCAAGAG
  			GCGAGTTACCATCTCAATAGATGCGTCTAAGAA
  			CCAGTTCTCCCTGAAGCTGAGCTCTATGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGGG
  			GCCCTCTACGGTATGGACGTCTGGGGCCAAGGG
  			ACCACGGTCACCGTCTCCTCA
  51E5	V H74	559	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG
  			TTGAAGCCTTCGGAGACCCTTTCCCTCACCTGCG
  			CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG
  			GAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCT
  			GGAGTGGATTGGGGAACTCGATCATAGTGGAAG
  			TATCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCAGTAGACACGTCCAAGAACCAGTT
  			CTCCCTGAAGCTGACCTCTGTGACCGCCGCGGA
  			CACGGCTGTGTATTACTGTGCGAGAGTCCTGGG
  			ATCTACTCTTGACTATTGGGGCCAGGGAACCCT
  			GGTCACCGTCTCCTCA
  51G2	V H50	560	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG
  			GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAGTTATAGCA
  			TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCATCCATTAGTAGTAGTAGTA
  			CTTACATATACTACGCAGACTCAGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAACGCCAAGAACT
  			CACTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGATA
  			CTTATATCAGTGGCTGGAACTACGGTATGGACG
  			TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  52A8	V H40	561	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCGGCTACTATT
  			TGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTAACAGTG
  			CTGCCACAAACTATGCACCGAAGTTTCAGGGCA
  			GGGTCACCGTGACCAGGGACACGTCCATCAGCA
  			CAGCCTACATGGAACTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTGCGAGAGAGG
  			GTGGAACTTACAACTGGTTCGACCCCTGGGGCC
  			AGGGAACCCTGGTCACCGTCTCCTCA
  52B8	VH77	562	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			ATGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGTTATTATTACT
  			GGAGTTGGATCCGGCAGTCCCCAGGGAAGGGAC
  			TGGAGTGGATTGGGTATATCTATTATAGTGGGA
  			GCACCAACTACAACCCCTCCCTCAAGAGTCGAG
  			TCACCATGTCAGTAGACACGTCCAAGAACCAGT
  			TCTCCCTGAAGCTGAGCTCTGTGACCGCTGCGG
  			ACACGGCCGTGTATTACTGTGCGTCTGGAACTA
  			GGGCTTTTGATATCTGGGGCCAAGGGACAATGG
  			TCACCGTCTCTTCA
  52C1	V H64	563	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGC
  			CTGGAGTGGGTGGCAGTTATATGGTATGATGGA
  			AGTAATAACTATTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAGC
  			ACGCTGTTTCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTATATATTACTGTGCGAGAGAT
  			CGGGCGGGAGCCTCTCCCGGAATGGACGTCTGG
  			GGCCAAGGGACCACGGTCACCGTCTCCTCA
  52F8	VH41	564	CAGGTGCAACTGGTGCAGTCTGGGGCGGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATTCACCTTCATCGGCTACTATA
  			CACACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTAGCAGTG
  			GTGACACAAAGTATGCACAGAAGTTTCAGGGCA
  			GGGTCACCTTGGCCAGGGACACGTCCATCAGCA
  			CAGCCTACATGGAGCTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTGCGAACAGTG
  			GCTGGTACCCGTCCTACTACTACGGTATGGACGT
  			CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA
  52H2	VH79	565	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGTACTTACTACT
  			GGAGCTGGATCCGGCAGCCCCCAGGGACGGGAC
  			TGGAATGGATTGGGTATATCTTTTACAATGGGA
  			ACGCCAACTACAGCCCCTCCCTGAAGAGTCGAG
  			TCACCTTTTCAGTGGACACGTCCAAGAACCAGTT
  			CTCCCTGAAACTGAGTTCTGTGACCGCTGCGGA
  			CACGGCCGTGTATTTTTGTGCGAGAGAAACGGA
  			CTACGGTGACTACGCACGTCCTTTTGAATACTGG
  			GGCCAGGGAACCCTGGTCACCGTCTCCTCA
  53F6	V H60	566	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTACCTATGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAGTTATATGGTATGATGGAA
  			GTAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGGCC
  			ACTATGATAGTAGTGGTCCCAGGGACTACTGGG
  			GCCAGGGAACCCTGGTCACCGTCTCCTCA
  53H5.2	VH59	567	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAGCTATGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCCAGGGGC
  			TGGAGTGGGTGGCACTTATATCATATGATGGAA
  			GTAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAAATCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCTG
  			AGGACACGGCTGTATATTACTGTGCGAGAGAGG
  			CTAACTGGGGCTACAACTACTACGGTATGGACG
  			TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  53H5.3	VH75	568	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG
  			TTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCG
  			CTGTCTATGGTGGGTCCTTCAGTGATTACTACTG
  			GAACTGGATCCGCCAGCCCCCAGGGAAGGGGCC
  			AGAGTGGATTGGGGAAATCAATCATAGTGGAAC
  			CACCAACTACAATCCGTCCCTCAAGAGTCGAGT
  			CACCATATCAGTAGACACGTCCAAGAACCAGTT
  			CTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGA
  			CACGGCTGTATATTACTGTGTGGGGATATTACG
  			ATATTTTGACTGGTTAGAATACTACTTTGACTAC
  			TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA
  54A1	V H43	569	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  55G9			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCAGTTATGATA
  			TCAACTGGGTGCGACAGGCCACTGGACAAGGGC
  			TTGAGTGGATGGGATGGATGAACCCTCACAGTG
  			GTAACACAGGCTATGCACAGAAGTTCCAGGGCA
  			GAGTCACCATGACCAGGAACACCTCCATAAATA
  			CAGCCTACATGGAGCTGAGCAGCCTGAGATCTG
  			AGGACACGGCCGTGTATTACTGTGCGAAATATA
  			ACTGGAACTACGGCGCTTTTGATTTCTGGGGCCA
  			AGGGACAATGGTCACCGTCTCTTCA
  54H10.1	V H52	570	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG
  55D1			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  48H3			GCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA
  53C11			TGAGCTGGGTCCGCCAGGCTCCGGGGAAGGGGC
  			TGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTC
  			GTACCACATACTCCGCAGACTCCGTGAAGGGCC
  			GGTTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCCGTATATTACTGTGCGAAAGAAC
  			AGCAGTGGCTGGTTTATTTTGACTACTGGGGCCA
  			GGGAACCCTGGTCACCGTCTCCTCA
  55D3	VH68	571	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCACCAGTGGTGTTTA
  			CTACTGGAACTGGATCCGCCAGCACCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACCTCTATTACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGCCTTACCATTTCAGCAGACATGTCTAAGAAC
  			CAGTTCTCCCTAAAGCTGAGCTCTGTGACTGTCG
  			CGGACACGGCCGTGTATTACTGTGCGAGAGATG
  			GTATTACTATGGTTCGGGGAGTTACTCACTACTA
  			CGGTATGGACGTCTGGGGCCAAGGGACCACGGT
  			CACCGTCTCCTCA
  55E4	V
  H70	572	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG
  49B11			TTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCG
  50H10			CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG
  53C1			GAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCT
  52C5			GGAGTGGATTGGGGAAATCAATCATAGTGAAAA
  60G5.1			CACCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCACTAGACACGTCCAATGACCAGTT
  			CTCCCTAAGACTAACCTCAGTGACCGCCGCGGA
  			CACGGCTGTCTATTACTGTGCGAGAGTAACTGG
  			AACGGATGCTTTTGATTTCTGGGGCCAAGGGAC
  			AATGGTCACCGTCTCTTCA
  55E9	V H65	573	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTTTGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCACTTATATGGTATGATGGAG
  			ATAATAAATACTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAAACA
  			GTGGCTGGGATTACTTCTACTACTACGGTATGGA
  			CGTCTGGGGCCAAGGGACCACGGTCACCGTCTC
  			CTCA
  55G5	VH78	574	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACT
  			GGAGCTGGATCCGGCAGCCCGCCGGGAAGGGA
  			CTGGAGTGGATTGGGCGTATCTATATCAGTGGG
  			AGCACCAACTACAACCCCTCCCTCGAGAATCGA
  			GTCACCATGTCAGGAGACACGTCCAAGAACCAG
  			TTCTCCCTGAAGCTGAATTCTGTGACCGCCGCGG
  			ACACGGCCGTATATTACTGTGCGGGAAGTGGGA
  			GCTACTCCTTTGACTACTGGGGCCAGGGAACCC
  			TGGTCACCGTCTCCTCA
  50G1	VH84	575	CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGCC
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAGTTATATGGAATGATGGAA
  			GTAATAAGCTTTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGATC
  			AGTATTACGATTTTTGGAGCGGTTACCCATACTA
  			TCACTACTACGGTATGGACGTCTGGGGCCAAGG
  			GACCACGGTCACCGTCTCCTCA
  56A7	VH51	576	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG
  56E4			GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAGTTATAGCA
  			TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCATCCATTAGTAGTAGTAGTA
  			CTTACATATACTACGCAGACTCAGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAACGCCAAGAACT
  			CACTGTATCTGCAAATGAACAGCCTGAGAGCCG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGATA
  			TCTATAGCAGTGGCTGGAGCTACGGTATGGACG
  			TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  56C11	VH61	577	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGA
  			CTGGAGTGGGTGGCAGTTATATGGTATGATGGA
  			AGTTATCAATTCTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGTTGTATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGAGAT
  			CACGTTTGGAGGACTTATCGTTATATCTTTGACT
  			ACTGGGGCCAGGGAACCCTGGTCACCGTCTCCT
  			CA
  56E7	V H81	578	GAGGTGCAGCTGGTGCAGTCTGGACCAGAGGTG
  			AAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGT
  			AAGGGTTCGGGATACAGTTTAACCAGCTACTGG
  			ATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGC
  			CTGGAGTGGATGGGGATCATCTATCCTGGTGAC
  			TCTGATACCAGATACAGCCCGTCCTTCCAAGGC
  			CAGGTCACCATCTCAGCCGACACGTCCATCAGC
  			ACCGCCTACCTGCAGTGGAGCAGGTTGAAGGCC
  			TCGGACACCGCCGTATATTACTGTGCGAGGGCA
  			CAACTGGGGATCTTTGACTACTGGGGCCAGGGA
  			ACCCTGGTCACCGTCTCCTCA
  56G1	V H71	579	CAGGTGCAACTACAGCAGTGGGGCGCAGGACTG
  			TTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCG
  			CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG
  			GAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCT
  			GGAGTGGATTGGGGAAATCAATCATAGTGAAAA
  			CACCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCACTAGACACGTCCAATAAGCAGTT
  			CTCCCTAAGACTAACCTCTGTGACCGCCGCGGA
  			CACGGCTGTCTATTACTGTGCGAGAGTAACTGG
  			AACGGATGCTTTTGATTTCTGGGGCCAAGGGAC
  			AATGGTCACCGTCTCTTCA
  56G3.3	VH76	580	CAGTTGCAGTTGCAGGAATCGGGCCCAGGACTG
  55B10			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGACTCCATCAGTAGTAGTAGTT
  			ACTACTGGGGCTGGATCCGCCAGCCCCCAGGGA
  			AGGGGCTGGAGTGGATTGGGATGATCTATTATA
  			GTGGGACCACCTACTACAACCCGTCCCTCAAGA
  			GTCGAGTCACCATATCCGTAGACACGTCCAAGA
  			ATCAGTTTTCCCTGAAGCTGAGTTCTGTGACCGC
  			CGCAGACACGGCTGTGTATTATTGTGCGAGAGT
  			GGCAGCAGTTTACTGGTATTTCGATCTCTGGGGC
  			CGTGGCACCCTGGTCACTGTCTCCTCA
  57B12	VH69	581	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTGGTGGCTCCATCACCAGTGGTGTTTA
  			CTACTGGAGCTGGATCCGCCAGCTCCCAGGGAA
  			GGGCCTGGAGTGGATTGGGTACATCTATTACAG
  			TGGGAGCACCTACTACAACCCGTCCCTCAAGAG
  			TCGCCTTACCATATCAGCAGACACGTCTAAGAA
  			CCAGTTCTCCCTAAAGCTGAGCTCTGTGACTGTC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAGAT
  			GGTATTACTATGGTTCGGGGAGTTACTCACTACT
  			ACGGTATGGACGTCTGGGGCCAAGGGACCACGG
  			TCACCGTCTCCTCA
  57D9	VH82	582	CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTG
  			GTGAAGCCCTCGCAGACCCTCTCACTCACCTGTG
  			CCATCTCCGGGGACAGTGTCTCTAGCAACAGTG
  			CTACTTGGAACTGGATCAGGCAGTCCCCATCGA
  			GAGGCCTTGAGTGGCTGGGAAGGACATACTACA
  			GGTCCAAGTGGTATAATGATTATGCAGTATCTGT
  			GAAAAGTCGAATAACCATCAACCCAGACACATC
  			CAAGAACCAGTTCTCCCTGCAGCTGAACTCTGT
  			GACTCCCGAGGACACGGCTGTGTATTACTGTGT
  			GGGTATTGTAGTAGTACCAGCTGTTCTCTTTGAC
  			TACTGGGGCCAGGGAACCCTGGTCACCGTCTCC
  			TCA
  58C2	V H85	583	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCACCTTCAGTAACTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGAATGATGGA
  			AATAACAAATACTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTATATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTATTACTGTGCGAGAGAT
  			CAGAATTACGATTTTTGGAATGGTTATCCCTACT
  			ACTTCTACTACGGTATGGACGTCTGGGGCCAAG
  			GGACCACGGTCACCGTCTCCTCA
  59A10	VH47	584	CAGGTGCAGGTGGTGGAGTCTGGGGGAGGCTTG
  49H4			GTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTGACTCCTACA
  			TGAGCTGGATCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGATTTCTTCCATTAGTAGTAGTGGTAG
  			TATCGTATACTTCGCAGACTCTGTGAAGGGCCG
  			ATTCACCATCTCCAGGGACATCGCCAAGAACTC
  			ACTGTATCTGCACATGAACAGCCTGAGAGCCGA
  			GGACACGGCCGTGTATTACTGTGCGAGAGAGAC
  			GTTTAGCAGTGGCTGGTTCGATGCTTTTGATATC
  			TGGGGCCAAGGGACAATGGTCACCGTCTCTTCA
  59C9	VH49	585	GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTG
  58A5			GTCAAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  57A4			GCAGCCTCTGGATTCACCTTCAGTAGCTATAGCA
  57F9			TGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCATCCATTAGTAGTAGTAGTA
  			CTTACATATACTACGCAGACTCACTGAAGGGCC
  			GATTCACCATCTCCAGAGACAACGCCAAGAACT
  			CACTGTTTCTGCAAGTGAACAGCCTGAGAGCCG
  			AAGACTCGGCTGTGTATTACTGTGCGAGAGATC
  			GATGGAGCAGTGGCTGGAACGAAGGTTTTGACT
  			ATTGGGGCCAGGGAACCCTGGTCACCGTCTCCT
  			CA
  59G10.2	VH57	586	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAACTATGGCA
  			TGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGC
  			TGGAGTGGGTGGCAATTACATCATATGGAGGAA
  			GTAATAAAAATTATGCAGACTCCGTGAAGGGCC
  			GATTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTGCAAATGAACAGCCTGAGAGCTG
  			AGGACACGGCTGTGTATTATTGTGCGAGAGAGG
  			CCGGGTATAGCTTTGACTACTGGGGCCAGGGAA
  			CCCTGGTCACCGTCTCCTCA
  59G10.3	V H53	587	GAGGTGCAACTGTTGGGATCTGGGGGAGGCTTG
  			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTTAACCACTATGCCA
  			TGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTG
  			CTGGCACATTCTACGCGGACTCCATGAAGGGCC
  			GGTTCACCATCTCCAGAGACAATTCCGAGAACA
  			CGCTGCATCTGCAGATGAACAGCCTGAGAGCCG
  			AGGACACGGCCATATATTACTGTGCGAAAGATC
  			TTAGAATAGCAGTGGCTGGTTCATTTGACTACTG
  			GGGCCAGGGAACCCTGGTCACCGTCTCCTCA
  60D7	V H66	588	CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTG
  			GTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
  			GCAGCGTCTGGATTCAACTTCAGTAGCTATGGC
  			ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
  			CTGGAGTGGGTGGCAGTTATATGGTATGATGGA
  			AGTAATAAATACTATGCAGACTCCGTGAAGGGC
  			CGATTCACCATCTCCAGAGACAATTCCAAGAAC
  			ACGCTGTATCTGCAAATGAACAGCCTGAGAGCC
  			GAGGACACGGCTGTGTTTTACTGTGCGAGAGAT
  			CAGTATTTCGATTTTTGGAGTGGTTATCCTTTCTT
  			CTACTACTACGGTATGGACGTCTGGGGCCAAGG
  			GACCACGGTCACCGTCTCCTCA
  60F9	VH55	589	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG
  48B4			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  52D6			GCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA
  			TGAGTTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCAGTTATTAGTGACAGTGGTG
  			GTAGCACATACTACGCAGACTCCGTGAAGGGCC
  			GGTTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTACAAATGAACAGCCTGAGAGCCG
  			AGGATACGGCCGTATATTACTGTGCGAAAGATC
  			ATAGCAGTGGCTGGTACTACTACGGTATGGACG
  			TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  60G5.2	VH45	590	CAGGTTCAGCTGGTGCAGTCTGGAGCTGAGGTG
  			AAGACGCCCGGGGCCTCAGTGAGGGTCTCCTGC
  			AAGGCTTCTGGTTACACCTTTACCAACTATGGTA
  			TCAGCTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAGCGCTTACAATG
  			GTTACTCAAACTATGCACAGAAGTTCCAGGACA
  			GAGTCACCATGACCACAGACACATCCACGAGCA
  			CAGCCTACATGGAGCTGAGGAGCCTGAGATCTG
  			ACGACACGGCCGTGTATTACTGTGCGAGAGAGG
  			AGAAGCAGCTCGTCAAAGACTATTACTACTACG
  			GTATGGACGTCTGGGGCCAGGGGTCCACGGTCA
  			CCGTCTCCTCA
  61G5	V H56	591	GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTG
  			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTTAGCAGCTATGCCA
  			TGAGCTGGGTCCGCCAGTCTCCAGGGAAGGGGC
  			TGGAGTGGGTCTCAGTTATTAGTGGTAGTGGTG
  			GTGACACATACTACGCAGACTCCGTGAAGGGCC
  			GGTTCACCATCTCCAGAGACAATTCCAAGAACA
  			CGCTGTATCTACAAATGAACAGCCTGAGAGCCG
  			AGGATACGGCCGTATATTACTGTGCGAAAGATC
  			ATACCAGTGGCTGGTACTACTACGGTATGGACG
  			TCTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  56G3.2	V H80	592	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGATGGCTCCATCAGTAGTTACTACT
  			GGAACTGGATCCGGCAGCCCGCCGGGAAGGGA
  			CTGGAGTGGATTGGGCGTATCTATACCAGTGGG
  			AGCACCAACTACAATCCCTCCCTCAAGAGTCGA
  			GTCACCATGTCAGTAGACACGTCCAAGAACCAG
  			TTCTCCCTGAACCTGACCTCTGTGACCGCCGCGG
  			ACACGGCCGTGTATTACTGTGCGAGAGGCCCTC
  			TTTGGTTTGACTACTGGGGCCAGGGAACCCTGG
  			TCACCGTCTCCTCA
  48G4	VH83	593	CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTG
  53C3.1			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGTTTCCGGATACACCCTCACTGAATTATCCA
  			TACACTGGGTGCGACAGGCTCCTGGAAAAGGGC
  			TTGAGTGGATGGGAGGTTTTGATCCTGAAGATG
  			GTGAAACAATCTACGCACAGAAGTTCCAGGGCA
  			GAGTCACCATGACCGAGGACACATCTACAGACA
  			CAGCCTACATGGAGCTGAGCAGCCTGAGATCTG
  			AGGACACGGCCGTGTATTACTGTGCAACACATT
  			CTGGTTCGGGGAGGTTTTACTACTACTACTACGG
  			TATGGACGTCTGGGGCCAAGGGACCACGGTCAC
  			CGTCTCCTCA
  61H5	VH86	594	CAGCTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  52B9			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGCAGTAGTAGTT
  			ACTACTGGGGCTGGATCCGCCAGCCCCCAGGGA
  			AGGGGCTGGAGTGGATTGGGAGTATCTATTATA
  			GTGGGACCACCTACTACAACCCGTCCCTCAAGA
  			GTCGAGTCACCATATCCGTAGACACGTCCAAGA
  			ACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGC
  			CGCAGACACGGCTGTGTATTACTGTGCGAGAGT
  			GGCAGCAGTTTACTGGTACTTCGATCTCTGGGGC
  			CGTGGCACCCTGGTCACTGTCTCCTCA
  50D4	VH87	595	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  			AAGAAGACTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACCAGTCATGAT
  			ATCAACTGGGTGCGACAGGCCACTGGACACGGG
  			CTTGAGTGGATGGGATGGATGAACCCTTACAGT
  			GGTAGCACAGGCCTCGCACAGAGGTTCCAGGAC
  			AGAGTCACCATGACCAGGAACACCTCCATAAGC
  			ACAGCCTACATGGAGCTGAGCAGCCTGAGATCT
  			GAGGACACGGCCGTGTATTACTGTGCGAGAGAC
  			CTTAGCAGTGGCTACTACTACTACGGTTTGGACG
  			TGTGGGGCCAAGGGACCACGGTCACCGTCTCCT
  			CA
  50G5v1	VH88	596	CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTG
  50G5v2			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCCTCTGGATACCCCTTCATCGGCTACTATA
  			TGCACTGGGTGCGACAGGCCCCTGGACAAGGGC
  			TTGAGTGGATGGGATGGATCAACCCTGACAGTG
  			GTGGCACAAACTATGCACAGAAGTTTCAGGGCA
  			GGGTCACCATGACCAGGGACACGTCCATCACCA
  			CAGCCTACATGGAGCTGAGCAGGCTGAGATCTG
  			ACGACACGGCCGTTTTTTACTGTGCGAGAGGCG
  			GATACAGCTATGGTTACGAGGACTACTACGGTA
  			TGGACGTCTGGGGCCAAGGGACCACGGTCACCG
  			TCTCCTCA
  51C1	VH89	597	CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTG
  			TTGAAGCCTTCGGAGACCCTGTCCCTCACTTGCG
  			CTGTCTATGGTGGGTCCTTCAGTGGTTACTACTG
  			GAGCTGGATCCGCCAGCCCCCAGGGAAGGGTCT
  			GGAGTGGATTGGGGAAATCAATCATAGTGAAAA
  			CACCAACTACAACCCGTCCCTCAAGAGTCGAGT
  			CACCATATCACTAGACACGTCCCATGACCAGTT
  			CTCCCTAAGACTAACCTCTGTGACCGCCGCGGA
  			CACGGCTGTCTATTACTGTGCGAGAGTAACTGG
  			AACGGATGCTTTTGATTTCTGGGGCCAAGGGAC
  			AATGGTCACCGTCTCTTCA
  53C3.2	V H90	598	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCACAGACCCTGTCCCTCACCTGCA
  			CTGTCTCTAATGGCTCCATCAATAGTGGTAATTA
  			CTACTGGAGCTGGATCCGCCAGCACCCAGGAAA
  			GGGCCTGGAGTGGATTGGGTACATCTATCACAG
  			TGGGAGCGCCTACTACAACCCGTCCCTCAAGAG
  			TCGAGTTACCATATCAGTGGACACGTCTAAGAA
  			CCAGTTCTCCCTAAAGCTGAGTTCTGTGACTGCC
  			GCGGACACGGCCGTGTATTACTGTGCGAGAACT
  			ACGGGTGCTTCTGATATCTGGGGCCAAGGGATA
  			ATGGTCACCGTCTCTTCA
  54H10.3	VH91	599	CAGGTGCAGGTAGTGCAGTCTGGGACTGAGGTG
  			AAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGC
  			AAGGCTTCTGGATACACCTTCACAGGCTACTAT
  			ATACATTGGGTGCGACAGGCCCCTGGACAAGGG
  			CTTGAGTGGATGGGATGGATCAACCCTAACAGT
  			GGTGGCACAAACTATGCACAGAAGTTTCGGGGC
  			AGGGTCACCATGACCAGGGACACGTCCATCAGC
  			ACAGCCTACATGGAGCTGAGCAGGCTGAGATCT
  			GACGACACGGCCGTGTATTACTGTGCGAGAGAG
  			GAAGACTACAGTGACCACCACTACTTTGACTAC
  			TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA
  55A7	VH92	600	CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTG
  			GTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
  			ACTGTCTCTGGTGGCTCCATCAGTAGTTACTACT
  			GGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
  			CTGGAGTGGATTGGGTATATCTATTACAGTGGG
  			AGCACCAACTACAACCCCTCCCTCAAGAGTCGA
  			GTCACCATATCAGTAGACACGTCCAAGAACCAG
  			TTCTCCCTGAGGCTGAGCTCTGTGACCGCTGCGG
  			ACACGGCCGTGTATTACTGTGCGAGAGGGATAA
  			CTGGAACTATTGACTTCTGGGGCCAGGGAACCC
  			TGGTCACCGTCTCCTCA
  55E6	VH93	601	GAAGTGCAGTTGGTGGAGTCTGGGGGAGGCTTG
  			GTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
  			GCAGCCTCTGGATTCACCTTCAGTAGCTATAGCA
  			TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGC
  			TGGAGTGGATTTCATACATTAGTAGTGGTAGTA
  			GTACCATATACCACGCAGACTCTGTGAAGGGCC
  			GATTCACCATTTCCAGAGACAATGCCAAGAACT
  			CACTGTATCTGCAAATGAACAGCCTGAGAGACG
  			AGGACACGGCTGTGTATTACTGTGCGAGAGAAG
  			GGTACTATGATAGTAGTGGTTATTACTACAACG
  			GTATGGACGTCTGGGGCCAAGGGACCACGGTCA
  			CCGTCTCCTCA
  61E1	VH94	602	CAGGTACAGCTACAGCAGTCAGGTCCAGGACTG
  			GTGAAGCCCTCGCAGACCCTCTCACTCACCTGTG
  			CCATCTCCGGGGACAGTGTCTCTAGCAACAGTG
  			CTGCTTGGAACTGGATCAGGCAGTCCCCATCGA
  			GAGGCCTTGAGTGGCTGGGAAGGACATACTACA
  			GGTCCAAGTGGTATAATGATTATGCAGTATCTGT
  			GAAAAGTCGAATAACCATCACCCCAGACACATC
  			CAAGAACCAGTTCTCCCTGCAGCTGAAGTCTGT
  			GACTCCCGAGGACACGGCTATTTATTACTGTGC
  			AAGAGAGGGCAGCTGGTCCTCCTTCTTTGACTA
  			CTGGGGCCAGGGAACCCTGGTCACCGTTTCCTCA

• Each of the heavy chain variable regions listed in Table 2B can be combined with any of the light chain variable regions shown in Table 2A to form an antigen binding protein. Examples of such combinations include V _H1 combined with any of V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100; V _H2 combined with any of V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100; V _H3 combined with any of V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100; and so on.
• In some instances, the antigen binding protein includes at least one heavy chain variable region and/or one light chain variable region from those listed in Tables 2A and 2B. In some instances, the antigen binding protein includes at least two different heavy chain variable regions and/or light chain variable regions from those listed in Table 2B. An example of such an antigen binding protein comprises (a) one V _H1, and (b) one of V _H2, V _H3, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94. Another example comprises (a) one V _H2, and (b) one of V _H1, V _H3, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94. Yet another example comprises (a) one V _H3, and (b) one of V _H1, V _H2, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94, etc. Still another example of such an antigen binding protein comprises (a) one V _L1, and (b) one of V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100. Again another example of such an antigen binding protein comprises (a) one V _L2, and (b) one of V _L1, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100. Again another example of such an antigen binding protein comprises (a) one V _L3, and (b) one of V _L1, V _L2, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100, etc.
• The various combinations of heavy chain variable regions can be combined with any of the various combinations of light chain variable regions.
• In other embodiments, an antigen binding protein comprises two identical light chain variable regions and/or two identical heavy chain variable regions. As an example, the antigen binding protein can be an antibody or immunologically functional fragment thereof that includes two light chain variable regions and two heavy chain variable regions in combinations of pairs of light chain variable regions and pairs of heavy chain variable regions as listed in Tables 2A and 2B.
• Some antigen binding proteins that are provided comprise a heavy chain variable domain comprising a sequence of amino acids that differs from the sequence of a heavy chain variable domain selected from V _H1, V _H2, V _H3, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94 at only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid residues, wherein each such sequence difference is independently either a deletion, insertion or substitution of one amino acid, with the deletions, insertions and/or substitutions resulting in no more than 15 amino acid changes relative to the foregoing variable domain sequences. The heavy chain variable region in some antigen binding proteins comprises a sequence of amino acids that has at least 70%, 75%, 80%, 85%, 90%, 95%, 97% or 99% sequence identity to the amino acid sequences of the heavy chain variable region of V _H1, V _H2, V _H3, V _H4, V _H5, V _H6, V _H7, V _H8, V _H9, V _H10, V _H11, V _H12, V _H13, V _H14, V _H15, V _H16, V _H17, V_H18, V_H19, V _H20, V_H21 V_H22, V _H23, V _H24, V _H25, V _H26, V _H27, V_H28, V_H29, V _H30, V _H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V _H38, V_H39, V _H40, V_H41, V_H42, V _H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V _H50, V_H51, V _H52, V _H53, V_H54, V_H55, V _H56, V_H57, V_H58, V_H59, V _H60, V_H61, V_H62, V_H63, V _H64, V _H65, V _H66, V_H67, V_H68, V_H69, V _H70, V _H71, V _H72, V _H73, V _H74, V_H75, V_H76, V_H77, V_H78, V_H79, V _H80, 81, V_H82, V_H83, V_H84, V _H85, V_H 86, V_H 87, V_H88, V_H89, V _H90, V_H91, V_H92, V_H93, and V_H94.
• Certain antigen binding proteins comprise a light chain variable domain comprising a sequence of amino acids that differs from the sequence of a light chain variable domain selected from V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, VAL V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100 at only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acid residues, wherein each such sequence difference is independently either a deletion, insertion or substitution of one amino acid, with the deletions, insertions and/or substitutions resulting in no more than 15 amino acid changes relative to the foregoing variable domain sequences. The light chain variable region in some antigen binding proteins comprises a sequence of amino acids that has at least 70%, 75%, 80%, 85%, 90%, 95%, 97% or 99% sequence identity to the amino acid sequences of the light chain variable region of V _L1, V _L2, V _L3, V _L4, V _L5, V _L6, V _L7, V _L8, V _L9, V _L10, V _L11, V _L12, V _L13, V _L14, V _L15, V _L16, V _L17, V_L18, V_L19, V _L20, V_L21, V_L22, V _L23, V _L24, V _L25, V _L26, V _L27, V_L28, V_L29, V _L30, V _L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V _L38, V_L39, V _L40, V_L41, V_L42, V _L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V _L50, V_L51, V _L52, V _L53, V_L54, V_L55, V _L56, V_L57, V_L58, V_L59, V _L60, V_L61, V_L62, V_L63, V _L64, V _L65, V _L66, V_L67, V_L68, V_L69, V _L70, V _L71, V _L72, V _L73, V _L74, V_L75, V_L76, V_L77, V_L78, V_L79, V _L80, V _L81, V_L82, V_L83, V_L84, V _L85, V_L86, V_L87, V_L88, V_L89, V _L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V _L100.
• In additional instances, antigen binding proteins comprise the following pairings of light chain and heavy chain variable domains: V _L1 with V _H1, V _L2 with V _H1, V _L3 with V _H2 or V _H3, V _L4 with V _H4, V _L5 with V _H5, V _L6 with V _H6, V _L7 with V _H6, V _L8 with V _H7 or V _H8, V _L9 with V _H9, V _L10 with V _H9, V _L11 with V _H 10, V _L12 with V _H11, V _L13 with V _H12, V _L13 with V _H14, V _L14 with V _H13, V _L15 with V _H14, V _L16 with V _H15, V _L17 with V _H16, V_L18 with V _H17, V_L19 with V_H18, V _L20 with V_H19, V_L21 with V _H20, V_L22 with V_H21, V _L23 with V_H22, V _L24 with V _H23, V _L25 with V _H24, V _L26 with V _H25, V _L27 with V _H26, V_L28 with V _H27, V_L29 with V_H28, V _L30 with V_H29, V _L31 with V _H30, V_L32 with V _H31, V_L33 with V_H32, V_L34 with V_H33, V_L35 with V_H34, V_L36 with V_H35, V_L37 with V_H36, V _L38 with V_H37, V_L39 with V _H38, V _L40 with V_H39, V_L41 with V _H40, V_L42 with V_H41, V _L43 with V_H42, V_L44 with V _H43, V_L45 with V_H44, V_L46 with V_H45, V_L47 with V_H46, V_L48 with V_H47, V_L49 with V_H48, V _L50 with V_H49, V_L51 with V _H50, 52 with V_H51, V _L53 with V _H52, V_L54 with V _H53, V_L55 with 54, and V _L56 with V_H54, V_L57 with V_H54, V_L58 with V_H55, V_L59 with V _H56, V _L60 with V_H57, V_L61 with V_H58, V_L62 with V_H59, V_L63 with V _H60, V _L64 with V _H1, V _L65 with V_H62, V _L66 with V_H63, V_L67 with V _H64, V_L68 with V _H65, V_L69 with V _H66, V _L70 with V_H67, V _L71 with V_H68, V _L72 with V_H69, V _L73 with V _H70, V _L74 with V _H70, and V_L75 with V _H70, V_L76 with V _H71, V_L77 with V _H72, V_L78 with V _H73, V_L79 with V _H74, V _L80 with V_H75, V _L81 with V_H76, V_L82 with V_H77, V_L83 with V_H78, V_L84 with V_H79, V _L85 with V _H80, V_L86 with V _H81, V_L87 with V_H82, V_L88 with V_H86, V_L89 with V_H83, V _L90 with V_H84, V_L91 with V _H85, V_L 92 with V_H 87, V_L 93 with V_H 88, V_L 94 with V_H 88, V_L 95 with V_H 89, V_L 96 with V _H 90, V_L 97 with V_H 91, V_L 98 with V_H 92, V_L 99 with V_H 93, and V _L 100 with V_H 94.
• In some instances, the antigen binding proteins in the above pairings can comprise amino acid sequences that have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the specified variable domains.
• Still other antigen binding proteins, e.g., antibodies or immunologically functional fragments, include variant forms of a variant heavy chain and a variant light chain as just described.
Antigen Binding Protein CDRs
• In various embodiments, the antigen binding proteins disclosed herein can comprise polypeptides into which one or more CDRs are grafted, inserted and/or joined. An antigen binding protein can have 1, 2, 3, 4, 5 or 6 CDRs. An antigen binding protein thus can have, for example, one heavy chain CDR1 (“CDRH1”), and/or one heavy chain CDR2 (“CDRH2”), and/or one heavy chain CDR3 (“CDRH3”), and/or one light chain CDR1 (“CDRL1”), and/or one light chain CDR2 (“CDRL2”), and/or one light chain CDR3 (“CDRL3”). Some antigen binding proteins include both a CDRH3 and a CDRL3. Specific heavy and light chain CDRs are identified in Tables 3A and 3B, respectively, infra.
• Complementarity determining regions (CDRs) and framework regions (FR) of a given antibody can be identified using the system described by Kabat et al., (1991) “Sequences of Proteins of Immunological Interest”, 5th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242. Although presented in the Kabat nomenclature scheme, as desired, the CDRs disclosed herein can also be redefined according an alternative nomenclature scheme, such as that of Chothia (see Chothia & Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342:878-883 or Honegger & Pluckthun, (2001) J. Mol. Biol. 309:657-670). Certain antibodies that are disclosed herein comprise one or more amino acid sequences that are identical or have substantial sequence identity to the amino acid sequences of one or more of the CDRs presented in Table 3A (CDRHs) and Table 3B (CDRLs), infra.

• TABLE 3A
  Exemplary CDRH Sequences

  		Con-
  		tained
  	SEQ	in
  	ID	Refer-	Designa-
  Clone	NO:	ence	tion	Sequence

  48C9	603	V H73	CDRH1-1	GYYWT
  49A12		V H73
  51E2		V H73
  48F3	604	V H72	CDRH1-2	GYYWS
  51E5		V H74
  52C5		V H70
  55E4		V H70
  60G5.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  56G1		V H71
  51C1		VH89
  48F8	605	VH48	CDRH1-3	SYSMN
  51G2		V H50
  56A7		VH51
  53B9		VH48
  56B4		VH48
  57E7		VH48
  57F11		VH48
  56E4		VH51
  55E6		VH93
  48H11	606	VH39	CDRH1-4	GYYKH
  48G4	607	VH83	CDRH1-5	ELSIH
  53C3.1		VH83
  49A10	608	VH62	CDRH1-6	NYGMH
  58C2		V H85
  59G10.2		VH57
  48D4		VH62
  49C8	609	VH44	CDRH1-7	SYDID
  52H1		VH44
  49G2	610	VH63	CDRH1-8	NYGMR
  50C12		VH63
  55G11		VH63
  49G3	611	VH46	CDRH1-9	NPRMGVS
  49H12	612	VH42	CDRH1-10	SYDIN
  54A1		V H43
  55G9		V H43
  50G1	613	VH84	CDRH1-11	SYGLH
  51A8	614	VH58	CDRH1-12	SYGMH
  52C1		V H64
  53H5.2		VH59
  56C11		VH61
  60D7		V H66
  64H5		V H7
  65G4		V H8
  66G2		V H11
  68G5		V H12
  64C8		V H23
  67G8		V H27
  68D3v2
  51C10.1	615	VH54	CDRH1-13	NYAMS
  59D10v1		VH54
  59D10v2		VH54
  51C10.2	616	VH67	CDRH1-14	SGGYYWS
  64A6		VH29
  52A8	617	V H40	CDRH1-15	GYYLH
  66B4		V H10
  52B8	618	VH77	CDRH1-16	YYYWS
  52F8	619	VH41	CDRH1-17	GYYTH
  52H2	620	VH79	CDRH1-18	TYYWS
  53F6	621	V H60	CDRH1-19	TYGMH
  53H5.3	622	VH75	CDRH1-20	DYYWN
  54H10.1	623	V H52	CDRH1-21	SYAMS
  60F9		VH55
  61G5		V H56
  55D1		V H52
  48H3		V H52
  53C11		V H52
  48B4		VH55
  52D6		VH55
  55D3	624	VH68	CDRH1-22	SGVYYWN
  55E9	625	V H65	CDRH1-23	SFGMH
  55G5	626	VH78	CDRH1-24	SYYWS
  65C3		V H5
  68D5		V H5
  67F5		V H31
  55A7		VH92
  56E7	627	V H81	CDRH1-25	SYWIG
  67A5		VH34
  67C10		VH35
  64H6		VH36
  56G3.2	628	V H80	CDRH1-26	SYYWN
  56G3.3	629	VH76	CDRH1-27	SSSYYWG
  55B10		VH76
  61H5		VH86
  52B9		VH86
  57B12	630	VH69	CDRH1-28	SGVYYWS
  57D9	631	VH82	CDRH1-29	SNSATWN
  59A10	632	VH47	CDRH1-30	DSYMS
  49H4		VH47
  59C9	633	VH49	CDRH1-31	SYSMS
  58A5		VH49
  57A4		VH49
  57F9		VH49
  59G10.3	634	V H53	CDRH1-32	HYAMS
  60G5.2	635	VH45	CDRH1-33	NYGIS
  63G8	636	V H1	CDRH1-34	SYGIH
  64A8		V H1
  67B4		V H1
  68D3		V H1
  64E6	637	V H2	CDRH1-35	SGDYYWT
  65E8		V H2
  65F11		V H2
  67G7		V H2
  63H11		V H3
  63F5		V H13
  65C1		V H15
  66F6		V H14
  63B6	638	V H4	CDRH1-36	SGDYYWS
  64D4		V H4
  65F9		V H30
  64B10		VH32
  64B10v2
  63E6	639	V H6	CDRH1-37	GYYMH
  66F7		V H6
  50G5 v1		VH88
  50G5 v2		VH88
  67G10v1	640	V H9	CDRH1-38	NAWMS
  67G10v2		VH9VH21
  63A10		VH22
  65H11
  53C3.2	641	V H90	CDRH1-39	SGNYYWS
  64A7	642	V H16	CDRH1-40	SDTSYWG
  50D4	643	VH87	CDRH1-41	SHDIN
  61E1	644	VH94	CDRH1-42	SNSAAWN
  66D4	645	V H17	CDRH1-43	GYYIH
  54H10.3		VH91
  65B1	646	VH18	CDRH1-44	GYFMH
  67A4	647	VH19	CDRH1-45	TYDMH
  65B4	648	V H20	CDRH1-46	SYDMH
  65E3	649	V H24	CDRH1-47	NYNMH
  65D4	650	V H25	CDRH1-48	FYGMH
  65D1	651	V H26	CDRH1-49	YYYIH
  65B7	652	VH28	CDRH1-50	SDAYYWS
  68C8	653	VH33	CDRH1-51	SGDNYWS
  63F9	654	VH37	CDRH1-52	SGGYYWN
  67F6v1	655	V H38	CDRH1-53	GYWIG
  67F6v2		V H38
  48C9	656	V H73	CDRH2-1	EINHSENTNYNPSLKS
  52C5		V H70
  55E4		V H70
  56G1		V H71
  49A12		V H73
  51E2		V H73
  60G5.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  51C1		VH89
  48F3	657	V H72	CDRH2-2	EITHTGSSNYNPSLKS
  48F8	658	VH48	CDRH2-3	SISSSSSYEYYVDSVKG
  53B9		VH48
  56B4		VH48
  57E7		VH48
  57F11		VH48
  48H11	659	VH39	CDRH2-4	WINPNSGATKYAQKFQG
  48G4	660	VH83	CDRH2-5	GFDPEDGETIYAQKFQG
  53C3.1		VH83
  49A10	661	VH62	CDRH2-6	IIWYDGSNKNYADSVKG
  48D4		VH62
  49C8	662	VH44	CDRH2-7	WMNPNGGNTGYAQKFQG
  52H1		VH44
  49G2	663	VH63	CDRH2-8	LIWYDGSNKFYADSVKG
  50C12		VH63
  55G11		VH63
  49G3	664	VH46	CDRH2-9	HIFSNDEKSYSTSLKS
  49H12	665	VH42	CDRH2-10	WMNPYSGSTGYAQNFQG
  50G1	666	VH84	CDRH2-11	VIWNDGSNKLYADSVKG
  51A8	667	VH58	CDRH2-12	VISYDGSNKYYADSVKG
  63G8		V H1
  64A8		V H1
  67B4		V H1
  68D3		V H1
  51C10.1	668	VH54	CDRH2-13	GISGSSAGTYYADSVKG
  59D10v1		VH54
  59D10v2		VH54
  51C10.2	669	VH67	CDRH2-14	YIYYNGSPYDNPSLKR
  51E5	670	V H74	CDRH2-15	ELDHSGSINYNPSLKS
  51G2	671	V H50	CDRH2-16	SISSSSTYIYYADSVKG
  56A7		VH51
  56E4		VH51
  52A8	672	V H40	CDRH2-17	WINPNSAATNYAPKFQG
  52B8	673	VH77	CDRH2-18	YIYYSGSTNYNPSLKS
  55A7		VH92
  52C1	674	V H64	CDRH2-19	VIWYDGSNNYYADSVKG
  52F8	675	VH41	CDRH2-20	WINPSSGDTKYAQKFQG
  52H2	676	VH79	CDRH2-21	YIFYNGNANYSPSLKS
  53F6	677	V H60	CDRH2-22	VIWYDGSNKYYADSVKG
  60D7		V H66
  65D4		V H25
  53H5.2	678	VH59	CDRH2-23	LISYDGSNKYYADSVKG
  53H5.3	679	VH75	CDRH2-24	EINHSGTTNYNPSLKS
  54A1	680	V H43	CDRH2-25	WMNPHSGNTGYAQKFQG
  55G9		V H43
  54H10.1	681	V H52	CDRH2-26	AISGSGRTTYSADSVKG
  55D1		V H52
  48H3		V H52
  53C11		V H52
  55D3	682	VH68	CDRH2-27	YLYYSGSTYYNPSLKS
  55E9	683	V H65	CDRH2-28	LIWYDGDNKYYADSVKG
  55G5	684	VH78	CDRH2-29	RIYISGSTNYNPSLEN
  56C11	685	VH61	CDRH2-30	VIWYDGSYQFYADSVKG
  56E7	686	V H81	CDRH2-31	IIYPGDSDTRYSPSFQG
  67A5		VH34
  67C10		VH35
  67F6v1		V H38
  67F6v2		V H38
  56G3.2	687	V H80	CDRH2-32	RIYTSGSTNYNPSLKS
  56G3.3	688	VH76	CDRH2-33	MIYYSGTTYYNPSLKS
  55B10		VH76
  56G3.3		VH76
  57B12	689	VH69	CDRH2-34	YIYYSGSTYYNPSLKS
  63H11		V H3
  66F6		V H14
  65F9		V H30
  57D9	690	VH82	CDRH2-35	RTYYRSKWYNDYAVSVKS
  61E1		VH94
  58C2	691	V H85	CDRH2-36	VIWNDGNNKYYADSVKG
  59A10	692	VH47	CDRH2-37	SISSSGSIVYFADSVKG
  49H4		VH47
  59C9	693	VH49	CDRH2-38	SISSSSTYIYYADSLKG
  58A5		VH49
  57A4		VH49
  57F9		VH49
  59G10.2	694	VH57	CDRH2-39	ITSYGGSNKNYADSVKG
  59G10.3	695	V H53	CDRH2-40	AISGSGAGTFYADSMKG
  60F9	696	VH55	CDRH2-41	VISDSGGSTYYADSVKG
  48B4		VH55
  52D6		VH55
  60G5.2	697	VH45	CDRH2-42	WISAYNGYSNYAQKFQD
  61G5	698	V H56	CDRH2-43	VISGSGGDTYYADSVKG
  64E6	699	V H2	CDRH2-44	YIYYTGSTYYNPSLKS
  65E8		V H2
  65F11		V H2
  67G7		V H2
  63B6	700	V H4	CDRH2-45	YIYYSGTTYYNPSLKS
  64D4		V H4
  65C3	701	V H5	CDRH2-46	YIYYTGSTNYNPSLKS
  68D5		V H5
  63E6	702	V H6	CDRH2-47	WMNPNSGATKYAQKFQG
  66F7		V H6
  64H5	703	V H7	CDRH2-48	VIWDDGSNKYYADSVKG
  65G4		V H8
  67G10v1	704	V H9	CDRH2-49	RIKSKTDGGTTEYAAPVKG
  67G10v2		V H9
  63F5	705	V H13	CDRH2-50	YIYYSGSAYYNPSLKS
  64A7	706	V H16	CDRH2-51	NIYYSGTTYFNPSLKS
  65C1	707	V H15	CDRH2-52	YIFYSGSTYYNPSLKS
  65B7		VH28
  66B4	708	V H10	CDRH2-53	WINPNSGGTDYAQKFQG
  66G2	709	V H11	CDRH2-54	GISYDGSNKNYADSVKG
  68G5	710	V H12	CDRH2-55	VIWYDGSNKYHADSVKG
  66D4	711	V H17	CDRH2-56	WINPPSGATNYAQKFRG
  65B1	712	VH18	CDRH2-57	WINPNSGATNYAQKFHG
  67A4	713	VH19	CDRH2-58	AIGIAGDTYYSDSVKG
  65B4	714	V H20	CDRH2-59	TIDTAGDAYYPGSVKG
  63A10	715	VH21	CDRH2-60	RIKSKTDGGTTDYAAPVKG
  67G10v1
  67G10v2
  65H11	716	VH22	CDRH2-61	RIIGKTDGGTTDYAAPVKG
  64C8	717	V H23	CDRH2-62	VISYDGSNKHYADSVKG
  65E3	718	V H24	CDRH2-63	VLWYDGNTKYYADSVKG
  65D1	719	V H26	CDRH2-64	LIWYDGSNKDYADSVKG
  67G8	720	V H27	CDRH2-65	VIWYDGSNKDYADSVKG
  64A6	721	VH29	CDRH2-66	YIYYSGGTHYNPSLKS
  67F5	722	V H31	CDRH2-67	YIYYSGNTNYNPSLKS
  64B10	723	VH32	CDRH2-68	FIYYSGGTNYNPSLKS
  68C8	724	VH33	CDRH2-69	FMFYSGSTNYNPSLKS
  64H6	725	VH36	CDRH2-70	IIYPGDSETRYSPSFQG
  63F9	726	VH37	CDRH2-71	YIYDSGSTYYNPSLKS
  61H5	727	VH86	CDRH2-72	SIYYSGTTYYNPSLKS
  52B9		VH86
  50G5v1	728	VH88	CDRH2-73	WINPDSGGTNYAQKFQG
  50G5v2		VH88
  54H10.3	729	VH91	CDRH2-74	WINPNSGGTNYAQKFRG
  50D4	730	VH87	CDRH2-75	WMNPYSGSTGLAQRFQD
  55E6	731	VH93	CDRH2-76	YISSGSSTIYHADSVKG
  53C3.2	732	V H90	CDRH2-77	YIYHSGSAYYNPSLKS
  64B10v2	1868	VH96	CDRH2-78	FIYYSGGTNYNPPLKS
  68D3v2	1869	VH95	CDRH2-79	FISYAGSNKYYADSVKG
  48C9	733	V H73	CDRH3-1	ESGNFPFDY
  49A12		V H73
  51E2		V H73
  48F3	734	V H72	CDRH3-2	GGILWFGEQAFDI
  48F8	735	VH48	CDRH3-3	SLSIAVAASDY
  53B9		VH48
  56B4		VH48
  57E7		VH48
  57F11		VH48
  48H11	736	VH39	CDRH3-4	EVPDGIVVAGSNAFDF
  48G4	737	VH83	CDRH3-5	HSGSGRFYYYYYGMDV
  53C3.1		VH83
  49A10	738	VH62	CDRH3-6	DQDYDFWSGYPYFYYYGMDV
  48D4		VH62
  49C8	739	VH44	CDRH3-7	GKEFSRAEFDY
  52H1		VH44
  49G2	740	VH63	CDRH3-8	DRYYDFWSGYPYFFYYGLDV
  50C12		VH63
  55G11		VH63
  49G3	741	VH46	CDRH3-9	VDTLNYHYYGMDV
  49H12	742	VH42	CDRH3-10	YNWNYGAFDF
  54A1		V H43
  55G9		V H43
  50G1	743	VH84	CDRH3-11	DQYYDFWSGYPYYHYYGMDV
  51A8	744	VH58	CDRH3-12	ADGDYPYYYYYYGMDV
  51C10.1	745	VH54	CDRH3-13	DWSIAVAGTFDY
  59D10v1		VH54
  59D10v2		VH54
  51C10.2	746	VH67	CDRH3-14	GALYGMDV
  51E5	747	V H74	CDRH3-15	VLGSTLDY
  51G2	748	V H50	CDRH3-16	DTYISGWNYGMDV
  52A8	749	V H40	CDRH3-17	EGGTYNWFDP
  52B8	750	VH77	CDRH3-18	GTRAFDI
  52C1	751	V H64	CDRH3-19	DRAGASPGMDV
  52C5	752	V H70	CDRH3-20	VTGTDAFDF
  60G5.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  51C1		VH89
  55E4		V H70
  56G1		V H71
  52F8	753	VH41	CDRH3-21	SGWYPSYYYGMDV
  52H2	754	VH79	CDRH3-22	ETDYGDYARPFEY
  53F6	755	V H60	CDRH3-23	GHYDSSGPRDY
  53H5.2	756	VH59	CDRH3-24	EANWGYNYYGMDV
  53H5.3	757	VH75	CDRH3-25	ILRYFDWLEYYFDY
  61E1	758	VH94	CDRH3-26	EGSWSSFFDY
  54H10	759	V H52	CDRH3-27	EQQWLVYFDY
  55D1		V H52
  48H3		V H52
  53C11		V H52
  55D3	760	VH68	CDRH3-28	DGITMVRGVTHYYGMDV
  57B12		VH69
  55E6	761	VH93	CDRH3-29	EGYYDSSGYYYNGMDV
  55E9	762	V H65	CDRH3-30	NSGWDYFYYYGMDV
  55G5	763	VH78	CDRH3-31	SGSYSFDY
  56A7	764	VH51	CDRH3-32	DIYSSGWSYGMDV
  56E4		VH51
  56C11	765	VH61	CDRH3-33	DHVWRTYRYIFDY
  56E7	766	V H81	CDRH3-34	AQLGIFDY
  50G5v1	767	VH88	CDRH3-35	GGYSYGYEDYYGMDV
  50G5v2		VH88
  56G3.2	768	V H80	CDRH3-36	GPLWFDY
  56G3.3	769	VH76	CDRH3-37	VAAVYWYFDL
  55B10		VH76
  61H5		VH86
  52B9		VH86
  55A7	770	VH92	CDRH3-38	GITGTIDF
  57D9	771	VH82	CDRH3-39	IVVVPAVLFDY
  58C2	772	V H85	CDRH3-40	DQNYDFWNGYPYYFYYGMDV
  59A10	773	VH47	CDRH3-41	ETFSSGWFDAFDI
  49H4		VH47
  59C9	774	VH49	CDRH3-42	DRWSSGWNEGFDY
  58A5		VH49
  57A4		VH49
  57F9		VH49
  53C3.2	775	V H90	CDRH3-43	TTGASDI
  59G10.2	776	VH57	CDRH3-44	EAGYSFDY
  59G10.3	777	V H53	CDRH3-45	DLRIAVAGSFDY
  60D7	778	V H66	CDRH3-46	DQYFDFWSGYPFFYYYGMDV
  60F9	779	VH55	CDRH3-47	DHSSGWYYYGMDV
  48B4		VH55
  52D6		VH55
  60G5.2	780	VH45	CDRH3-48	EEKQLVKDYYYYGMDV
  61G5	781	V H56	CDRH3-49	DHTSGWYYYGMDV
  63G8	782	V H1	CDRH3-50	TVTKEDYYYYGMDV
  64A8		V H1
  67B4		V H1
  68D3		V H1
  66G2		V H11
  64E6	783	V H2	CDRH3-51	MTTPYWYFDL
  65E8		V H2
  65F11		V H2
  67G7		V H2
  63H11		V H3
  63F5		V H13
  66F6		V H14
  63B6	784	V H4	CDRH3-52	MTTPYWYFGL
  64D4		V H4
  65C3	785	V H5	CDRH3-53	EYYYGSGSYYP
  68D5		V H5
  67F5		V H31
  63E6	786	V H6	CDRH3-54	ELGDYPFFDY
  66F7		V H6
  64H5	787	V H7	CDRH3-55	EYVAEAGFDY
  65G4		V H8
  67G10v1	788	V H9	CDRH3-56	DSSGSYYVEDYFDY
  67G10 v2		V	H9
  63A10		VH21
  65H11		VH22
  64A7	789	V H16	CDRH3-57	LRGVYWYFDL
  65C1	790	V H15	CDRH3-58	MTSPYWYFDL
  66B4	791	V H10	CDRH3-59	DAATGRYYFDN
  68G5	792	V H12	CDRH3-60	DPGYSYGHFDY
  66D4	793	V H17	CDRH3-61	ETGTWSFFDY
  65B1	794	VH18	CDRH3-62	ELGIFNWFDP
  67A4	795	VH19	CDRH3-63	DRSSGRFGDYYGMDV
  65B4	796	V H20	CDRH3-64	DRSSGRFGDFYGMDV
  64C8	797	V H23	CDRH3-65	ELLWFGEYGVDHGMDV
  65E3	798	V H24	CDRH3-66	DVYGDYFAY
  65D4	799	V H25	CDRH3-67	ALNWNFFDY
  65D1	800	V H26	CDRH3-68	EGTTRRGFDY
  67G8	801	V H27	CDRH3-69	SAVALYNWFDP
  65B7	802	VH28	CDRH3-70	ESRILYFNGYFQH
  64A6	803	VH29	CDRH3-71	VLHYSDSRGYSYYSDF
  65F9	804	V H30	CDRH3-72	VLHYYDSSGYSYYFDY
  64B10v1	805	VH32	CDRH3-73	YSSTWDYYYGVDV
  64B10v2		VH32
  68C8	806	VH33	CDRH3-74	YRSDWDYYYGMDV
  67A5	807	VH34	CDRH3-75	RASRGYRFGLAFAI
  67C10	808	VH35	CDRH3-76	RASRGYRYGLAFAI
  64H6	809	VH36	CDRH3-77	VAVSAFNWFDP
  63F9	810	VH37	CDRH3-78	DVLMVYTKGGYYYYGVDV
  67F6v1	811	V H38	CDRH3-79	RASRGYSYGHAFDF
  67F6v2		V	H38
  50D4	812	VH87	CDRH3-80	DLSSGYYYYGLDV
  54H10.3	813	VH91	CDRH3-81	EEDYSDHHYFDY
  66D4	1870	V H17	CDRH3-82	ETGTWNFFDY
  68D3v2	1871	VH95	CDRH3-83	TVTEEDYYYYGMDV

• TABLE 3B
  Exemplary CDRL Sequences

  	SEQ	Contained
  	ID	in	Desig-	Amino Acid
  Clone	NO:	Reference	nation	Sequence

  48C9	814	VL78	CDRL1-1	RASQNIRTYLN
  49A12		VL78
  51E2		VL78
  48F3	815	VL77	CDRL1-2	RASQRISSYLN
  48F8	816	VL49	CDRL1-3	RASQDIGNSLH
  53B9		VL49
  56B4		VL49
  57E7		VL49
  57F11		VL49
  48H11	817	V L40	CDRL1-4	RASQNIRSYLN
  49A10	818	V L65	CDRL1-5	RSSQSLLDSDDGNTYLD
  48D4		V L65
  49C8	819	VL45	CDRL1-6	QASQDINIYLN
  52H1		VL45
  49G2	820	V L66	CDRL1-7	RSSQSLLDSDDGDTYLD
  50C12		V L66
  55G11		V L66
  60D7		VL69
  50G1		V L90
  49G3	821	VL47	CDRL1-8	QASQGISNYLN
  49H12	822	V L43	CDRL1-9	QASQDITKYLN
  51A8	823	VL61	CDRL1-10	TRSSGSIASDYVQ
  51C10.1	824	VL55	CDRL1-11	SGDALPKKYAY
  51C10.2	825	V L70	CDRL1-12	SGDELGDKYAC
  51E5	826	VL79	CDRL1-13	RASQDIRNDLG
  63G8v1		VL104
  64A8		V L1
  67B4		V L1
  68D3		V L2
  51G2	827	VL51	CDRL1-14	RASQGISSWLA
  59A10		VL48
  49H4		VL48
  52A8	828	VL41	CDRL1-15	RASQTISSYLN
  52B8	829	VL82	CDRL1-16	RASQSVSDILA
  52C1	830	VL67	CDRL1-17	SGSSSNIGINYVS
  52C5	831	V L73	CDRL1-18	RASQSISNYLN
  55E4		VL75
  49B11		VL75
  50H10		VL75
  53C1		VL75
  56G1		VL76
  51C1		VL95
  60G5.1		V L74
  52F8	832	VL42	CDRL1-19	RSSQSLLHSNGYNYLD
  52H2	833	VL84	CDRL1-20	RASQSVRSSYLA
  53F6	834	VL63	CDRL1-21	RSSQSLQHSNGYNYLD
  53H5.2	835	VL62	CDRL1-22	RASQGIRNDLG
  50G5 v1		VL93
  66G2		V L12
  53H5.3	836	V L80	CDRL1-23	RASQSVSSNVA
  54A1	837	VL44	CDRL1-24	QASQDISIYLN
  55G9		VL44
  54H10.1	838	V L53	CDRL1-25	RASQSFSSSYLA
  55D1		V L53
  48H3		V L53
  53C11		V L53
  55D3	839	V L71	CDRL1-26	RASQDISNYLA
  50D4		VL92
  55E9	840	VL68	CDRL1-27	RSSQSLLHSNGFNYLD
  55G5	841	VL83	CDRL1-28	SGDNLGDKYAF
  56A7	842	V L52	CDRL1-29	RASQDISSWLA
  56E4		V L52
  56C11	843	V L64	CDRL1-30	GGNDIGSKSVH
  56E7	844	VL86	CDRL1-31	QASQDIKKFLN
  56G3.2	845	V L85	CDRL1-32	RARQSVGSNLI
  56G3.3	846	V L81	CDRL1-33	RASQSVSRDYLA
  55B10		V L81
  61H5		VL88
  52B9		VL88
  57B12	847	V L72	CDRL1-34	RASHDISNYLA
  57D9	848	VL87	CDRL1-35	RASPSVSSSYLA
  53C3.2	849	VL96	CDRL1-36	RASQSISSNLA
  59C9	850	V L50	CDRL1-37	RASQDIDSWLV
  58A5		V L50
  57A4		V L50
  57F9		V L50
  59D10 v1	851	V L56	CDRL1-38	SGDAVPKKYAN
  59D10 v2	852	VL57	CDRL1-39	SGDKLGDKYVC
  65D1		V L27
  59G10.2	853	V L60	CDRL1-40	SGDNLGDKYAC
  59G10.3	854	VL54	CDRL1-41	SGSSSNIGDNYVS
  54H10.3	855	VL97	CDRL1-84	RASQTISIYLN
  60F9	856	VL58	CDRL1-43	RASQRVPSSYIV
  48B4		VL58
  52D6		VL58
  60G5.2	857	VL46	CDRL1-44	SGNKLGDKYVC
  61G5	858	VL59	CDRL1-45	RASQRVPSSYLV
  64E6	859	V L3	CDRL1-46	RASQSVRNSYLA
  65E8		V L3
  65F11		V L3
  67G7		V L3
  63H11		V L3
  66F6		V L15
  63B6	860	V L4	CDRL1-47	RASQSVSNSYLA
  64D4		V L4
  65C3	861	V L5	CDRL1-48	RASQSVSSQLA
  68D5		V L5
  63E6	862	V L6	CDRL1-49	RTSQSISSYLN
  66F7	863	V L7	CDRL1-50	RTSQSISNYLN
  64H5	864	V L8	CDRL1-51	GGNNIGSKNVH
  65G4		V L8
  65E3		V L25
  64H6		VL37
  67G10 v1	865	V L9	CDRL1-52	GGNNIGSKAVH
  63A10 v1		VL22
  63A10v2		VL101
  67G10 v2	866	V L10	CDRL1-53	SGDKLGDKYAC
  63F5	867	V L14	CDRL1-54	RASQTVRNNYLA
  64A7	868	V L17	CDRL1-55	RASQSVSRNYLA
  65C1	869	VL16	CDRL1-56	RASQTIRNSYLA
  66B4	870	V L11	CDRL1-57	RASQGISRWLA
  55A7	871	VL98	CDRL1-58	RASQSISSYLN
  68G5	872	V L13	CDRL1-59	GGNNIGSINVH
  66D4	873	VL18	CDRL1-60	RASQIISRYLN
  65B1	874	VL19	CDRL1-61	RASQNINNYLN
  67A4	875	V L20	CDRL1-62	GGNNIGSKSVH
  65B4	876	VL21	CDRL1-63	GGNNIGSKSVQ
  55E6	877	VL99	CDRL1-64	RASQSVSRSHLA
  65H11	878	V L23	CDRL1-65	GGNNIGSKTVH
  64C8	879	V L24	CDRL1-66	RSSPSLVYSDGNTYLN
  65D4	880	V L26	CDRL1-67	GGNDIGSKNVH
  61E1	881	V L100	CDRL1-68	RASQSIGTFLN
  67G8	882	VL28	CDRL1-69	GGNNIGSYNVF
  65B7	883	VL29	CDRL1-70	RASQSVSSMYLA
  64A6	884	V L30	CDRL1-71	RASQSVNSNLA
  65F9	885	V L31	CDRL1-72	RASQSVSSNLA
  67F5		VL32
  64B10	886	VL33	CDRL1-73	SGSSSNIGNNYVA
  68C8	887	VL34	CDRL1-74	SGSSSNIGNNYVS
  67A5	888	VL35	CDRL1-75	RSSQSLLNSDDGNTYLD
  67C10		VL36
  63F9	889	V L38	CDRL1-76	RASQDIRNDLA
  67F6v1	890	VL39	CDRL1-77	RSSQSLLNSDAGTTYLD
  50G5v2	891	VL94	CDRL1-78	RSSQRLVYSDGNTYLN
  48G4	892	VL89	CDRL1-79	RASQSVASSYLV
  53C3.1		VL89
  58C2	893	VL91	CDRL1-81	RSSQSLFDNDDGDTYLD
  68G8v2	1872	VL105	CDRL1-82	RASQGIRSGLG
  68G8v3		VL106
  65B7v1	1873	VL29	CDRL1-83	RASQSVSSIYLA
  67F6v2	1874	VL108	CDRL1-84	RSSQSLLNSDAGTTYLD
  65B7v2	1875	VL107	CDRL1-85	RSSQSLVYSDGDTYLN
  65H11v2	1876	VL103	CDRL1-86	SGDKLGDRYVC
  63A10v3	1877	VL102	CDRL1-87	SGDKLGNRYTC
  48C9	894	VL78	CDRL2-1	VASSLES
  49A12		VL78
  51E2		VL78
  48F3	895	VL77	CDRL2-2	AVSSLQS
  48F8	896	VL49	CDRL2-3	FASQSFS
  53B9		VL49
  56B4		VL49
  57E7		VL49
  57F11		VL49
  48H11	897	V L40	CDRL2-4	GASNLQS
  49A10	898	V L65	CDRL2-5	TLSYRAS
  48D4		V L65
  49G2		V L66
  50C12		V L66
  55G11		V L66
  60D7		VL69
  67A5		VL35
  67C10		VL36
  50G1		V L90
  58C2		VL91
  49C8	899	VL45	CDRL2-6	DVSNLET
  52H1		VL45
  54A1		VL44
  55G9		VL44
  49G3	900	VL47	CDRL2-7	DASNLET
  56E7		VL86
  49H12	901	V L43	CDRL2-8	DTFILET
  51A8	902	VL61	CDRL2-9	EDKERSS
  51C10.1	903	VL55	CDRL2-10	EDSKRPS
  59D10v1		V L56
  51C10.2	904	V L70	CDRL2-11	QDTKRPS
  59G10.2		V L60
  51E5	905	VL79	CDRL2-12	AASSLQF
  51G2	906	VL51	CDRL2-13	DASSLQS
  52A8	907	VL41	CDRL2-14	AASSLQS
  52C5		V L73
  53H5.2		VL62
  55D3		V L71
  56G1		VL76
  57B12		V L72
  63E6		V L6
  66F7		V L7
  66D4		VL18
  50G5 v1		VL93
  51C1		VL95
  55A7		VL98
  61E1		V L100
  60G5.1		V L74
  52B8	908	VL82	CDRL2-15	GASTRAT
  53H5.3		V L80
  65F9		V L31
  52C1	909	VL67	CDRL2-16	DNNKRPS
  59G10.3		VL54
  68C8		VL34
  52F8	910	VL42	CDRL2-17	LGSNRAS
  55E9		VL68
  52H2	911	VL84	CDRL2-18	GASRRAT
  53F6	912	VL63	CDRL2-19	LDSNRAS
  54H10.1	913	V L53	CDRL2-20	GASSRAT
  55D1		V L53
  48H3		V L53
  53C11		V L53
  57D9		VL87
  61H5		VL88
  52B9		VL88
  63F5		V L14
  64A7		V L17
  65B7		VL29
  55E6		VL99
  55E4	914	VL75	CDRL2-21	TASSLQS
  49B11		VL75
  50H10		VL75
  53C1		VL75
  50G5v2	915	VL94	CDRL2-22	KVSNWDS
  65B7v2
  55G5	916	VL83	CDRL2-23	QDNKRPS
  56A7	917	V L52	CDRL2-24	DASTLQS
  56E4		V L52
  56C11	918	V L64	CDRL2-25	DDSDRPS
  67A4		V L20
  65B4		VL21
  56G3.2	919	V L85	CDRL2-26	GASSRDT
  56G3.3	920	V L81	CDRL2-27	GASARAT
  55B10		V L81
  59A10	921	VL48	CDRL2-28	GASSLQS
  49H4		VL48
  59C9	922	V L50	CDRL2-29	AASNLQR
  58A5		V L50
  57A4		V L50
  57F9		V L50
  63G8v1		V L1
  63G8v2		V L1
  63G8v3		V L1
  64A8		V L2
  67B4
  68D3
  59D10 v2	923	VL57	CDRL2-30	QNNKRPS
  60F9	924	VL58	CDRL2-31	GSSNRAT
  48B4		VL58
  52D6		VL58
  60G5.2	925	VL46	CDRL2-32	QDSKRPS
  65D1		V L27
  65H11v2
  61G5	926	VL59	CDRL2-33	GASNRAT
  64E6	927	V L3	CDRL2-34	GAFSRAS
  65E8		V L3
  65F11		V L3
  67G7		V L3
  63H11		V L3
  63B6	928	V L4	CDRL2-35	GAFSRAT
  64D4		V L4
  65C1		V L16
  66F6		V L15
  48G4		VL89
  53C3.1		VL89
  65C3	929	V L5	CDRL2-36	GASNRAI
  68D5		V L5
  64H5	930	V L8	CDRL2-37	RDSKRPS
  65G4		V L8
  67G8		VL28
  64H6		VL37
  67G10 v1	931	V L9	CDRL2-38	SDSNRPS
  65H11		V L23
  67G10 v2	932	V L10	CDRL2-39	QDNERPS
  66B4	933	V L11	CDRL2-40	AASSLKS
  66G2	934	V L12	CDRL2-41	AASNLQS
  68G5	935	V L13	CDRL2-42	RDRNRPS
  65E3		V L25
  65D4		V L26
  65B1	936	VL19	CDRL2-43	TTSSLQS
  53C3.2	937	VL96	CDRL2-44	GTSIRAS
  63A10v1	938	VL22	CDRL2-45	CDSNRPS
  63A10v2		VL101
  54H10.3	939	VL97	CDRL2-46	SASSLQS
  64C8	940	V L24	CDRL2-47	KGSNWDS
  64A6	941	V L30	CDRL2-48	GTSTRAT
  67F5	942	VL32	CDRL2-49	GSSNRAI
  64B10	943	VL33	CDRL2-50	DNDKRPS
  63F9	944	V L38	CDRL2-51	ASSSLQS
  67F6	945	VL39	CDRL2-52	TLSFRAS
  67F6v2
  50D4	946	VL92	CDRL2-53	AASTLLS
  63A10v3	1878	VL102	CDRL2-54	QDSERPS
  48C9	947	VL78	CDRL3-1	QQSDSIPRT
  49A12
  51E2
  48F3	948	VL77	CDRL3-2	QQSYSATFT
  48F8	949	VL49	CDRL3-3	HQSSDLPLT
  53B9		VL49
  56B4		VL49
  57E7		VL49
  57F11		VL49
  48H11	950	V L40	CDRL3-4	QQSYNTPCS
  49A10	951	V L65	CDRL3-5	MQRIEFPIT
  48D4		V L65
  67C10		VL36
  67F6v1		VL39
  67F6v1		VL39
  49C8	952	VL45	CDRL3-6	QQYDNLPFT
  52H1		VL45
  49G2	953	V L66	CDRL3-7	MQHIEFPST
  50C12		V L66
  55G11		V L66
  49G3	954	VL47	CDRL3-8	HQYDDLPLT
  49H12	955	V L43	CDRL3-9	QQYDNLPLT
  54A1		VL44
  55G9		VL44
  51A8	956	VL61	CDRL3-10	QSYDRNNHVV
  51C10.1	957	VL55	CDRL3-11	YSTDSSVNHVV
  51C10.2	958	V L70	CDRL3-12	QAWDSGTVV
  51E5	959	VL79	CDRL3-13	LQHSSYPLT
  51G2	960	VL51	CDRL3-14	QQTNSFPPWT
  56A7		V L52
  56E4		V L52
  59A10		VL48
  49H4		VL48
  59C9		V L50
  58A5		V L50
  57A4		V L50
  57F9		V L50
  52A8	961	VL41	CDRL3-15	QQSYSTPLT
  65B1		VL19
  52B8	962	VL82	CDRL3-16	QQYNNWPLT
  56G3.2		V L85
  52C1	963	VL67	CDRL3-17	GTWDSSLSAVV
  64B10		VL33
  68C8		VL34
  52C5	964	V L73	CDRL3-18	QQSSSIPWT
  55E4		VL75
  49B11		VL75
  50H10		VL75
  53C1		VL75
  51C1		VL95
  60G5.1		V L74
  52F8	965	VL42	CDRL3-19	MQALQTPFT
  52H2	966	VL84	CDRL3-20	QQYGSSPRS
  53F6	967	VL63	CDRL3-21	MQGLQTPPT
  53H5.2	968	VL62	CDRL3-22	LQHKSYPFT
  53H5.3	969	V L80	CDRL3-23	QQFSNSIT
  54H10.1	970	V L53	CDRL3-24	QQYGSSRT
  55D1		V L53
  48H3		V L53
  53C11		V L53
  55D3	971	V L71	CDRL3-25	QQYNIYPRT
  55E9	972	VL68	CDRL3-26	MQALQTLIT
  55G5	973	VL83	CDRL3-27	QAWDSATVI
  56C11	974	V L64	CDRL3-28	QVWDSSSDVV
  56E7	975	VL86	CDRL3-29	QQYAILPFT
  56G1	976	VL76	CDRL3-30	QQSSTIPWT
  56G3.3	977	V L81	CDRL3-31	QQYGRSLFT
  55B10		V L81
  61H5		VL88
  52B9		VL88
  57B12	978	V L72	CDRL3-32	QQYNTYPRT
  57D9	979	VL87	CDRL3-33	HQYGTSPCS
  59D10 v1	980	V L56	CDRL3-34	YSTDSSGNHVV
  59D10 v2	981	VL57	CDRL3-35	QAWDSSTAV
  59G10.2	982	V L60	CDRL3-36	QAWDSSTTWV
  59G10.3	983	VL54	CDRL3-37	GTWDSSLSVMV
  60D7	984	VL69	CDRL3-38	MQRIEFPLT
  50G1		V L90
  60F9	985	VL58	CDRL3-39	QQYGSSPPWT
  48B4		VL58
  52D6		VL58
  61G5		VL59
  60G5.2	986	VL46	CDRL3-40	QAWDSSTWV
  63G8v1	987	V L1	CDRL3-41	LQHNSYPLT
  63G8v2		V L1
  64A8		V L1
  67B4		V L1
  68D3		V L2
  64E6	988	V L3	CDRL3-42	QQFGSSLT
  65E8		V L3
  65F11		V L3
  67G7		V L3
  63H11		VL3
  63F5		V L14
  65C1		V L16
  66F6		V L15
  63B6	989	V L4	CDRL3-43	QQFGRSFT
  64D4		V L4
  65C3	990	V L5	CDRL3-44	QQYNNWPWT
  68D5		V L5
  63E6	991	V L6	CDRL3-45	QQSYSTSLT
  66F7		V L7
  64H5	992	V L8	CDRL3-46	QVWDSSSVV
  65G4		V L8
  67G10 v1	993	V L9	CDRL3-47	QVWDSSSDGV
  67G10 v2	994	V L10	CDRL3-48	QAWDSTTVV
  64A10v3
  64A7	995	V L17	CDRL3-49	QQYGSSSLCS
  66B4	996	V L11	CDRL3-50	QQANSFPPT
  66G2	997	V L12	CDRL3-51	LQLNGYPLT
  68G5	998	V L13	CDRL3-52	QLWDSSTVV
  66D4	999	VL18	CDRL3-53	QQSYSSPLT
  54H10.3		VL97
  55A7	1000	VL98	CDRL3-54	QQTYSAPFT
  67A4	1001	V L20	CDRL3-55	QVWDSSSDHVV
  65B4		VL21
  63A10	1002	VL22	CDRL3-56	HACGSSSSDGV
  65H11	1003	V L23	CDRL3-57	QVWDSSCDGV
  64C8	1004	V L24	CDRL3-58	IQDTHWPTCS
  65E3	1005	V L25	CDRL3-59	QVWDSSTVV
  67G8		VL28
  65D4	1006	V L26	CDRL3-60	QVWDSNPVV
  65D1	1007	V L27	CDRL3-61	QAWDSRV
  65B7v1	1008	VL29	CDRL3-62	QQYGSSCS
  64A6	1009	V L30	CDRL3-63	QQYNTWPWT
  65F9		V L31
  67F5	1010	VL32	CDRL3-64	QQYEIWPWT
  55E6	1011	VL99	CDRL3-65	QQYGSSPWT
  67A5	1012	VL35	CDRL3-66	MQRLEFPIT
  58C2		VL91
  61E1	1013	V L100	CDRL3-67	QQSFSTPLT
  64H6	1014	VL37	CDRL3-68	QVWDSSPVV
  63F9	1015	V L38	CDRL3-69	LQRNSYPLT
  53C3.2	1016	VL96	CDRL3-70	HQYTNWPRT
  48G4	1017	VL89	CDRL3-71	QQYGTSPFT
  53C3.1		VL89
  50G5 v1	1018	VL93	CDRL3-72	LQHNSYPRT
  50D4	1019	VL92	CDRL3-74	QKYYSAPFT
  50G5 v2	1020	VL94	CDRL3-75	MEGTHWPRD
  63G8v3	1879	VL106	CDRL3-76	LQHNTYPLT
  65B7v2	1880	VL107	CDRL3-77	MQGTHWRGWT
  65H11v2	1881	VL103	CDRL3-78	QAWDSITVV
  63A10v1	1882	VL22	CDRL3-79	QVWDSSSDGV

• TABLE 3C
  Coding Sequences for CDRHs

  	SEQ	Contained
  	ID	in
  Clone	NO:	Reference	Designation	Coding Sequences

  48C9	1021	V H73	CDRH1-1	GGTTACTACTGGACC
  49A12		V H73
  51E2		V H73
  48F3	1022	V H72	CDRH1-2	GGTTACTACTGGAGC
  51E5		V H74
  52C5		V H70
  55E4		V	H70
  60G50.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  56G1		V H71
  51C1		VH89
  48F8	1023	VH48	CDRH1-3	AGCTATAGCATGAAC
  51G2		V H50
  56A7		VH51
  53B9		VH48
  56B4		VH48
  57E7		VH48
  57F11		VH48
  56E4		VH51
  55E6		VH93
  48H11	1024	VH39	CDRH1-4	GGCTACTATAAGCAC
  48G4	1025	VH83	CDRH1-5	GAATTATCCATACAC
  49A10	1026	VH62	CDRH1-6	AACTATGGCATGCAC
  58C2		V H85
  59G10.2		VH57
  48D4		VH62
  49C8	1027	VH44	CDRH1-7	AGTTATGATATCGAC
  52H1
  49G2	1028	VH63	CDRH1-8	AACTATGGCATGCGC
  50C12		VH63
  55G11		VH63
  49G3	1029	VH46	CDRH1-9	AATCCTAGAATGGGTGTGAGC
  49H12	1030	VH42	CDRH1-10	AGTTACGATATCAAC
  54A1		V H43
  55G9		V H43
  50G1	1031	VH84	CDRH1-11	AGCTATGGCCTGCAC
  51A8	1032	VH58	CDRH1-12	AGCTATGGCATGCAC
  52C1		V H64
  53H5.2		VH59
  56C11		VH61
  60D7		V H66
  64H5		V H7
  65G4		V H8
  66G2		V H11
  68G5		V H12
  64C8		V H23
  67G8		V H27
  68D3v2		V H8
  51C10.1	1033	VH54	CDRH1-13	AACTATGCCATGAGC
  59D10v1		VH54
  59D10v2		VH54
  51C10.2	1034	VH67	CDRH1-14	AGTGGTGGTTACTACTGGAGC
  64A6		VH29
  52A8	1035	V H40	CDRH1-15	GGCTACTATTTGCAC
  66B4		V H10
  52B8	1036	VH77	CDRH1-16	TATTATTACTGGAGT
  52F8	1037	VH41	CDRH1-17	GGCTACTATACACAC
  52H2	1038	VH79	CDRH1-18	ACTTACTACTGGAGC
  53F6	1039	V H60	CDRH1-19	ACCTATGGCATGCAC
  53H5.3	1040	VH75	CDRH1-20	GATTACTACTGGAAC
  54H10.1	1041	V H52	CDRH1-21	AGCTATGCCATGAGC
  60F9		VH55
  61G5		V H56
  55D1		V H52
  48H3		V H52
  53C11		V H52
  48B4		VH55
  52D6		VH55
  55D3	1042	VH68	CDRH1-22	AGTGGTGTTTACTACTGGAAC
  55E9	1043	V H65	CDRH1-23	AGCTTTGGCATGCAC
  55G5	1044	VH78	CDRH1-24	AGTTACTACTGGAGC
  65C3		V H5
  68D5		V H5
  67F5		V H31
  55A7		VH92
  56E7	1045	V H81	CDRH1-25	AGCTACTGGATCGGC
  67A5		VH34
  67C10		VH35
  64H6		VH36
  56G3.2	1046	V H80	CDRH1-26	AGTTACTACTGGAAC
  56G3.3	1047	VH76	CDRH1-27	AGTAGTAGTTACTACTGGGGC
  55B10		VH76
  61H5		VH86
  52B9		VH86
  57B12	1048	VH69	CDRH1-28	AGTGGTGTTTACTACTGGAGC
  57D9	1049	VH82	CDRH1-29	AGCAACAGTGCTACTTGGAAC
  59A10	1050	VH47	CDRH1-30	GACTCCTACATGAGC
  49H4
  59C9	1051	VH49	CDRH1-31	AGCTATAGCATGAGT
  58A5		VH49
  57A4		VH49
  57F9		VH49
  59G10.3	1052	V H53	CDRH1-32	CACTATGCCATGAGC
  60G5.2	1053	VH45	CDRH1-33	AACTATGGTATCAGC
  63G8	1054	V H1	CDRH1-34	AGCTATGGCATACAC
  64A8		V H1
  67B4		V H1
  68D3		V H1
  64E6	1055	V H2	CDRH1-35	AGTGGTGATTACTACTGGACC
  65E8		V H2
  65F11		V H2
  67G7		V H2
  63H11		V H3
  63F5		V H13
  65C1		V H15
  66F6		V H14
  63B6	1056	V H4	CDRH1-36	AGTGGTGATTACTACTGGAGC
  64D4		V H4
  65F9		V H30
  64B10v1		VH32
  64B10v1		VH32
  63E6	1057	V H6	CDRH1-37	AGTGGTGATTACTACTGGACC
  66F7		V H6
  50G5 v1		VH88
  50G5 v2		VH88
  67G10v1	1058	V H9	CDRH1-38	AACGCCTGGATGAGT
  67G10v2		V H9
  63A10		VH21
  65H11		VH22
  53C3.2	1059	V H90	CDRH1-39	AGTGGTAATTACTACTGGAGC
  64A7	1060	V H16	CDRH1-40	AGTGATACTTCCTACTGGGGC
  50D4	1061	VH87	CDRH1-41	AGTCATGATATCAAC
  61E1	1062	VH94	CDRH1-42	AGCAACAGTGCTGCTTGGAAC
  66D4	1063	V H17	CDRH1-43	GGCTACTATATACAC
  54H10.3		VH91
  65B1	1064	VH18	CDRH1-44	GGCTACTTTATGCAC
  67A4	1065	VH19	CDRH1-45	ACCTACGACATGCAC
  65B4	1066	V H20	CDRH1-46	AGTTACGACATGCAC
  65E3	1067	V H24	CDRH1-47	AACTATAACATGCAC
  65D4	1068	V H25	CDRH1-48	TTCTATGGCATGCAC
  65D1	1069	V H26	CDRH1-49	TACTATTACATTCAC
  65B7	1070	VH28	CDRH1-50	AGTGATGCTTACTACTGGAGC
  68C8	1071	VH33	CDRH1-51	AGTGGTGATAACTACTGGAGC
  63F9	1072	VH37	CDRH1-52	AGTGGTGGTTACTACTGGAAC
  67F6	1073	V H38	CDRH1-53	GGCTACTGGATCGGC
  48C9	1074	V H73	CDRH2-1	GAAATCAATCATAGTGAAAACACCAACT
  52C5		V H70		ACAACCCGTCCCTCAAGAGT
  55E4		V H70
  56G1		V H71
  49A12		V H73
  51E2		V H73
  60G5.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  51C1		VH89
  48F3	1075	V H72	CDRH2-2	GAAATCACTCATACTGGAAGCTCCAACT
  				ACAACCCGTCCCTCAAGAGT
  48F8	1076	VH48	CDRH2-3	TCCATTAGTAGTAGTAGTAGTTACGAATA
  53B9		VH48		CTACGTAGACTCAGTGAAGGGC
  56B4		VH48
  57E7		VH48
  57F11		VH48
  48H11	1077	VH39	CDRH2-4	TGGATCAACCCTAACAGTGGTGCCACAA
  				AGTATGCACAGAAGTTTCAGGGC
  48G4	1078	VH83	CDRH2-5	GGTTTTGATCCTGAAGATGGTGAAACAA
  53C3.1				TCTACGCACAGAAGTTCCAGGGC
  49A10	1079	VH62	CDRH2-6	ATTATATGGTATGATGGAAGTAATAAAA
  48D4		VH62		ACTATGCAGACTCCGTGAAGGGC
  49C8	1080	VH44	CDRH2-7	TGGATGAACCCTAACGGTGGTAACACAG
  				GCTATGCACAGAAGTTCCAGGGC
  49G2	1081	VH63	CDRH2-8	CTTATATGGTATGATGGAAGTAATAAGTT
  50C12		VH63		CTATGCAGACTCCGTGAAGGGC
  55G11		VH63
  49G3	1082	VH46	CDRH2-9	CACATTTTTTCGAATGACGAAAAATCCTA
  				CAGCACATCTCTGAAGAGC
  49H12	1083	VH42	CDRH2-10	TGGATGAACCCCTACAGTGGGAGCACAG
  				GCTATGCACAGAATTTCCAGGGC
  50G1	1084	VH84	CDRH2-11	GTTATATGGAATGATGGAAGTAATAAGC
  				TTTATGCAGACTCCGTGAAGGGC
  51A8	1085	VH58	CDRH2-12	GTTATATCATATGATGGAAGTAATAAAT
  63G8		V H1		ACTATGCAGACTCCGTGAAGGGC
  64A8		V H1
  67B4		V H1
  68D3		V H1
  51C10.1	1086	VH54	CDRH2-13	GGTATTAGTGGTAGTAGTGCTGGCACAT
  59D10v1		VH54		ACTACGCAGACTCCGTGAAGGGC
  59D10v2		VH54
  51C10.2	1087	VH67	CDRH2-14	TACATCTATTACAATGGGAGTCCCTACGA
  				CAACCCGTCCCTCAAGAGG
  51E5	1088	V H74	CDRH2-15	GAACTCGATCATAGTGGAAGTATCAACT
  				ACAACCCGTCCCTCAAGAGT
  51G2	1089	V H50	CDRH2-16	TCCATTAGTAGTAGTAGTACTTACATATA
  56A7		VH51		CTACGCAGACTCAGTGAAGGGC
  56E4		VH51
  52A8	1090	V H40	CDRH2-17	TGGATCAACCCTAACAGTGCTGCCACAA
  				ACTATGCACCGAAGTTTCAGGGC
  52B8	1091	VH77	CDRH2-18	TATATCTATTATAGTGGGAGCACCAACTA
  55A7		VH92		CAACCCCTCCCTCAAGAGT
  52C1	1092	V H64	CDRH2-19	GTTATATGGTATGATGGAAGTAATAACT
  				ATTATGCAGACTCCGTGAAGGGC
  52F8	1093	VH41	CDRH2-20	TGGATCAACCCTAGCAGTGGTGACACAA
  				AGTATGCACAGAAGTTTCAGGGC
  52H2	1094	VH79	CDRH2-21	TATATCTTTTACAATGGGAACGCCAACTA
  				CAGCCCCTCCCTGAAGAGT
  53F6	1095	V H60	CDRH2-22	GTTATATGGTATGATGGAAGTAATAAAT
  60D7		V H66		ACTATGCAGACTCCGTGAAGGGC
  65D4		V H25
  53H5.2	1096	VH59	CDRH2-23	CTTATATCATATGATGGAAGTAATAAATA
  				CTATGCAGACTCCGTGAAGGGC
  53H5.3	1097	VH75	CDRH2-24	GAAATCAATCATAGTGGAACCACCAACT
  				ACAATCCGTCCCTCAAGAGT
  54A1	1098	V H43	CDRH2-25	TGGATGAACCCTCACAGTGGTAACACAG
  55G9		V H43		GCTATGCACAGAAGTTCCAGGGC
  54H10.1	1099	V H52	CDRH2-26	GCTATTAGTGGTAGTGGTCGTACCACATA
  55D1		V H52		CTCCGCAGACTCCGTGAAGGGC
  48H3		V H52
  53C11		V H52
  55D3	1100	VH68	CDRH2-27	TACCTCTATTACAGTGGGAGCACCTACTA
  				CAACCCGTCCCTCAAGAGT
  55E9	1101	V H65	CDRH2-28	CTTATATGGTATGATGGAGATAATAAAT
  				ACTATGCAGACTCCGTGAAGGGC
  55G5	1102	VH78	CDRH2-29	CGTATCTATATCAGTGGGAGCACCAACT
  				ACAACCCCTCCCTCGAGAAT
  56C11	1103	VH61	CDRH2-30	GTTATATGGTATGATGGAAGTTATCAATT
  				CTATGCAGACTCCGTGAAGGGC
  56E7	1104	V H81	CDRH2-31	ATCATCTATCCTGGTGACTCTGATACCAG
  67A5		VH34		ATACAGCCCGTCCTTCCAAGGC
  67C10		VH35
  67F6		V H38
  56G3.2	1105	V H80	CDRH2-32	CGTATCTATACCAGTGGGAGCACCAACT
  				ACAATCCCTCCCTCAAGAGT
  56G3.3	1106	VH76	CDRH2-33	ATGATCTATTATAGTGGGACCACCTACTA
  				CAACCCGTCCCTCAAGAGT
  57B12	1107	VH69	CDRH2-34	TACATCTATTACAGTGGGAGCACCTACTA
  63H11		V H3		CAACCCGTCCCTCAAGAGT
  66F6		V H14
  65F9		V H30
  57D9	1108	VH82	CDRH2-35	AGGACATACTACAGGTCCAAGTGGTATA
  61E1		VH94		ATGATTATGCAGTATCTGTGAAAAGT
  58C2	1109	V H85	CDRH2-36	GTTATATGGAATGATGGAAATAACAAAT
  				ACTATGCAGACTCCGTGAAGGGC
  59A10	1110	VH47	CDRH2-37	TCCATTAGTAGTAGTGGTAGTATCGTATA
  49H4				CTTCGCAGACTCTGTGAAGGGC
  59C9	1111	VH49	CDRH2-38	TCCATTAGTAGTAGTAGTACTTACATATA
  58A5		VH49		CTACGCAGACTCACTGAAGGGC
  57A4		VH49
  57F9		VH49
  59G10.2	1112	VH57	CDRH2-39	ATTACATCATATGGAGGAAGTAATAAAA
  				ATTATGCAGACTCCGTGAAGGGC
  59G10.3	1113	V H53	CDRH2-40	GCTATTAGTGGTAGTGGTGCTGGCACATT
  				CTACGCGGACTCCATGAAGGGC
  60F9	1114	VH55	CDRH2-41	GTTATTAGTGACAGTGGTGGTAGCACAT
  48B4		VH55		ACTACGCAGACTCCGTGAAGGGC
  52D6		VH55
  60G5.2	1115	VH45	CDRH2-42	TGGATCAGCGCTTACAATGGTTACTCAAA
  				CTATGCACAGAAGTTCCAGGAC
  61G5	1116	V H56	CDRH2-43	GTTATTAGTGGTAGTGGTGGTGACACATA
  				CTACGCAGACTCCGTGAAGGGC
  64E6	1117	V H2	CDRH2-44	TACATCTATTACACTGGGAGCACCTACTA
  65E8		V H2		CAACCCGTCCCTCAAGAGT
  65F11		V H2
  67G7		V H2
  63B6	1118	V H4	CDRH2-45	TACATCTATTACAGTGGGACCACCTACTA
  64D4		V H4		CAACCCGTCCCTCAAGAGT
  65C3	1119	V H5	CDRH2-46	TATATCTATTACACTGGGAGCACCAACTA
  68D5		V H5		CAACCCCTCCCTCAAGAGT
  63E6	1120	V H6	CDRH2-47	TGGATGAACCCTAATAGTGGTGCCACAA
  66F7		V H6		AGTATGCACAGAAGTTTCAGGGC
  64H5	1121	V H7	CDRH2-48	GTTATATGGGATGATGGAAGTAATAAAT
  65G4		V H8		ACTATGCAGACTCCGTGAAGGGC
  67G10v1	1122	V H9	CDRH2-49	CGTATTAAAAGCAAAACTGATGGTGGGA
  67G10v2		V H9		CAACAGAGTACGCTGCACCCGTGAAAGGC
  63F5	1123	V H13	CDRH2-50	TACATCTATTACAGTGGGAGCGCCTACTA
  				CAACCCGTCCCTCAAGAGT
  64A7	1124	V H16	CDRH2-51	AATATCTATTATAGTGGGACCACCTACTT
  				CAACCCGTCCCTCAAGAGT
  65C1	1125	V H15	CDRH2-52	TACATTTTTTACAGTGGGAGCACCTACTA
  65B7		VH28		CAACCCGTCCCTCAAGAGT
  66B4	1126	V H10	CDRH2-53	TGGATCAACCCTAACAGTGGTGGCACAG
  				ACTATGCACAGAAGTTTCAGGGC
  66G2	1127	V H11	CDRH2-54	GGTATATCATATGATGGAAGTAATAAAA
  				ACTATGCAGACTCCGTGAAGGGC
  68G5	1128	V H12	CDRH2-55	GTTATATGGTATGATGGAAGTAATAAAT
  				ACCATGCAGACTCCGTGAAGGGC
  66D4	1129	V H17	CDRH2-56	TGGATCAACCCTCCCAGTGGTGCCACAA
  				ACTATGCACAGAAGTTTCGGGGC
  65B1	1130	VH18	CDRH2-57	TGGATCAACCCTAACAGTGGTGCCACAA
  				ACTATGCACAGAAGTTTCACGGC
  67A4	1131	VH19	CDRH2-58	GCTATTGGTATTGCTGGTGACACATACTA
  				TTCAGACTCCGTGAAGGGC
  65B4	1132	V H20	CDRH2-59	ACTATTGATACTGCTGGTGACGCTTACTA
  				TCCAGGCTCCGTGAAGGGC
  63A10	1133	VH21	CDRH2-60	CGTATTAAAAGCAAAACTGATGGTGGGA
  67G10v1		V H9		CAACAGACTACGCTGCACCCGTGAAAGGC
  67G10v2		V H9
  65H11	1134	VH22	CDRH2-61	CGTATTATAGGCAAAACTGATGGTGGGA
  				CAACAGACTACGCTGCACCCGTGAAAGGC
  64C8	1135	V H23	CDRH2-62	GTTATATCATATGATGGAAGTAACAAAC
  				ACTATGCAGACTCCGTGAAGGGC
  65E3	1136	V H24	CDRH2-63	GTTTTATGGTATGATGGAAATACTAAATA
  				CTATGCAGACTCCGTGAAGGGC
  65D1	1137	V H26	CDRH2-64	CTTATATGGTATGATGGAAGTAATAAAG
  				ACTATGCAGACTCCGTGAAGGGC
  67G8	1138	V H27	CDRH2-65	GTTATATGGTATGATGGAAGTAATAAAG
  				ACTATGCAGACTCCGTGAAGGGC
  64A6	1139	VH29	CDRH2-66	TACATCTATTACAGTGGGGGCACCCACTA
  				CAACCCGTCCCTCAAGAGT
  67F5	1140	V H31	CDRH2-67	TATATCTATTACAGTGGGAACACCAACTA
  				CAACCCCTCCCTCAAGAGT
  64B10	1141	VH32	CDRH2-68	TTTATCTATTACAGTGGGGGCACCAACTA
  				CAACCCCTCCCTCAAGAGT
  68C8	1142	VH33	CDRH2-69	TTCATGTTTTACAGTGGGAGTACCAACTA
  				CAACCCCTCCCTCAAGAGT
  64H6	1143	VH36	CDRH2-70	ATCATCTATCCTGGTGACTCTGAAACCAG
  				ATACAGCCCGTCCTTTCAAGGC
  63F9	1144	VH37	CDRH2-71	TACATCTATGACAGTGGGAGCACCTACT
  				ACAACCCGTCCCTCAAGAGT
  61H5	1145	VH86	CDRH2-72	AGTATCTATTATAGTGGGACCACCTACTA
  52B9		VH86		CAACCCGTCCCTCAAGAGT
  50G5 v1	1146	VH88	CDRH2-73	TGGATCAACCCTGACAGTGGTGGCACAA
  50G5 v2		VH88		ACTATGCACAGAAGTTTCAGGGC
  54H10.3	1147	VH91	CDRH2-74	TGGATCAACCCTAACAGTGGTGGCACAA
  				ACTATGCACAGAAGTTTCGGGGC
  50D4	1148	VH87	CDRH2-75	TGGATGAACCCTTACAGTGGTAGCACAG
  				GCCTCGCACAGAGGTTCCAGGAC
  55E6	1149	VH93	CDRH2-76	TACATTAGTAGTGGTAGTAGTACCATATA
  				CCACGCAGACTCTGTGAAGGGC
  53C3.2	1150	V H90	CDRH2-77	TACATCTATCACAGTGGGAGCGCCTACTA
  				CAACCCGTCCCTCAAGAGT
  64B10v2	1883	VH96	CDRH2-78	TTTATTTATTACAGTGGGGGCACCAACTA
  				CAACCCCCCCCTCAAGAGT
  68D3v2	1884	VH95	CDRH2-79	TTTATATCATATGCTGGAAGTAATAAATA
  				CTATGCAGACTCCGTGAAGGGC
  48C9	1151	V H73	CDRH3-1	GAGAGTGGGAACTTCCCCTTTGACTAC
  49A12		V H73
  51E2		V H73
  48F3	1152	V H72	CDRH3-2	GGCGGGATTTTATGGTTCGGGGAGCAGG
  				CTTTTGATATC
  48F8	1153	VH48	CDRH3-3	TCCCTAAGTATAGCAGTGGCTGCCTCTGA
  53B9		VH48		CTAC
  56B4		VH48
  57E7		VH48
  57F11		VH48
  48H11	1154	VH39	CDRH3-4	GAGGTACCCGACGGTATAGTAGTGGCTG
  				GTTCAAATGCTTTTGATTTC
  48G4	1155	VH83	CDRH3-5	CATTCTGGTTCGGGGAGGTTTTACTACTA
  53C3.1				CTACTACGGTATGGACGTC
  49A10	1156	VH62	CDRH3-6	GATCAGGATTACGATTTTTGGAGTGGTTA
  48D4		VH62		TCCTTACTTCTACTACTACGGTATGGACG
  				TC
  49C8	1157	VH44	CDRH3-7	GGGAAGGAATTTAGCAGGGCGGAGTTTG
  				ACTAC
  49G2	1158	VH63	CDRH3-8	GATCGGTATTACGATTTTTGGAGTGGTTA
  50C12		VH63		TCCATACTTCTTCTACTACGGTCTGGACG
  55G11		VH63		TC
  49G3	1159	VH46	CDRH3-9	GTAGATACCTTGAACTACCACTACTACGG
  				TATGGACGTC
  49H12	1160	VH42	CDRH3-10	TATAATTGGAACTATGGGGCTTTTGATTTC
  54A1		V H43
  55G9		V H43
  50G1	1161	VH84	CDRH3-11	GATCAGTATTACGATTTTTGGAGCGGTTA
  				CCCATACTATCACTACTACGGTATGGACG
  				TC
  51A8	1162	VH58	CDRH3-12	GCGGACGGTGACTACCCATATTACTACTA
  				CTACTACGGTATGGACGTC
  51C10.1	1163	VH54	CDRH3-13	GATTGGAGTATAGCAGTGGCTGGTACTTT
  59D10		VH54		TGACTAC
  v1
  59D10		VH54
  v2
  51C10.2	1164	VH67	CDRH3-14	GGGGCCCTCTACGGTATGGACGTC
  51E5	1165	V H74	CDRH3-15	GTCCTGGGATCTACTCTTGACTAT
  51G2	1166	V H50	CDRH3-16	GATACTTATATCAGTGGCTGGAACTACG
  				GTATGGACGTC
  52A8	1167	V H40	CDRH3-17	GAGGGTGGAACTTACAACTGGTTCGACC
  				CC
  52B8	1168	VH77	CDRH3-18	GGAACTAGGGCTTTTGATATC
  52C1	1169	V H64	CDRH3-19	GATCGGGCGGGAGCCTCTCCCGGAATGG
  				ACGTC
  52C5	1170	V H70	CDRH3-20	GTAACTGGAACGGATGCTTTTGATTTC
  60G5.1		V H70
  49B11		V H70
  50H10		V H70
  53C1		V H70
  51C1		VH89
  55E4		V H70
  56G1		V H71
  52F8	1171	VH41	CDRH3-21	AGTGGCTGGTACCCGTCCTACTACTACGG
  				TATGGACGTC
  52H2	1172	VH79	CDRH3-22	GAAACGGACTACGGTGACTACGCACGTC
  				CTTTTGAATAC
  53F6	1173	V H60	CDRH3-23	GGCCACTATGATAGTAGTGGTCCCAGGG
  				ACTAC
  53H5.2	1174	VH59	CDRH3-24	GAGGCTAACTGGGGCTACAACTACTACG
  				GTATGGACGTC
  53H5.3	1175	VH75	CDRH3-25	ATATTACGATATTTTGACTGGTTAGAATA
  				CTACTTTGACTAC
  61E1	1176	VH94	CDRH3-26	GAGGGCAGCTGGTCCTCCTTCTTTGACTAC
  54H10.1	1177	V H52	CDRH3-27	GAACAGCAGTGGCTGGTTTATTTTGACTAC
  55D1		V H52
  48H3		V H52
  53C11		V H52
  55D3	1178	VH68	CDRH3-28	GATGGTATTACTATGGTTCGGGGAGTTAC
  57B12		VH69		TCACTACTACGGTATGGACGTC
  55E6	1179	VH93	CDRH3-29	GAAGGGTACTATGATAGTAGTGGTTATT
  				ACTACAACGGTATGGACGTC
  55E9	1180	V H65	CDRH3-30	AACAGTGGCTGGGATTACTTCTACTACTA
  				CGGTATGGACGTC
  55G5	1181	VH78	CDRH3-31	AGTGGGAGCTACTCCTTTGACTAC
  56A7	1182	VH51	CDRH3-32	GATATCTATAGCAGTGGCTGGAGCTACG
  56E4		VH51		GTATGGACGTC
  56C11	1183	VH61	CDRH3-33	GATCACGTTTGGAGGACTTATCGTTATAT
  				CTTTGACTAC
  56E7	1184	V H81	CDRH3-34	GCACAACTGGGGATCTTTGACTAC
  50G5 v1	1185	VH88	CDRH3-35	GGCGGATACAGCTATGGTTACGAGGACT
  50G5 v2		VH88		ACTACGGTATGGACGTC
  56G3.2	1186	V H80	CDRH3-36	GGCCCTCTTTGGTTTGACTAC
  56G3.3	1187	VH76	CDRH3-37	GTGGCAGCAGTTTACTGGTATTTCGATCTC
  55B10		VH76
  61H5		VH86
  52B9		VH86
  55A7	1188	VH92	CDRH3-38	GGGATAACTGGAACTATTGACTTC
  57D9	1189	VH82	CDRH3-39	ATTGTAGTAGTACCAGCTGTTCTCTTTGA
  				CTAC
  58C2	1190	V H85	CDRH3-40	GATCAGAATTACGATTTTTGGAATGGTTA
  				TCCCTACTACTTCTACTACGGTATGGACG
  				TC
  59A10	1191	VH47	CDRH3-41	GAGACGTTTAGCAGTGGCTGGTTCGATG
  49H4				CTTTTGATATC
  59C9	1192	VH49	CDRH3-42	GATCGATGGAGCAGTGGCTGGAACGAAG
  58A5		VH49		GTTTTGACTAT
  57A4		VH49
  57F9		VH49
  53C3.2	1193	V H90	CDRH3-43	ACTACGGGTGCTTCTGATATC
  59G10.2	1194	VH57	CDRH3-44	GAGGCCGGGTATAGCTTTGACTAC
  59G10.3	1195	V H53	CDRH3-45	GATCTTAGAATAGCAGTGGCTGGTTCATT
  				TGACTAC
  60D7	1196	V H66	CDRH3-46	GATCTTAGAATAGCAGTGGCTGGTTCATT
  				TGACTAC
  60F9	1197	VH55	CDRH3-47	GATCAGTATTTCGATTTTTGGAGTGGTTA
  48B4		VH55		TCCTTTCTTCTACTACTACGGTATGGACG
  52D6		VH55		TC
  60G5.2	1198	VH45	CDRH3-48	GATCATAGCAGTGGCTGGTACTACTACG
  				GTATGGACGTC
  61G5	1199	V H56	CDRH3-49	GATCATACCAGTGGCTGGTACTACTACG
  				GTATGGACGTC
  63G8	1200	V H1	CDRH3-50	ACGGTGACTAAGGAGGACTACTACTACT
  64A8		V H1		ACGGTATGGACGTC
  67B4		V H1
  68D3		V H1
  66G2		V H11
  64E6	1201	V H2	CDRH3-51	ATGACTACCCCTTACTGGTACTTCGATCTC
  65E8		V H2
  65F11		V H2
  67G7		V H2
  63H11		V H3
  63F5		V H13
  66F6		V H14
  63B6	1202	V H4	CDRH3-52	ATGACTACTCCTTACTGGTACTTCGGTCTC
  64D4		V H4
  65C3	1203	V H5	CDRH3-53	GAATATTACTATGGTTCGGGGAGTTATTA
  68D5		V H5		TCCT
  67F5		V H5
  63E6	1204	V H6	CDRH3-54	GAACTCGGTGACTACCCCTTTTTTGACTAC
  66F7		V H6
  64H5	1205	V H7	CDRH3-55	GAATACGTAGCAGAAGCTGGTTTTGACT
  65G4		V H8		AC
  67G10v1	1206	V H9	CDRH3-56	GATAGTAGTGGGAGCTACTACGTGGAGG
  67G10v2		V H9		ACTACTTTGACTAC
  63A10		VH21
  65H11		VH22
  64A7	1207	V H16	CDRH3-57	CTCCGAGGGGTCTACTGGTACTTCGATCTC
  65C1	1208	V H15	CDRH3-58	ATGACTTCCCCTTACTGGTACTTCGATCTC
  66B4	1209	V H10	CDRH3-59	GACGCAGCAACTGGTCGCTACTACTTTGA
  				CAAC
  68G5	1210	V H12	CDRH3-60	GATCCTGGATACAGCTATGGTCACTTTGA
  				CTAC
  66D4	1211	V H17	CDRH3-61	GAGACTGGAACTTGGAGCTTCTTTGACTAC
  65B1	1212	VH18	CDRH3-62	GAACTGGGGATCTTCAACTGGTTCGACCCC
  67A4	1213	VH19	CDRH3-63	GATCGGAGCAGTGGCCGGTTCGGGGACT
  				ACTACGGTATGGACGTC
  65B4	1214	V H20	CDRH3-64	GATCGGAGCAGTGGCCGGTTCGGGGACT
  				TCTACGGTATGGACGTC
  64C8	1215	V H23	CDRH3-65	GAATTACTATGGTTCGGGGAGTATGGGG
  				TAGACCACGGTATGGACGTC
  65E3	1216	V H24	CDRH3-66	GATGTCTACGGTGACTATTTTGCGTAC
  65D4	1217	V H25	CDRH3-67	GCCCTCAACTGGAACTTTTTTGACTAC
  65D1	1218	V H26	CDRH3-68	GAAGGGACAACTCGACGGGGATTTGACT
  				AC
  67G8	1219	V H27	CDRH3-69	TCAGCAGTGGCTTTGTACAACTGGTTCGA
  				CCCC
  65B7	1220	VH28	CDRH3-70	GAGTCTAGGATATTGTACTTCAACGGGTA
  				CTTCCAGCAC
  64A6	1221	VH29	CDRH3-71	GTCCTCCATTACTCTGATAGTCGTGGTTA
  				CTCGTACTACTCTGACTTC
  65F9	1222	V H30	CDRH3-72	GTCCTCCATTACTATGATAGTAGTGGTTA
  				CTCGTACTACTTTGACTAC
  64B10	1223	VH32	CDRH3-73	TATAGCAGCACCTGGGACTACTATTACG
  				GTGTGGACGTC
  68C8	1224	VH33	CDRH3-74	TATAGGAGTGACTGGGACTACTACTACG
  				GTATGGACGTC
  67A5	1225	VH34	CDRH3-75	CGGGCCTCACGTGGATACAGATTTGGTCT
  				TGCTTTTGCGATC
  67C10	1226	VH35	CDRH3-76	CGGGCCTCACGTGGATACAGATATGGTC
  				TTGCTTTTGCTATC
  64H6	1227	VH36	CDRH3-77	GTAGCAGTGTCTGCCTTCAACTGGTTCGA
  				CCCC
  63F9	1228	VH37	CDRH3-78	GATGTTCTAATGGTGTATACTAAAGGGG
  				GCTACTACTATTACGGTGTGGACGTC
  67F6	1229	V H38	CDRH3-79	CGGGCCTCACGTGGATACAGCTATGGTC
  				ATGCTTTTGATTTC
  50D4	1230	VH87	CDRH3-80	GACCTTAGCAGTGGCTACTACTACTACGG
  				TTTGGACGTG
  54H10.3	1231	VH91	CDRH3-81	GAGGAAGACTACAGTGACCACCACTACT
  				TTGACTAC
  66D4	1885	V H17	CDRH3-82	GAGACTGGAACTTGGAACTTCTTTGACTAC
  68D3v2	1886	VH95	CDRH3-83	ACGGTGACTGAGGAGGACTACTACTACT
  				ACGGTATGGACGTC

• TABLE 3D
  Coding Sequences for CDRLs

  	SEQ	Contained
  	ID	in
  Clone	NO:	Reference	Designation	Coding Sequence

  48C9	1232	VL78	CDRL1-1	CGGGCAAGTCAGAACATTAGGACCT
  49A12				ATTTAAAT
  51E2
  48F3	1233	VL77	CDRL1-2	CGGGCAAGTCAGAGGATTAGCAGTT
  				ATTTAAAT
  48F8	1234	VL49	CDRL1-3	CGGGCCAGTCAGGACATTGGTAATA
  53B9				GCTTACAC
  56B4
  57E7
  57F11
  48H11	1235	V L40	CDRL1-4	CGGGCAAGTCAGAACATTAGGAGCT
  				ATTTAAAT
  49A10	1236	V L65	CDRL1-5	AGGTCTAGTCAGAGCCTCTTGGATAG
  48D4				TGATGATGGAAACACCTATTTGGAC
  49C8	1237	VL45	CDRL1-6	CAGGCGAGTCAGGACATTAACATCTA
  52H1				TTTAAAT
  49G2	1238	V L66	CDRL1-7	AGGTCTAGTCAGAGCCTCTTGGATAG
  50C12		V L66		TGATGATGGAGACACCTATTTGGAC
  55G11		V L66
  50G1		V L90
  60D7		VL69
  49G3	1239	VL47	CDRL1-8	CAGGCGAGTCAGGGCATTAGCAACT
  				ATTTAAAT
  49H12	1240	V L43	CDRL1-9	CAGGCGAGTCAAGACATTACCAAAT
  				ATTTAAAT
  51A8	1241	VL61	CDRL1-10	ACCCGCAGCAGTGGCAGCATTGCCA
  				GCGACTATGTGCAG
  51C10.1	1242	VL55	CDRL1-11	TCTGGAGATGCATTGCCAAAAAAATA
  				TGCTTAT
  51C10.2	1243	V L70	CDRL1-12	TCTGGAGATAAATTGGGGGATAAAT
  				ACGTTTGC
  51E5	1244	VL79	CDRL1-13	CGGGCAAGTCAGGACATTAGAAATG
  63G8v1		V L1		ATTTAGGC
  64A8		V L1
  67B4		V L1
  68D3		V L2
  51G2	1245	VL51	CDRL1-14	CGGGCGAGTCAGGGTATTAGCAGCT
  				GGTTAGCC
  52A8	1246	VL41	CDRL1-15	CGGGCAAGTCAGACTATTAGCAGTTA
  				TTTAAAT
  52B8	1247	VL82	CDRL1-16	AGGGCCAGTCAGAGTGTTAGCGACA
  				TCTTAGCC
  52C1	1248	VL67	CDRL1-17	TCTGGAAGCAGCTCCAACATTGGGAT
  				TAATTATGTATCC
  52C5	1249	V L73	CDRL1-18	CGGGCAAGTCAGAGCATTAGCAACT
  55E4		VL75		ATTTAAAT
  49B11		VL75
  50H10		VL75
  53C1		VL75
  56G1		VL76
  51C1		VL95
  60G5.1		V L74
  52F8	1250	VL42	CDRL1-19	AGGTCTAGTCAGAGCCTCCTGCATAG
  				TAATGGATACAACTATTTGGAT
  52H2	1251	VL84	CDRL1-20	AGGGCCAGTCAGAGTGTTAGAAGCA
  				GCTACTTAGCC
  53F6	1252	VL63	CDRL1-21	AGGTCTAGTCAGAGCCTCCAGCATAG
  				TAATGGATACAACTATTTGGAT
  53H5.2	1253	VL62	CDRL1-22	CGGGCAAGTCAGGGCATTAGAAATG
  50G5 v1		VL93		ATTTAGGC
  53H5.3	1254	V L80	CDRL1-23	AGGGCCAGTCAGAGTGTTAGCAGCA
  				ACGTCGCC
  54A1	1255	VL44	CDRL1-24	CAGGCGAGTCAGGACATTAGCATCTA
  55G9		VL44		TTTAAAT
  54H10.1	1256	V L53	CDRL1-25	AGGGCCAGTCAGAGTTTTAGCAGCA
  55D1		V L53		GTTACTTAGCC
  48H3		V L53
  53C11		V L53
  55D3	1257	V L71	CDRL1-26	CGGGCGAGTCAGGACATTAGCAATT
  50D4		VL92		ATTTAGCC
  55E9	1258	VL68	CDRL1-27	AGGTCTAGTCAGAGCCTCCTGCATAG
  				TAACGGATTCAACTATTTGGAT
  55G5	1259	VL83	CDRL1-28	TCTGGAGACGAATTGGGGGATAAAT
  				ATGCTTGC
  56A7	1260	V L52	CDRL1-29	CGGGCGAGTCAGGATATTAGCAGTTG
  56E4		V L52		GTTAGCC
  56C11	1261	V L64	CDRL1-30	GGGGGAAACGACATTGGAAGTAAAA
  				GTGTGCAC
  56E7	1262	VL86	CDRL1-31	CAGGCGAGTCAGGACATTAAAAAAT
  				TTTTAAAT
  56G3.2	1263	V L85	CDRL1-32	CAGGGCCAGGCAGAGTGTTGGCAGT
  				AACTTAATC
  56G3.3	1264	V L81	CDRL1-33	AGGGCCAGTCAGAGTGTTAGCAGAG
  55B10		V L81		ACTACTTAGCC
  61H5		VL88
  52B9
  57B12	1265	V L72	CDRL1-34	CGGGCGAGTCATGACATTAGCAATTA
  				TTTAGCC
  57D9	1266	VL87	CDRL1-35	AGGGCCAGTCCGAGTGTTAGCAGCA
  				GCTACTTAGCC
  53C3.2	1267	VL96	CDRL1-36	AGGGCCAGTCAGAGTATTAGCAGCA
  				ATTTAGCC
  59C9	1268	V L50	CDRL1-37	CGGGCGAGTCAGGATATTGACAGCT
  58A5		V L50		GGTTAGTC
  57A4		V L50
  57F9		V L50
  59D10	1269	V L56	CDRL1-38	TCTGGAGATGCAGTGCCAAAAAAAT
  v1				ATGCTAAT
  59D10	1270	VL57	CDRL1-39	TCTGGAGATAATTTGGGGGATAAATA
  v2		V	L27		TGCTTGC
  65D1
  59G10.2	1271	V L60	CDRL1-40	TCTGGAGATAATTTGGGGGATAAATA
  				TGCTTTC
  59G10.3	1272	VL54	CDRL1-41	TCTGGAAGCAGCTCCAACATTGGGGA
  				TAATTATGTATCC
  54H10.3	1273	VL97	CDRL1-42	CGGGCAAGTCAGACCATTAGCATCTA
  				TTTAAAT
  60F9	1274	VL58	CDRL1-43	AGGGCCAGTCAGAGGGTTCCCAGCA
  48B4		VL58		GCTACATAGTC
  52D6		VL58
  60G5.2	1275	VL46	CDRL1-44	TCTGGAAATAAATTGGGGGATAAAT
  				ATGTTTGC
  61G5	1276	VL59	CDRL1-45	AGGGCCAGTCAGAGAGTTCCCAGCA
  				GCTACTTAGTC
  64E6	1277	V L3	CDRL1-46	AGGGCCAGTCAGAGTGTTAGGAACA
  65E8		V L3		GCTACTTAGCC
  65F11		V L3
  67G7		V L3
  63H11		V L3
  66F6		V L15
  63B6	1278	V L4	CDRL1-47	AGGGCCAGTCAGAGTGTTAGTAACA
  64D4		V L4		GCTACTTAGCC
  65C3	1279	V L5	CDRL1-48	AGGGCCAGTCAGAGTGTTAGCAGCC
  68D5		V L5		AGTTAGCC
  63E6	1280	V L6	CDRL1-49	CGGACAAGTCAGAGTATTAGCAGCT
  				ATTTAAAT
  66F7	1281	V L7	CDRL1-50	CGGACAAGTCAGAGCATTAGCAACT
  				ATTTAAAT
  64H5	1282	V L8	CDRL1-51	GGGGGAAACAACATTGGAAGTAAAA
  65G4		V L8		ATGTACAC
  65E3		V L25
  64H6		VL37
  67G10	1283	V L9	CDRL1-52	GGGGGAAACAACATTGGAAGTAAAG
  v1				CTGTGCAC
  63A10		VL22
  63A10v2		VL101
  67G10	1284	V L10	CDRL1-53	TCTGGAGATAAATTGGGGGATAAAT
  v2				ATGCTTGC
  63F5	1285	V L14	CDRL1-54	AGGGCCAGTCAGACTGTTAGGAACA
  				ACTACTTAGCC
  64A7	1286	V L17	CDRL1-55	AGGGCCAGTCAGAGTGTTAGTCGCA
  				ACTACTTAGCC
  65C1	1287	V L16	CDRL1-56	AGGGCCAGTCAGACTATTAGGAACA
  				GCTACTTAGCC
  66B4	1288	V L11	CDRL1-57	CGGGCGAGTCAGGGTATTAGCAGGT
  				GGTTAGCC
  55A7	1289	VL98	CDRL1-58	CGGGCAAGTCAGAGCATTAGCAGCT
  				ATTTAAAT
  68G5	1290	V L13	CDRL1-59	GGGGGTAACAACATTGGAAGTATAA
  				ATGTGCAC
  66D4	1291	VL18	CDRL1-60	CGGGCAAGTCAGATCATTAGCAGGT
  				ATTTAAAT
  65B1	1292	VL19	CDRL1-61	CGGGCAAGTCAGAACATTAACAACT
  				ATTTAAAT
  67A4	1293	V L20	CDRL1-62	GGGGGAAACAACATTGGAAGTAAAA
  				GTGTGCAC
  65B4	1294	VL21	CDRL1-63	GGGGGAAACAACATTGGAAGTAAAA
  				GTGTGCAG
  55E6	1295	VL99	CDRL1-64	AGGGCCAGTCAGAGTGTTAGTCGCA
  				GCCACTTAGCC
  65H11	1296	V L23	CDRL1-65	GGGGGAAACAACATTGGAAGTAAAA
  				CTGTGCAC
  64C8	1297	V L24	CDRL1-66	AGGTCTAGTCCAAGCCTCGTATACAG
  				TGATGGAAACACCTACTTGAAT
  65D4	1298	V L26	CDRL1-67	GGGGGAAATGACATTGGAAGTAAAA
  				ATGTGCAC
  61E1	1299	V L100	CDRL1-68	CGGGCAAGTCAGAGCATTGGCACCTT
  				TTTAAAT
  67G8	1300	VL28	CDRL1-69	GGGGGAAACAACATTGGAAGTTACA
  				ATGTGTTC
  65B7	1301	VL29	CDRL1-70	AGGGCCAGTCAGAGTGTTAGCAGCA
  				TGTACTTAGCC
  64A6	1302	V L30	CDRL1-71	AGGGCCAGTCAGAGTGTTAACAGCA
  				ACTTAGCC
  65F9	1303	V L31	CDRL1-72	AGGGCCAGTCAGAGTGTTAGCAGCA
  67F5		VL32		ACTTAGCC
  64B10	1304	VL33	CDRL1-73	TCTGGAAGCAGCTCCAATATTGGGAA
  				TAATTATGTAGCC
  68C8	1305	VL34	CDRL1-74	TCTGGAAGCAGTTCCAACATTGGAAA
  				TAATTATGTATCC
  67A5	1306	VL35	CDRL1-75	AGGTCTAGTCAGAGCCTCTTAAATAG
  67C10		VL36		TGATGATGGAAATACCTATTTGGAC
  63F9	1307	V L38	CDRL1-76	CGGGCAAGTCAGGACATTAGAAATG
  				ATTTAGCC
  67F6v1	1308	VL39	CDRL1-77	AGGTCTAGTCAGAGCCTCTTAAATAG
  67F6v2		VL39		TGATGCTGGTACCACCTATTTGGAC
  50G5 v2	1309	VL94	CDRL1-78	AGGTCTAGTCAAAGACTCGTATACAG
  				TGATGGAAACACCTACTTGAAT
  48G4	1310	VL89	CDRL1-79	AGGGCCAGTCAGAGTGTTGCCAGCA
  53C3.1		VL89		GTTACTTAGTC
  58C2	1311	VL91	CDRL1-81	AGGTCTAGTCAGAGCCTCTTCGATAA
  				TGATGATGGAGACACCTATTTGGAC
  65B7v1	1887	VL29	CDRL1-82	AGGGCCAGTCAGAGTGTTAGCAGCA
  				TCTACTTAGCC
  65B7v2	1888	VL107	CDRL1-83	AGGTCTAGTCAAAGCCTCGTATACAG
  				TGATGGAGACACCTACTTGAAT
  63G8v3	1889	VL106	CDRL1-84	CGGGCAAGTCAGGGCATTAGAAGTG
  63G8v2		VL105		GTTTAGGC
  63A10v3	1890	VL102	CDRL1-85	TCTGGAGATAAATTGGGGAATAGAT
  				ATACTTGC
  65H11v2	1891	V L23	CDRL1-86	TCTGGAGATAAATTGGGGGATAGAT
  				ATGTTTGT
  48C9	1312	VL78	CDRL2-1	GTTGCATCCAGTTTGGAAAGT
  49A12		VL78
  51E2		VL78
  48F3	1313	VL77	CDRL2-2	GCTGTATCCAGTTTGCAAAGT
  48F8	1314	VL49	CDRL2-3	TTTGCTTCCCAGTCCTTCTCA
  53B9		VL49
  56B4		VL49
  57E7		VL49
  57F11		VL49
  48H11	1315	V L40	CDRL2-4	GGTGCATCTAATTTACAGAGT
  49A10	1316	V L65	CDRL2-5	ACGCTTTCCTATCGGGCCTCT
  48D4		V L65
  49G2		V L66
  50C12		V L66
  55G11		V L66
  60D7		VL69
  67A5		VL35
  67C10		VL36
  50G1		V L90
  60D7		VL36
  58C2		VL91
  49C8	1317	VL45	CDRL2-6	GATGTATCCAATTTGGAAACA
  52H1		VL45
  54A1		VL44
  55G9		VL44
  49G3	1318	VL47	CDRL2-7	GATGCATCCAATTTGGAAACA
  56E7		VL86
  49H12	1319	V L43	CDRL2-8	GATACATTCATTTTGGAAACA
  51A8	1320	VL61	CDRL2-9	GAGGATAAAGAAAGATCCTCT
  51C10.1	1321	VL55	CDRL2-10	GAGGACAGCAAACGACCCTCC
  59D10		V L56
  v1
  51C10.2	1322	V L70	CDRL2-11	CAAAATAACAAGCGGCCCTCA
  59G10.2		V L60
  51E5	1323	VL79	CDRL2-12	GCTGCATCCAGTTTGCAATTT
  51G2	1324	VL51	CDRL2-13	GATGCATCCAGTTTGCAAAGT
  52A8	1325	VL41	CDRL2-14	GCTGCATCCAGTTTGCAAAGT
  52C5		V L73
  53H5.2		VL62
  55D3		V L71
  56G1		VL76
  57B12		V L72
  63E6		V L6
  66F7		V L7
  66D4		VL18
  50G5 v1		VL93
  51C1		VL95
  55A7		VL98
  61E1		V L100
  60G5.1		V L74
  52B8	1326	VL82	CDRL2-15	GGTGCATCCACCAGGGCCACT
  53H5.3		V L80
  65F9		V L31
  52C1	1327	VL67	CDRL2-16	GACAATAATAAGCGACCCTCA
  59G10.3		VL54
  68C8		VL34
  52F8	1328	VL42	CDRL2-17	TTGGGTTCTAATCGGGCCTCC
  55E9		VL68
  52H2	1329	VL84	CDRL2-18	GGTGCATCCAGGAGGGCCACT
  53F6	1330	VL63	CDRL2-19	TTGGATTCTAATCGGGCCTCC
  54H10.1	1331	V L53	CDRL2-20	GGTGCATCCAGCAGGGCCACT
  55D1		V L53
  48H3		V L53
  53C11		V L53
  57D9		VL87
  61H5		VL88
  52B9		VL88
  63F5		V L14
  64A7		V L17
  65B7v1		VL29
  55E6		VL99
  55E4	1332	VL75	CDRL2-21	ACAGCTTCCAGTTTGCAAAGT
  49BG11		VL75
  50H10		VL75
  53C1		VL75
  50G5v2	1333	VL94	CDRL2-22	AAGGTTTCTAACTGGGACTCT
  65B7v2		VL107
  55G5	1334	VL83	CDRL2-23	CAAGATACCAAGCGGCCCTCA
  56A7	1335	V L52	CDRL2-24	GATGCATCCACTTTGCAAAGT
  56E4		V L52
  56C11	1336	V L64	CDRL2-25	GATGATAGCGACCGGCCCTCA
  67A4		V L20
  65B4		VL21
  56G3.2	1337	V L85	CDRL2-26	GGTGCATCCAGCAGGGACACT
  56G3.3	1338	V L81	CDRL2-27	GGTGCATCCGCCAGGGCCACT
  55B10		VL81
  59A10	1339	VL48	CDRL2-28	GGTGCATCCAGTTTGCAAAGT
  49H4		VL48
  59C9	1340	V L50	CDRL2-29	GCTGCATCCAATTTGCAAAGA
  58A5		V L50
  57A4		V L50
  57F9		V L50
  63G8v1		VL104
  63GBv2		VL105
  63G8v3		VL106
  64A8		V L1
  67B4		V L1
  68D3		V L1
  59D10	1341	VL57	CDRL2-30	CAAGATACCAAGCGGCCCTCA
  v2
  60F9	1342	VL58	CDRL2-31	GGTTCATCCAACAGGGCCACT
  48B4		VL58
  52D6		VL58
  60G5.2	1343	VL46	CDRL2-32	CAAGATAGCAAGCGGCCCTCA
  65D1		V L27
  65H11v2		VL103
  61G5	1344	VL59	CDRL2-33	GGTGCATCCAACAGGGCCACA
  64E6	1345	V L3	CDRL2-34	GGTGCATTTAGCAGGGCCTCT
  65E8		V L3
  65F11		V L3
  67G7		V L3
  63H11		V L3
  63B6	1346	V L4	CDRL2-35	GGTGCATTCAGTAGGGCCACT
  64D4		V L4
  65C1		V L16
  66F6		V L15
  48G4		VL83
  53C3.1		VL83
  65C3	1347	V L5	CDRL2-36	GGTGCCTCCAACAGGGCCATT
  68D5		V L5
  64H5	1348	V L8	CDRL2-37	AGGGATAGCAAGCGGCCCTCT
  65G4		V L8
  67G8		VL28
  64H6		VL37
  67G10	1349	V L9	CDRL2-38	AGCGATAGCAACCGGCCCTCA
  v1
  65H11		V L23
  67G10	1350	V L10	CDRL2-39	CAAGATAACGAGCGGCCCTCA
  v2
  66B4	1351	V L11	CDRL2-40	GCTGCATCCAGTTTGAAAAGT
  66G2	1352	V L12	CDRL2-41	GCTGCATCCAATTTGCAAAGT
  68G5	1353	V L13	CDRL2-42	AGGGATAGGAACCGGCCCTCT
  65E3		V L25
  65D4		V L26
  65B1	1354	VL19	CDRL2-43	ACTACATCCAGTTTGCAAAGT
  53C3.2	1355	VL96	CDRL2-44	GGTACATCCATCAGGGCCAGT
  63A10v1	1356	VL22	CDRL2-45	TGTGATAGCAACCGGCCCTCA
  63A10v2		VL101
  54H10.3	1357	VL97	CDRL2-46	TCTGCATCCAGTTTGCAAAGT
  64C8	1358	V L24	CDRL2-47	AAGGGTTCTAACTGGGACTCA
  64A6	1359	V L30	CDRL2-48	GGTACATCCACCAGGGCCACT
  67F5	1360	VL32	CDRL2-49	GGTTCATCCAACAGGGCCATT
  64B10	1361	VL33	CDRL2-50	GACAATGATAAGCGACCCTCA
  63F9	1362	V L38	CDRL2-51	GCTTCATCCAGTTTGCAAAGT
  67F6v2	1363	VL39	CDRL2-52	ACGCTTTCCTTTCGGGCCTCT
  50D4	1364	VL92	CDRL2-53	GCTGCATCCACTTTGCTATCA
  68A10v3	1892	VL102	CDRL2-54	CAAGATAGCGAGCGGCCCTCA
  48C9	1365	VL78	CDRL3-1	CAACAGAGTGACAGTATCCCTCGGACG
  49A12
  51E2
  48F3	1366	VL77	CDRL3-2	CAACAGAGTTACAGTGCTACATTCACT
  48F8	1367	VL49	CDRL3-3	CATCAGAGTAGTGATTTACCGCTCACT
  53B9		VL49
  56B4		VL49
  57E7		VL49
  57F11		VL49
  48H11	1368	V L40	CDRL3-4	CAACAGAGTTACAATACCCCGTGCAGT
  49A10	1369	V L65	CDRL3-5	ATGCAACGTATAGAGTTTCCGATCACC
  48D4		V L65
  67F6v2		VL108
  49C8	1370	VL45	CDRL3-6	CAACAATATGATAATCTCCCATTCACT
  52H1		VL45
  67C10		VL36
  67F6v1		VL39
  49G2	1371	V L66	CDRL3-7	ATGCAACATATAGAATTTCCTTCGACC
  50C12		V L66
  55G11		V L66
  49G3	1372	VL47	CDRL3-8	CACCAGTATGATGATCTCCCGCTCACT
  49H12	1373	V L43	CDRL3-9	CAACAGTATGACAATTTACCGCTCACC
  54A1		VL44
  55G9		VL44
  51A8	1374	VL61	CDRL3-10	CAGTCTTATGATCGCAACAATCATGT
  				GGTT
  51C10.1	1375	VL55	CDRL3-11	TACTCAACAGACAGCAGTGTTAATCA
  				TGTGGTA
  51C10.2	1376	V L70	CDRL3-12	CAGGCGTGGGATAGTAGTACTGCGGTA
  51E5	1377	VL79	CDRL3-13	CTACAACATAGTAGTTACCCGCTCACT
  51G2	1378	VL51	CDRL3-14	CAACAGACTAACAGTTTCCCTCCGTG
  56A7		V L52		GACG
  56E4		V L52
  59A10		VL48
  49H4		VL48
  59C9		V L50
  58A5		V L50
  57A4		V L50
  57F9		V L50
  52A8	1379	VL41	CDRL3-15	CAGCAGAGTTACAGTACCCCGCTCACT
  65B1		VL19
  52B8	1380	VL82	CDRL3-16	CAGCAGTATAATAACTGGCCGCTCACT
  56G3.2		V L85
  52C1	1381	VL67	CDRL3-17	GGAACATGGGATAGCAGCCTGAGTG
  64B10		VL33		CTGTGGTA
  68C8		VL34
  52C5	1382	V L73	CDRL3-18	CAACAGAGTTCCAGTATCCCTTGGACG
  55E4		VL75
  49B11		VL75
  50H10		VL75
  53C1		VL75
  51C1		VL95
  60G5.1		V L74
  52F8	1383	VL42	CDRL3-19	ATGCAAGCTCTACAAACTCCATTCACT
  52H2	1384	VL84	CDRL3-20	CAGCAGTATGGTAGTTCACCTCGCAGT
  53F6	1385	VL63	CDRL3-21	ATGCAAGGTCTACAAACTCCTCCCACT
  53H5.2	1386	VL62	CDRL3-22	CTACAGCATAAGAGTTACCCATTCACT
  53H5.3	1387	V L80	CDRL3-23	CAGCAGTTTAGTAACTCAATCACC
  54H10.1	1388	V L53	CDRL3-24	CAGCAGTATGGTAGCTCACGGACG
  55D1		V L53
  48H3		V L53
  53C11		V L53
  55D3	1389	V L71	CDRL3-25	CAACAGTATAATATTTACCCTCGGACG
  55E9	1390	VL68	CDRL3-26	ATGCAAGCTCTACAAACTCTCATCACC
  55G5	1391	VL83	CDRL3-27	CAGGCGTGGGACAGCGGCACTGTGG
  				TA
  56C11	1392	V L64	CDRL3-28	CAGGTGTGGGATAGTAGTAGTGATGT
  				GGTA
  56E7	1393	VL86	CDRL3-29	CAACAATATGCTATTCTCCCATTCACT
  56G1	1394	VL76	CDRL3-30	CAACAGAGTTCCACTATCCCTTGGACG
  56G3.3	1395	V L81	CDRL3-31	CAGCAATATGGTAGATCACTATTCACT
  55B10		V L81
  61H5		VL88
  52B9		VL88
  57B12	1396	V L72	CDRL3-32	CAACAATATAATACTTACCCTCGGACG
  57D9	1397	VL87	CDRL3-33	CATCAGTATGGTACCTCACCGTGCAGT
  59D10	1398	V L56	CDRL3-34	TACTCAACAGACAGCAGTGGTAATCA
  v1				TGTGGTA
  59D10	1399	VL57	CDRL3-35	CAGGCGTGGGACAGCAGCACTACAT
  v2				GGGTG
  59G10.2	1400	V L60	CDRL3-36	CAGGCGTGGGACAGCGCCACTGTGA
  				TT
  59G10.3	1401	VL54	CDRL3-37	GGAACATGGGACAGCAGCCTGAGTG
  				TTATGGTT
  60D7	1402	VL69	CDRL3-38	ATGCAACGTATAGAGTTTCCGCTCACT
  50G1		V L90
  60F9	1403	VL58	CDRL3-39	CAGCAGTATGGTAGCTCACCTCCGTG
  48B4		VL58		GACG
  52D6		VL58
  61G5		VL59
  60G5.2	1404	VL46	CDRL3-40	CAGGCGTGGGACAGCAGCACTTGGG
  				TG
  63G8v1	1405	VL104	CDRL3-41	CTCCAGCATAATAGTTACCCTCTCACT
  63G8v2		VL105
  64A8		V L1
  67B4		V L1
  68D3		V L2
  64E6	1406	V L3	CDRL3-42	CAGCAGTTTGGAAGCTCACTCACT
  65E8		V L3
  65F11		V L3
  67G7		V L3
  63H11		VL
  63F5		V L14
  65C1		V L16
  66F6		V L15
  63B6	1407	V L4	CDRL3-43	CAGCAGTTTGGTAGGTCATTCACT
  64D4		V L4
  65C3	1408	V L5	CDRL3-44	CAGCAGTATAATAACTGGCCGTGGACG
  68D5		V L5
  63E6	1409	V L6	CDRL3-45	CAACAGAGTTACAGTACCTCGCTCACT
  66F7		V L7
  64H5	1410	V L8	CDRL3-46	CAGGTGTGGGACAGCAGTAGTGTGG
  65G4		V L8		TA
  67G10	1411	V L9	CDRL3-47	CAGGTGTGGGACAGTAGTAGTGATG
  v1				GGGTA
  67G10	1412	V L10	CDRL3-48	CAGGCGTGGGACAGCACCACTGTGG
  v2				TA
  63A10v2		VL101
  63A10v3		VL102
  64A7	1413	V L17	CDRL3-49	CAGCAGTATGGTAGTTCATCTCTGTG
  				CAGT
  66B4	1414	V L11	CDRL3-50	CAACAGGCTAACAGTTTCCCTCCGACG
  66G2	1415	V L12	CDRL3-51	CTACAACTTAATGGTTACCCTCTCACT
  68G5	1416	V L13	CDRL3-52	CAGTTGTGGGACAGCAGCACTGTGGTT
  66D4	1417	VL18	CDRL3-53	CAACAGAGTTACAGTTCCCCGCTCACT
  54H10.3		VL97
  55A7	1418	VL98	CDRL3-54	CAACAGACTTACAGTGCCCCATTCACT
  67A4	1419	V L20	CDRL3-55	CAGGTGTGGGATAGTAGTAGTGATCA
  65B4		VL21		TGTGGTA
  63A10	1420	VL22	CDRL3-56	CATGCGTGTGGGAGCAGTAGTAGCG
  				ATGGGGTA
  65H11	1421	V L23	CDRL3-57	CAGGTGTGGGACAGTAGTTGTGATGG
  				GGTA
  64C8	1422	V L24	CDRL3-58	ATACAAGATACACACTGGCCCACGTG
  				CAGT
  65E3	1423	V L25	CDRL3-59	CAGGTGTGGGACAGCAGCACTGTGG
  67G8		VL28		TC
  65D4	1424	V L26	CDRL3-60	CAGGTGTGGGACAGCAACCCTGTGGTA
  65D1	1425	V L27	CDRL3-61	CAGGCGTGGGACAGCAGGGTA
  65B7v1	1426	VL29	CDRL3-62	CAGCAGTATGGTAGCTCGTGCAGT
  64A6	1427	V L30	CDRL3-63	CAGCAATATAATACCTGGCCGTGGACG
  65F9		V L31
  67F5	1428	VL32	CDRL3-64	CAGCAGTATGAAATTTGGCCGTGGACG
  55E6	1429	VL99	CDRL3-65	CAGCAGTATGGTAGTTCACCGTGGACG
  67A5	1430	VL35	CDRL3-66	ATGCAACGTCTAGAGTTTCCTATTACC
  58C2		VL91
  61E1	1431	V L100	CDRL3-67	CAACAGAGTTTCAGTACCCCGCTCACT
  64H6	1432	VL37	CDRL3-68	CAGGTGTGGGACAGCAGTCCTGTGGTA
  63F9	1433	V L38	CDRL3-69	CTACAGCGTAATAGTTACCCGCTCACT
  53C3.2	1434	VL96	CDRL3-70	CACCAGTATACTAACTGGCCTCGGACG
  48G4	1435	VL89	CDRL3-71	CAGCAGTATGGTACCTCACCATTTACT
  53C3.1		VL89
  50G5 v1	1436	VL93	CDRL3-72	CTACAGCATAATAGTTACCCTCGGACG
  64B10v2	1893	VL33	CDRL3-73	TATAGCAGCACCTGGGACTACTATTA
  				CGGTGTGGACGTC
  50D4	1437	VL92	CDRL3-74	CAAAAGTATTACAGTGCCCCTTTCACT
  50G5 v2	1438	VL94	CDRL3-75	ATGGAAGGTACACACTGGCCTCGGG
  				AC
  63G8v3	1894	VL106	CDRL3-76	CTCCAACATAATACTTACCCTCTCACT
  65B7v2	1895	VL107	CDRL3-77	ATGCAAGGTACACACTGGCGGGGTT
  				GGACG
  65H11v2	1896	VL103	CDRL3-78	CAGGCGTGGGACAGCATCACTGTGGTA
  63A10v1	1897	VH21	CDRL3-79	CAGGTGTGGGACAGTAGTAGTGATG
  				GGGTA

• The structure and properties of CDRs within a naturally occurring antibody has been described, supra. Briefly, in a traditional antibody, the CDRs are embedded within a framework in the heavy and light chain variable region where they constitute the regions responsible for antigen binding and recognition. A variable region comprises at least three heavy or light chain CDRs, see, e.g., Kabat et al., (1991) “Sequences of Proteins of Immunological Interest”, 5th Ed., US Dept. of Health and Human Services, PHS, NIH, NIH Publication no. 91-3242; see also Chothia and Lesk, (1987) J. Mol. Biol. 196:901-917; Chothia et al., (1989) Nature 342: 877-883), within a framework region (designated framework regions 1-4, FR1, FR2, FR3, and FR4, by Kabat et al., (1991); see also Chothia and Lesk, (1987) supra). The CDRs provided herein, however, can not only be used to define the antigen binding domain of a traditional antibody structure, but can be embedded in a variety of other polypeptide structures, as described herein.
• In one aspect, the CDRs provided are (a) a CDRH selected from the group consisting of (i) a CDRH1 selected from the group consisting of SEQ ID NOS 603-655; (ii) a CDRH2 selected from the group consisting of SEQ ID NOS 656-732; (iii) a CDRH3 selected from the group consisting of SEQ ID NOS 733-813; and (iv) a CDRH of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than five, four, three, two, or one amino acids; (B) a CDRL selected from the group consisting of (i) a CDRL1 selected from the group consisting of SEQ ID NOS 814-893; (ii) a CDRL2 selected from the group consisting of SEQ ID NOS 894-946; (iii) a CDRL3 selected from the group consisting of SEQ ID NOS 947-1020; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 1, 2, 3, 4, or 5 amino acids amino acids.
• In another aspect, an antigen binding protein comprises 1, 2, 3, 4, 5, or 6 variant forms of the CDRs listed in Tables 3A and 3B, infra, each having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to a CDR sequence listed in Tables 3A and 3B, infra. Some antigen binding proteins comprise 1, 2, 3, 4, 5, or 6 of the CDRs listed in Tables 3A and 3B, infra, each differing by no more than 1, 2, 3, 4 or 5 amino acids from the CDRs listed in these tables.
• In still another aspect, an antigen binding protein includes the following associations of CDRL1, CDRL2 and CDRL3, presented for convenience in tabular form and in reference to the clone source of the association:

• TABLE 4
  CDRL Associations

  	Clone ID	CDRL1	CDRL2	CDRL3
  	63G8	CDRL1-13	CDRL2-29	CDRL3-41
  	64A8	CDRL1-13	CDRL2-29	CDRL3-41
  	67B4	CDRL1-13	CDRL2-29	CDRL3-41
  	68D3	CDRL1-13	CDRL2-29	CDRL3-41
  	64E6	CDRL1-46	CDRL2-34	CDRL3-42
  	65E8	CDRL1-46	CDRL2-34	CDRL3-42
  	65F11	CDRL1-46	CDRL2-34	CDRL3-42
  	67G7	CDRL1-46	CDRL2-34	CDRL3-42
  	63B6	CDRL1-47	CDRL2-3	CDRL3-43
  	64D4	CDRL1-47	CDRL2-3	CDRL3-43
  	65C3	CDRL1-48	CDRL2-36	CDRL3-44
  	68D5	CDRL1-48	CDRL2-36	CDRL3-44
  	63E6	CDRL1-49	CDRL2-14	CDRL3-45
  	66F7	CDRL1-50	CDRL2-14	CDRL3-45
  	64H5	CDRL1-51	CDRL2-37	CDRL3-46
  	65G4	CDRL1-51	CDRL2-37	CDRL3-46
  	67G10v1	CDRL1-52	CDRL2-38	CDRL3-47
  	67G10v2	CDRL1-53	CDRL2-39	CDRL3-48
  	66B4	CDRL1-57	CDRL2-40	CDRL3-50
  	66G2	CDRL1-22	CDRL2-41	CDRL3-51
  	68G5	CDRL1-59	CDRL2-42	CDRL3-52
  	63F5	CDRL1-54	CDRL2-20	CDRL3-42
  	66F6	CDRL1-46	CDRL2-35	CDRL3-42
  	65C1	CDRL1-56	CDRL2-35	CDRL3-42
  	64A7	CDRL1-55	CDRL2-20	CDRL3-49
  	66D4	CDRL1-60	CDRL2-14	CDRL3-53
  	65B1	CDRL1-61	CDRL2-43	CDRL3-15
  	67A4	CDRL1-62	CDRL2-25	CDRL3-55
  	65B4	CDRL1-63	CDRL2-25	CDRL3-55
  	63A10	CDRL1-52	CDRL2-45	CDRL3-56
  	65H11	CDRL1-65	CDRL2-38	CDRL3-57
  	64C8	CDRL1-66	CDRL2-47	CDRL3-58
  	65E3	CDRL1-51	CDRL2-42	CDRL3-59
  	65D4	CDRL1-67	CDRL2-42	CDRL3-60
  	65D1	CDRL1-39	CDRL2-32	CDRL3-61
  	67G8	CDRL1-69	CDRL2-37	CDRL3-59
  	65B7	CDRL1-70	CDRL2-20	CDRL3-62
  	64A6	CDRL1-71	CDRL2-48	CDRL3-63
  	65F9	CDRL1-72	CDRL2-15	CDRL3-63
  	67F5	CDRL1-72	CDRL2-49	CDRL3-64
  	64B10	CDRL1-73	CDRL2-50	CDRL3-17
  	68C8	CDRL1-74	CDRL2-16	CDRL3-17
  	67A5	CDRL1-75	CDRL2-5	CDRL3-66
  	67C10	CDRL1-75	CDRL2-5	CDRL3-5
  	64H6	CDRL1-51	CDRL2-37	CDRL3-68
  	63F9	CDRL1-76	CDRL2-51	CDRL3-69
  	67F6	CDRL1-77	CDRL2-52	CDRL3-5
  	48H11	CDRL1-4	CDRL2-4	CDRL3-4
  	52A8	CDRL1-15	CDRL2-14	CDRL3-15
  	52F8	CDRL1-19	CDRL2-17	CDRL3-19
  	49H12	CDRL1-9	CDRL2-8	CDRL3-9
  	54A1	CDRL1-24	CDRL2-6	CDRL3-9
  	55G9	CDRL1-24	CDRL2-6	CDRL3-9
  	49C8	CDRL1-6	CDRL2-6	CDRL3-6
  	52H1	CDRL1-6	CDRL2-6	CDRL3-6
  	60G5.2	CDRL1-44	CDRL2-32	CDRL3-40
  	49G3	CDRL1-8	CDRL2-7	CDRL3-8
  	59A10	CDRL1-14	CDRL2-28	CDRL3-14
  	49H4	CDRL1-14	CDRL2-28	CDRL3-14
  	48F8	CDRL1-3	CDRL2-3	CDRL3-3
  	53B9	CDRL1-3	CDRL2-3	CDRL3-3
  	56B4	CDRL1-3	CDRL2-3	CDRL3-3
  	57E7	CDRL1-3	CDRL2-3	CDRL3-3
  	57F11	CDRL1-3	CDRL2-3	CDRL3-3
  	59C9	CDRL1-37	CDRL2-29	CDRL3-14
  	58A5	CDRL1-37	CDRL2-29	CDRL3-14
  	57A4	CDRL1-37	CDRL2-29	CDRL3-14
  	57F9	CDRL1-37	CDRL2-29	CDRL3-14
  	51G2	CDRL1-14	CDRL2-13	CDRL3-14
  	56A7	CDRL1-29	CDRL2-24	CDRL3-14
  	56E4	CDRL1-29	CDRL2-24	CDRL3-14
  	54H10.1	CDRL1-25	CDRL2-20	CDRL3-24
  	55D1	CDRL1-25	CDRL2-20	CDRL3-24
  	48H3	CDRL1-25	CDRL2-20	CDRL3-24
  	53C11	CDRL1-25	CDRL2-20	CDRL3-24
  	59G10.3	CDRL1-41	CDRL2-16	CDRL3-37
  	51C10.1	CDRL1-12	CDRL2-10	CDRL3-11
  	59D10 v1	CDRL1-38	CDRL2-10	CDRL3-34
  	59D10 v2	CDRL1-39	CDRL2-30	CDRL3-35
  	60F9	CDRL1-43	CDRL2-31	CDRL3-39
  	48B4	CDRL1-43	CDRL2-31	CDRL3-39
  	52D6	CDRL1-43	CDRL2-31	CDRL3-39
  	61G5	CDRL1-45	CDRL2-33	CDRL3-39
  	59G10.2	CDRL1-40	CDRL2-11	CDRL3-36
  	51A8	CDRL1-10	CDRL2-9	CDRL3-10
  	53H5.2	CDRL1-22	CDRL2-14	CDRL3-22
  	53F6	CDRL1-21	CDRL2-19	CDRL3-21
  	56C11	CDRL1-30	CDRL2-25	CDRL3-28
  	49A10	CDRL1-5	CDRL2-5	CDRL3-5
  	48D4	CDRL1-5	CDRL2-5	CDRL3-5
  	49G2	CDRL1-7	CDRL2-5	CDRL3-7
  	50C12	CDRL1-7	CDRL2-5	CDRL3-7
  	55G11	CDRL1-7	CDRL2-5	CDRL3-7
  	52C1	CDRL1-17	CDRL2-16	CDRL3-17
  	55E9	CDRL1-27	CDRL2-17	CDRL3-26
  	60D7	CDRL1-1	CDRL2-5	CDRL3-38
  	51C10.2	CDRL1-12	CDRL2-11	CDRL3-12
  	55D3	CDRL1-26	CDRL2-14	CDRL3-25
  	57B12	CDRL1-34	CDRL2-14	CDRL3-32
  	52C5	CDRL1-18	CDRL2-14	CDRL3-18
  	55E4	CDRL1-18	CDRL2-21	CDRL3-18
  	49B11	CDRL1-18	CDRL2-21	CDRL3-18
  	50H10	CDRL1-18	CDRL2-21	CDRL3-18
  	53C1	CDRL1-18	CDRL2-21	CDRL3-18
  	56G1	CDRL1-18	CDRL2-14	CDRL3-30
  	48F3	CDRL1-2	CDRL2-2	CDRL3-2
  	48C9	CDRL1-1	CDRL2-1	CDRL3-1
  	49A12	CDRL1-1	CDRL2-1	CDRL3-1
  	51E2	CDRL1-1	CDRL2-1	CDRL3-1
  	51E5	CDRL1-13	CDRL2-12	CDRL3-13
  	53H5.3	CDRL1-23	CDRL2-15	CDRL3-23
  	56G3.3	CDRL1-33	CDRL2-27	CDRL3-31
  	55B10	CDRL1-33	CDRL2-27	CDRL3-31
  	52B8	CDRL1-16	CDRL2-15	CDRL3-16
  	55G5	CDRL1-28	CDRL2-23	CDRL3-27
  	52H2	CDRL1-20	CDRL2-18	CDRL3-20
  	56G3.2	CDRL1-32	CDRL2-26	CDRL3-16
  	56E7	CDRL1-31	CDRL2-7	CDRL3-29
  	57D9	CDRL1-35	CDRL2-20	CDRL3-33
  	61H5	CDRL1-33	CDRL2-20	CDRL3-31
  	52B9	CDRL1-33	CDRL2-20	CDRL3-31
  	48G4	CDRL1-79	CDRL2-35	CDRL3-71
  	53C3.1	CDRL1-79	CDRL2-35	CDRL3-71
  	50G1	CDRL1-7	CDRL2-5	CDRL3-38
  	58C2	CDRL1-81	CDRL2-5	CDRL3-66
  	60G5.1	CDRL1-18	CDRL2-14	CDRL3-18
  	54H10.3	CDRL1-42	CDRL2-46	CDRL3-53
  	50G5 v1	CDRL1-22	CDRL2-14	CDRL3-72
  	50G5 v2	CDRL1-78	CDRL2-22	CDRL3-75
  	51C1	CDRL1-18	CDRL2-14	CDRL3-18
  	53C3.2	CDRL1-36	CDRL2-44	CDRL3-70
  	50D4	CDRL1-26	CDRL2-53	CDRL3-74
  	55A7	CDRL1-58	CDRL2-14	CDRL3-54
  	55E6	CDRL1-64	CDRL2-20	CDRL3-65
  	61E1	CDRL1-68	CDRL2-14	CDRL3-67
  	63H11	CDRL1-46	CDRL2-34	CDRL3-42

• In an additional aspect, an antigen binding protein includes the following associations of CDRH1, CDRH2 and CDRH3, presented for convenience in tablular form and in reference to the clone source of the association:

• TABLE 5
  CDRH Associations

  	Clone ID	CDRH1	CDRH2	CDRH3
  	63G8	CDRH1-34	CDRH2-12	CDRH3-50
  	64A8	CDRH1-34	CDRH2-12	CDRH3-50
  	67B4	CDRH1-34	CDRH2-12	CDRH3-50
  	68D3	CDRH1-34	CDRH2-12	CDRH3-50
  	64E6	CDRH1-35	CDRH2-44	CDRH3-51
  	65E8	CDRH1-35	CDRH2-44	CDRH3-51
  	65F11	CDRH1-35	CDRH2-44	CDRH3-51
  	67G7	CDRH1-35	CDRH2-44	CDRH3-51
  	63B6	CDRH1-36	CDRH2-45	CDRH3-52
  	64D4	CDRH1-36	CDRH2-45	CDRH3-52
  	65C3	CDRH1-24	CDRH2-46	CDRH3-53
  	68D5	CDRH1-24	CDRH2-46	CDRH3-53
  	63E6	CDRH1-37	CDRH2-47	CDRH3-54
  	66F7	CDRH1-37	CDRH2-47	CDRH3-54
  	64H5	CDRH1-12	CDRH2-48	CDRH3-55
  	65G4	CDRH1-12	CDRH2-48	CDRH3-55
  	67G10v1	CDRH1-38	CDRH2-49	CDRH3-56
  	67G10v2	CDRH1-38	CDRH2-49	CDRH3-56
  	66B4	CDRH1-15	CDRH2-53	CDRH3-59
  	66G2	CDRH1-12	CDRH2-54	CDRH3-50
  	68G5	CDRH1-12	CDRH2-55	CDRH3-60
  	63F5	CDRH1-35	CDRH2-50	CDRH3-51
  	66F6	CDRH1-35	CDRH2-34	CDRH3-51
  	65C1	CDRH1-35	CDRH2-52	CDRH3-58
  	64A7	CDRH1-40	CDRH2-51	CDRH3-57
  	66D4	CDRH1-43	CDRH2-56	CDRH3-61
  	65B1	CDRH1-44	CDRH2-57	CDRH3-62
  	67A4	CDRH1-45	CDRH2-58	CDRH3-63
  	65B4	CDRH1-46	CDRH2-59	CDRH3-64
  	63A10	CDRH1-38	CDRH2-60	CDRH3-56
  	65H11	CDRH1-38	CDRH2-61	CDRH3-56
  	64C8	CDRH1-12	CDRH2-62	CDRH3-65
  	65E3	CDRH1-47	CDRH2-63	CDRH3-66
  	65D4	CDRH1-48	CDRH2-22	CDRH3-67
  	65D1	CDRH1-49	CDRH2-64	CDRH3-68
  	67G8	CDRH1-12	CDRH2-65	CDRH3-69
  	65B7	CDRH1-50	CDRH2-52	CDRH3-70
  	64A6	CDRH1-14	CDRH2-66	CDRH3-71
  	65F9	CDRH1-36	CDRH2-34	CDRH3-72
  	67F5	CDRH1-24	CDRH2-67	CDRH3-53
  	64B10	CDRH1-36	CDRH2-68	CDRH3-73
  	68C8	CDRH1-51	CDRH2-69	CDRH3-74
  	67A5	CDRH1-25	CDRH2-31	CDRH3-75
  	67C10	CDRH1-25	CDRH2-31	CDRH3-76
  	64H6	CDRH1-25	CDRH2-70	CDRH3-77
  	63F9	CDRH1-52	CDRH2-71	CDRH3-78
  	67F6	CDRH1-53	CDRH2-31	CDRH3-79
  	48H11	CDRH1-4	CDRH2-4	CDRH3-4
  	52A8	CDRH1-15	CDRH2-17	CDRH3-17
  	52F8	CDRH1-17	CDRH2-20	CDRH3-21
  	49H12	CDRH1-10	CDRH2-10	CDRH3-10
  	54A1	CDRH1-10	CDRH2-25	CDRH3-10
  	55G9	CDRH1-10	CDRH2-25	CDRH3-10
  	49C8	CDRH1-7	CDRH2-7	CDRH3-7
  	52H1	CDRH1-7	CDRH2-7	CDRH3-7
  	60G5.2	CDRH1-33	CDRH2-42	CDRH3-48
  	49G3	CDRH1-9	CDRH2-9	CDRH3-9
  	59A10	CDRH1-30	CDRH2-37	CDRH3-41
  	49H4	CDRH1-30	CDRH2-37	CDRH3-41
  	48F8	CDRH1-3	CDRH2-3	CDRH3-3
  	53B9	CDRH1-3	CDRH2-3	CDRH3-3
  	56B4	CDRH1-3	CDRH2-3	CDRH3-3
  	57E7	CDRH1-3	CDRH2-3	CDRH3-3
  	57F11	CDRH1-3	CDRH2-3	CDRH3-3
  	59C9	CDRH1-31	CDRH2-38	CDRH3-42
  	58A5	CDRH1-31	CDRH2-38	CDRH3-42
  	57A4	CDRH1-31	CDRH2-38	CDRH3-42
  	57F9	CDRH1-31	CDRH2-38	CDRH3-42
  	51G2	CDRH1-3	CDRH2-16	CDRH3-16
  	56A7	CDRH1-3	CDRH2-16	CDRH3-32
  	56E4	CDRH1-3	CDRH2-16	CDRH3-32
  	54H10.1	CDRH1-21	CDRH2-26	CDRH3-27
  	55D1	CDRH1-21	CDRH2-26	CDRH3-27
  	48H3	CDRH1-21	CDRH2-26	CDRH3-27
  	53C11	CDRH1-21	CDRH2-26	CDRH3-27
  	59G10.3	CDRH1-32	CDRH2-40	CDRH3-45
  	51C10.1	CDRH1-13	CDRH2-13	CDRH3-13
  	59D10 v1	CDRH1-13	CDRH2-13	CDRH3-13
  	59D10 v2	CDRH1-13	CDRH2-13	CDRH3-13
  	60F9	CDRH1-21	CDRH2-41	CDRH3-47
  	48B4	CDRH1-21	CDRH2-41	CDRH3-47
  	52D6	CDRH1-21	CDRH2-41	CDRH3-47
  	61G5	CDRH1-21	CDRH2-43	CDRH3-49
  	59G10.2	CDRH1-6	CDRH2-39	CDRH3-44
  	51A8	CDRH1-12	CDRH2-12	CDRH3-12
  	53H5.2	CDRH1-12	CDRH2-23	CDRH3-24
  	53F6	CDRH1-19	CDRH2-22	CDRH3-23
  	56C11	CDRH1-12	CDRH2-30	CDRH3-33
  	49A10	CDRH1-6	CDRH2-6	CDRH3-6
  	48D4	CDRH1-6	CDRH2-6	CDRH3-6
  	49G2	CDRH1-8	CDRH2-8	CDRH3-8
  	50C12	CDRH1-8	CDRH2-8	CDRH3-8
  	55G11	CDRH1-8	CDRH2-8	CDRH3-8
  	52C1	CDRH1-12	CDRH2-19	CDRH3-19
  	55E9	CDRH1-23	CDRH2-28	CDRH3-30
  	60D7	CDRH1-12	CDRH2-22	CDRH3-46
  	51C10.2	CDRH1-14	CDRH2-14	CDRH3-14
  	55D3	CDRH1-22	CDRH2-27	CDRH3-28
  	57B12	CDRH1-28	CDRH2-34	CDRH3-28
  	52C5	CDRH1-2	CDRH2-1	CDRH3-20
  	60G5.1	CDRH1-2	CDRH2-1	CDRH3-20
  	55E4	CDRH1-2	CDRH2-1	CDRH3-20
  	49B11	CDRH1-2	CDRH2-1	CDRH3-20
  	50H10	CDRH1-2	CDRH2-1	CDRH3-20
  	53C1	CDRH1-2	CDRH2-1	CDRH3-20
  	56G1	CDRH1-2	CDRH2-1	CDRH3-20
  	48F3	CDRH1-2	CDRH2-2	CDRH3-2
  	48C9	CDRH1-1	CDRH2-1	CDRH3-1
  	49A12	CDRH1-1	CDRH2-1	CDRH3-1
  	51E2	CDRH1-1	CDRH2-1	CDRH3-1
  	51E5	CDRH1-2	CDRH2-15	CDRH3-15
  	53H5.3	CDRH1-20	CDRH2-24	CDRH3-25
  	56G3.3	CDRH1-27	CDRH2-33	CDRH3-37
  	55B10	CDRH1-27	CDRH2-33	CDRH3-37
  	52B8	CDRH1-16	CDRH2-18	CDRH3-18
  	55G5	CDRH1-24	CDRH2-29	CDRH3-31
  	52H2	CDRH1-18	CDRH2-21	CDRH3-22
  	56G3.2	CDRH1-26	CDRH2-32	CDRH3-36
  	56E7	CDRH1-25	CDRH2-31	CDRH3-34
  	57D9	CDRH1-29	CDRH2-35	CDRH3-39
  	48G4	CDRH1-5	CDRH2-5	CDRH3-5
  	53C3.1	CDRH1-5	CDRH2-5	CDRH3-5
  	50G1	CDRH1-11	CDRH2-11	CDRH3-11
  	58C2	CDRH1-6	CDRH2-36	CDRH3-40
  	63H11	CDRH1-35	CDRH2-34	CDRH3-51
  	61H5	CDRH1-27	CDRH2-72	CDRH3-37
  	52B9	CDRH1-27	CDRH2-72	CDRH3-37
  	54H10.3	CDRH1-43	CDRH2-74	CDRH3-81
  	50G5 v1	CDRH1-37	CDRH2-73	CDRH3-35
  	50G5 v2	CDRH1-37	CDRH2-73	CDRH3-35
  	51C1	CDRH1-2	CDRH2-1	CDRH3-20
  	53C3.2	CDRH1-39	CDRH2-77	CDRH3-43
  	50D4	CDRH1-41	CDRH2-75	CDRH3-80
  	55A7	CDRH1-24	CDRH2-18	CDRH3-38
  	55E6	CDRH1-3	CDRH2-76	CDRH3-29
  	61E1	CDRH1-42	CDRH2-35	CDRH3-26

• In an additional aspect, an antigen binding protein includes the following associations of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 presented for convenience in tablular form and in reference to the clone source of the association:

• TABLE 6
  CDRH and CDRL Associations

  Clone ID	CDRL1	CDRL2	CDRL3	CDRH1	CDRH2	CDRH3
  63G8	CDRL1-13	CDRL2-29	CDRL3-41	CDRH1-34	CDRH2-12	CDRH3-50
  64A8	CDRL1-13	CDRL2-29	CDRL3-41	CDRH1-34	CDRH2-12	CDRH3-50
  67B4	CDRL1-13	CDRL2-29	CDRL3-41	CDRH1-34	CDRH2-12	CDRH3-50
  68D3	CDRL1-13	CDRL2-29	CDRL3-41	CDRH1-34	CDRH2-12	CDRH3-50
  64E6	CDRL1-46	CDRL2-34	CDRL3-42	CDRH1-35	CDRH2-44	CDRH3-51
  65E8	CDRL1-46	CDRL2-34	CDRL3-42	CDRH1-35	CDRH2-44	CDRH3-51
  65F11	CDRL1-46	CDRL2-34	CDRL3-42	CDRH1-35	CDRH2-44	CDRH3-51
  67G7	CDRL1-46	CDRL2-34	CDRL3-42	CDRH1-35	CDRH2-44	CDRH3-51
  63B6	CDRL1-47	CDRL2-3	CDRL3-43	CDRH1-36	CDRH2-45	CDRH3-52
  64D4	CDRL1-47	CDRL2-3	CDRL3-43	CDRH1-36	CDRH2-45	CDRH3-52
  65C3	CDRL1-48	CDRL2-36	CDRL3-44	CDRH1-24	CDRH2-46	CDRH3-53
  68D5	CDRL1-48	CDRL2-36	CDRL3-44	CDRH1-24	CDRH2-46	CDRH3-53
  63E6	CDRL1-49	CDRL2-14	CDRL3-45	CDRH1-37	CDRH2-47	CDRH3-54
  66F7	CDRL1-50	CDRL2-14	CDRL3-45	CDRH1-37	CDRH2-47	CDRH3-54
  64H5	CDRL1-51	CDRL2-37	CDRL3-46	CDRH1-12	CDRH2-48	CDRH3-55
  65G4	CDRL1-51	CDRL2-37	CDRL3-46	CDRH1-12	CDRH2-48	CDRH3-55
  67G10v1	CDRL1-52	CDRL2-38	CDRL3-47	CDRH1-38	CDRH2-49	CDRH3-56
  67G10v2	CDRL1-53	CDRL2-39	CDRL3-48	CDRH1-38	CDRH2-49	CDRH3-56
  66B4	CDRL1-57	CDRL2-40	CDRL3-50	CDRH1-15	CDRH2-53	CDRH3-59
  66G2	CDRL1-22	CDRL2-41	CDRL3-51	CDRH1-12	CDRH2-54	CDRH3-50
  68G5	CDRL1-59	CDRL2-42	CDRL3-52	CDRH1-12	CDRH2-55	CDRH3-60
  63F5	CDRL1-54	CDRL2-20	CDRL3-42	CDRH1-35	CDRH2-50	CDRH3-51
  66F6	CDRL1-46	CDRL2-35	CDRL3-42	CDRH1-35	CDRH2-34	CDRH3-51
  65C1	CDRL1-56	CDRL2-35	CDRL3-42	CDRH1-35	CDRH2-52	CDRH3-58
  64A7	CDRL1-55	CDRL2-20	CDRL3-49	CDRH1-40	CDRH2-51	CDRH3-57
  66D4	CDRL1-60	CDRL2-14	CDRL3-53	CDRH1-43	CDRH2-56	CDRH3-61
  65B1	CDRL1-61	CDRL2-43	CDRL3-15	CDRH1-44	CDRH2-57	CDRH3-62
  67A4	CDRL1-62	CDRL2-25	CDRL3-55	CDRH1-45	CDRH2-58	CDRH3-63
  65B4	CDRL1-63	CDRL2-25	CDRL3-55	CDRH1-46	CDRH2-59	CDRH3-64
  63A10	CDRL1-52	CDRL2-45	CDRL3-56	CDRH1-38	CDRH2-60	CDRH3-56
  65H11	CDRL1-65	CDRL2-38	CDRL3-57	CDRH1-38	CDRH2-61	CDRH3-56
  64C8	CDRL1-66	CDRL2-47	CDRL3-58	CDRH1-12	CDRH2-62	CDRH3-65
  65E3	CDRL1-51	CDRL2-42	CDRL3-59	CDRH1-47	CDRH2-63	CDRH3-66
  65D4	CDRL1-67	CDRL2-42	CDRL3-60	CDRH1-48	CDRH2-22	CDRH3-67
  65D1	CDRL1-39	CDRL2-32	CDRL3-61	CDRH1-49	CDRH2-64	CDRH3-68
  67G8	CDRL1-69	CDRL2-37	CDRL3-59	CDRH1-12	CDRH2-65	CDRH3-69
  65B7	CDRL1-70	CDRL2-20	CDRL3-62	CDRH1-50	CDRH2-52	CDRH3-70
  64A6	CDRL1-71	CDRL2-48	CDRL3-63	CDRH1-14	CDRH2-66	CDRH3-71
  65F9	CDRL1-72	CDRL2-15	CDRL3-63	CDRH1-36	CDRH2-34	CDRH3-72
  67F5	CDRL1-72	CDRL2-49	CDRL3-64	CDRH1-24	CDRH2-67	CDRH3-53
  64B10	CDRL1-73	CDRL2-50	CDRL3-17	CDRH1-36	CDRH2-68	CDRH3-73
  68C8	CDRL1-74	CDRL2-16	CDRL3-17	CDRH1-51	CDRH2-69	CDRH3-74
  67A5	CDRL1-75	CDRL2-5	CDRL3-66	CDRH1-25	CDRH2-31	CDRH3-75
  67C10	CDRL1-75	CDRL2-5	CDRL3-5	CDRH1-25	CDRH2-31	CDRH3-76
  64H6	CDRL1-51	CDRL2-37	CDRL3-68	CDRH1-25	CDRH2-70	CDRH3-77
  63F9	CDRL1-76	CDRL2-51	CDRL3-69	CDRH1-52	CDRH2-71	CDRH3-78
  67F6	CDRL1-77	CDRL2-52	CDRL3-5	CDRH1-53	CDRH2-31	CDRH3-79
  48H11	CDRL1-4	CDRL2-4	CDRL3-4	CDRH1-4	CDRH2-4	CDRH3-4
  52A8	CDRL1-15	CDRL2-14	CDRL3-15	CDRH1-15	CDRH2-17	CDRH3-17
  52F8	CDRL1-19	CDRL2-17	CDRL3-19	CDRH1-17	CDRH2-20	CDRH3-21
  49H12	CDRL1-9	CDRL2-8	CDRL3-9	CDRH1-10	CDRH2-10	CDRH3-10
  54A1	CDRL1-24	CDRL2-6	CDRL3-9	CDRH1-10	CDRH2-25	CDRH3-10
  55G9	CDRL1-24	CDRL2-6	CDRL3-9	CDRH1-10	CDRH2-25	CDRH3-10
  49C8	CDRL1-6	CDRL2-6	CDRL3-6	CDRH1-7	CDRH2-7	CDRH3-7
  52H1	CDRL1-6	CDRL2-6	CDRL3-6	CDRH1-7	CDRH2-7	CDRH3-7
  60G5.2	CDRL1-44	CDRL2-32	CDRL3-40	CDRH1-33	CDRH2-42	CDRH3-48
  49G3	CDRL1-8	CDRL2-7	CDRL3-8	CDRH1-9	CDRH2-9	CDRH3-9
  59A10	CDRL1-14	CDRL2-28	CDRL3-14	CDRH1-30	CDRH2-37	CDRH3-41
  49H4	CDRL1-14	CDRL2-28	CDRL3-14	CDRH1-30	CDRH2-37	CDRH3-41
  48F8	CDRL1-3	CDRL2-3	CDRL3-3	CDRH1-3	CDRH2-3	CDRH3-3
  53B9	CDRL1-3	CDRL2-3	CDRL3-3	CDRH1-3	CDRH2-3	CDRH3-3
  56B4	CDRL1-3	CDRL2-3	CDRL3-3	CDRH1-3	CDRH2-3	CDRH3-3
  57E7	CDRL1-3	CDRL2-3	CDRL3-3	CDRH1-3	CDRH2-3	CDRH3-3
  57F11	CDRL1-3	CDRL2-3	CDRL3-3	CDRH1-3	CDRH2-3	CDRH3-3
  59C9	CDRL1-37	CDRL2-29	CDRL3-14	CDRH1-31	CDRH2-38	CDRH3-42
  58A5	CDRL1-37	CDRL2-29	CDRL3-14	CDRH1-31	CDRH2-38	CDRH3-42
  57A4	CDRL1-37	CDRL2-29	CDRL3-14	CDRH1-31	CDRH2-38	CDRH3-42
  57F9	CDRL1-37	CDRL2-29	CDRL3-14	CDRH1-31	CDRH2-38	CDRH3-42
  51G2	CDRL1-14	CDRL2-13	CDRL3-14	CDRH1-3	CDRH2-16	CDRH3-16
  56A7	CDRL1-29	CDRL2-24	CDRL3-14	CDRH1-3	CDRH2-16	CDRH3-32
  56E4	CDRL1-29	CDRL2-24	CDRL3-14	CDRH1-3	CDRH2-16	CDRH3-32
  54H10.1	CDRL1-25	CDRL2-20	CDRL3-24	CDRH1-21	CDRH2-26	CDRH3-27
  55D1	CDRL1-25	CDRL2-20	CDRL3-24	CDRH1-21	CDRH2-26	CDRH3-27
  48H3	CDRL1-25	CDRL2-20	CDRL3-24	CDRH1-21	CDRH2-26	CDRH3-27
  53C11	CDRL1-25	CDRL2-20	CDRL3-24	CDRH1-21	CDRH2-26	CDRH3-27
  59G10.3	CDRL1-41	CDRL2-16	CDRL3-37	CDRH1-32	CDRH2-40	CDRH3-45
  51C10.1	CDRL1-12	CDRL2-10	CDRL3-11	CDRH1-13	CDRH2-13	CDRH3-13
  59D10v1	CDRL1-38	CDRL2-10	CDRL3-34	CDRH1-13	CDRH2-13	CDRH3-13
  59D10v2	CDRL1-39	CDRL2-30	CDRL3-35	CDRH1-13	CDRH2-13	CDRH3-13
  60F9	CDRL1-43	CDRL2-31	CDRL3-39	CDRH1-21	CDRH2-41	CDRH3-47
  48B4	CDRL1-43	CDRL2-31	CDRL3-39	CDRH1-21	CDRH2-41	CDRH3-47
  52D6	CDRL1-43	CDRL2-31	CDRL3-39	CDRH1-21	CDRH2-41	CDRH3-47
  61G5	CDRL1-45	CDRL2-33	CDRL3-39	CDRH1-21	CDRH2-43	CDRH3-49
  59G10.2	CDRL1-40	CDRL2-11	CDRL3-36	CDRH1-6	CDRH2-39	CDRH3-44
  51A8	CDRL1-10	CDRL2-9	CDRL3-10	CDRH1-12	CDRH2-12	CDRH3-12
  53H5.2	CDRL1-22	CDRL2-14	CDRL3-22	CDRH1-12	CDRH2-23	CDRH3-24
  53F6	CDRL1-21	CDRL2-19	CDRL3-21	CDRH1-19	CDRH2-22	CDRH3-23
  56C11	CDRL1-30	CDRL2-25	CDRL3-28	CDRH1-12	CDRH2-30	CDRH3-33
  49A10	CDRL1-5	CDRL2-5	CDRL3-5	CDRH1-6	CDRH2-6	CDRH3-6
  48D4	CDRL1-5	CDRL2-5	CDRL3-5	CDRH1-6	CDRH2-6	CDRH3-6
  49G2	CDRL1-7	CDRL2-5	CDRL3-7	CDRH1-8	CDRH2-8	CDRH3-8
  50C12	CDRL1-7	CDRL2-5	CDRL3-7	CDRH1-8	CDRH2-8	CDRH3-8
  55G11	CDRL1-7	CDRL2-5	CDRL3-7	CDRH1-8	CDRH2-8	CDRH3-8
  52C1	CDRL1-17	CDRL2-16	CDRL3-17	CDRH1-12	CDRH2-19	CDRH3-19
  55E9	CDRL1-27	CDRL2-17	CDRL3-26	CDRH1-23	CDRH2-28	CDRH3-30
  60D7	CDRL1-1	CDRL2-5	CDRL3-38	CDRH1-12	CDRH2-22	CDRH3-46
  51C10.2	CDRL1-12	CDRL2-11	CDRL3-12	CDRH1-14	CDRH2-14	CDRH3-14
  55D3	CDRL1-26	CDRL2-14	CDRL3-25	CDRH1-22	CDRH2-27	CDRH3-28
  57B12	CDRL1-34	CDRL2-14	CDRL3-32	CDRH1-28	CDRH2-34	CDRH3-28
  52C5	CDRL1-18	CDRL2-14	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  60G5.1	CDRL1-18	CDRL2-14	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  55E4	CDRL1-18	CDRL2-21	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  49B11	CDRL1-18	CDRL2-21	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  50H10	CDRL1-18	CDRL2-21	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  53C1	CDRL1-18	CDRL2-21	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  56G1	CDRL1-18	CDRL2-14	CDRL3-30	CDRH1-2	CDRH2-1	CDRH3-20
  48F3	CDRL1-2	CDRL2-2	CDRL3-2	CDRH1-2	CDRH2-2	CDRH3-2
  48C9	CDRL1-1	CDRL2-1	CDRL3-1	CDRH1-1	CDRH2-1	CDRH3-1
  49A12	CDRL1-1	CDRL2-1	CDRL3-1	CDRH1-1	CDRH2-1	CDRH3-1
  51E2	CDRL1-1	CDRL2-1	CDRL3-1	CDRH1-1	CDRH2-1	CDRH3-1
  51E5	CDRL1-13	CDRL2-12	CDRL3-13	CDRH1-2	CDRH2-15	CDRH3-15
  53H5.3	CDRL1-23	CDRL2-15	CDRL3-23	CDRH1-20	CDRH2-24	CDRH3-25
  56G3.3	CDRL1-33	CDRL2-27	CDRL3-31	CDRH1-27	CDRH2-33	CDRH3-37
  55B10	CDRL1-33	CDRL2-27	CDRL3-31	CDRH1-27	CDRH2-33	CDRH3-37
  52B8	CDRL1-16	CDRL2-15	CDRL3-16	CDRH1-16	CDRH2-18	CDRH3-18
  55G5	CDRL1-28	CDRL2-23	CDRL3-27	CDRH1-24	CDRH2-29	CDRH3-31
  52H2	CDRL1-20	CDRL2-18	CDRL3-20	CDRH1-18	CDRH2-21	CDRH3-22
  56G3.2	CDRL1-32	CDRL2-26	CDRL3-16	CDRH1-26	CDRH2-32	CDRH3-36
  56E7	CDRL1-31	CDRL2-7	CDRL3-29	CDRH1-25	CDRH2-31	CDRH3-34
  57D9	CDRL1-35	CDRL2-20	CDRL3-33	CDRH1-29	CDRH2-35	CDRH3-39
  61H5	CDRL1-33	CDRL2-20	CDRL3-31	CDRH1-27	CDRH2-72	CDRH3-37
  52B9	CDRL1-33	CDRL2-20	CDRL3-31	CDRH1-27	CDRH2-72	CDRH3-37
  48G4	CDRL1-79	CDRL2-35	CDRL3-71	CDRH1-5	CDRH2-5	CDRH3-5
  53C3.1	CDRL1-79	CDRL2-35	CDRL3-71	CDRH1-5	CDRH2-5	CDRH3-5
  50G1	CDRL1-7	CDRL2-5	CDRL3-38	CDRH1-11	CDRH2-11	CDRH3-11
  58C2	CDRL1-81	CDRL2-5	CDRL3-66	CDRH1-6	CDRH2-36	CDRH3-40
  54H10.3	CDRL1-42	CDRL2-46	CDRL3-53	CDRH1-43	CDRH2-74	CDRH3-81
  50G5v1	CDRL1-22	CDRL2-14	CDRL3-72	CDRH1-37	CDRH2-73	CDRH3-35
  50G5v2	CDRL1-78	CDRL2-22	CDRL3-75	CDRH1-37	CDRH2-73	CDRH3-35
  51C1	CDRL1-18	CDRL2-14	CDRL3-18	CDRH1-2	CDRH2-1	CDRH3-20
  53C3.2	CDRL1-36	CDRL2-44	CDRL3-70	CDRH1-39	CDRH2-77	CDRH3-43
  50D4	CDRL1-26	CDRL2-53	CDRL3-74	CDRH1-41	CDRH2-75	CDRH3-80
  55A7	CDRL1-58	CDRL2-14	CDRL3-54	CDRH1-24	CDRH2-18	CDRH3-38
  55E6	CDRL1-64	CDRL2-20	CDRL3-65	CDRH1-3	CDRH2-76	CDRH3-29
  61E1	CDRL1-68	CDRL2-14	CDRL3-67	CDRH1-42	CDRH2-35	CDRH3-26
  63H11	CDRL1-46	CDRL2-34	CDRL3-42	CDRH1-35	CDRH2-34	CDRH3-51

Consensus Sequences
• In yet another aspect, the CDRs disclosed herein include consensus sequences derived from groups of related monoclonal antibodies. As described herein, a “consensus sequence” refers to amino acid sequences having conserved amino acids common among a number of sequences and variable amino acids that vary within a given amino acid sequences. The CDR consensus sequences provided include CDRs corresponding to each of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3.
• Consensus sequences were determined using standard analyses of the CDRs corresponding to the V_H and V_L of the disclosed antigen binding proteins shown in Tables 3A and 3B, some of which specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. The consensus sequences can be determined by keeping the CDRs contiguous within the same sequence corresponding to a V_H or V_L.
Light Chain CDR3

• Group 1

  (SEQ ID NO: 1439)

  QQFGSSLT

  Group 2

  (SEQ ID NO: 1440)

  QQS Y S T S LT

  (SEQ ID NO: 1441)

  QQS Y S S P LT

  (SEQ ID NO: 1442)

  QQS F S T P LT

  (SEQ ID NO: 1443)

  QQS X 1 S X 2 X 3 LT

  wherein X1 is Y or F; X2 is T or S; and X3

  is P or S.

  Group 3

  (SEQ ID NO: 1444)

  LQ R N SYP L T

  (SEQ ID NO: 1445)

  LQ H N SYP R T

  (SEQ ID NO: 1446)

  LQ H S SYP L T

  (SEQ ID NO: 1447)

  LQ X 4 X 5 SYP X 6 T

  wherein X4 is H or R; X5 is N or S; and X6

  is L or R.

  Group 4

  (SEQ ID NO: 1448)

  MQR I EFP L T

  (SEQ ID NO: 1449)

  MQR I EFP I T

  (SEQ ID NO: 1450)

  MQR L EFP I T

  (SEQ ID NO: 1451)

  MQR X 7 EFP X 8 T

  wherein X7 is I or L; and X8 us I or L.

  Group 5

  (SEQ ID NO: 1452)

  Q V WDS N P VV

  (SEQ ID NO: 1453)

  Q L WDS S T VV

  (SEQ ID NO: 1454)

  Q V WDS S S VV

  (SEQ ID NO: 1455)

  Q V WDS S P VV

  (SEQ ID NO: 1456)

  Q V WDS S T VV

  (SEQ ID NO: 1457)

  Q X 9 WDS X 10 X 11 VV

  wherein X9 is V or L; X10 is S or N; and X11

  is T, P or S.

  Group 6

  (SEQ ID NO: 1458)

  QQYN N WP L T

  (SEQ ID NO: 1459)

  QQYN N WP W T

  (SEQ ID NO: 1460)

  QQYN T WP W T

  (SEQ ID NO: 1461)

  QQYN X 12 WP X 13 T

  wherein X12 is N or T; and X13 is W or L.

  Group 7

  (SEQ ID NO: 1462)

  QVWDSS S D H V V

  (SEQ ID NO: 1463)

  QVWDSS S D V V

  (SEQ ID NO: 1464)

  QVWDSS C D G V

  (SEQ ID NO: 1465)

  QVWDSS S D G V

  (SEQ ID NO: 1466)

  QVWDSS X 14 D X 15 V X 16

  wherein X14 is S or C; X15 is H, V or G; and

  X16 is V or absent.

  Group 8

  (SEQ ID NO: 1467)

  QQSS S IPWT

  (SEQ ID NO: 1468)

  QQSS T IPWT

  (SEQ ID NO: 1469)

  QQSS X 17 IPWT

  wherein X17 is S or T.

  Group 9

  (SEQ ID NO: 1470)

  QQTNSFPPWT

  Group 10

  (SEQ ID NO: 1471)

  GTWDSSLS A V V

  (SEQ ID NO: 1472)

  GTWDSSLS V V V

  (SEQ ID NO: 1473)

  GTWDSSLS A M V

  (SEQ ID NO: 1474)

  GTWDSSLS X 18 X 19 V

  wherein X18 is A or V; and X19 is V or M.

  Group 11

  (SEQ ID NO: 1475)

  QQYDNLP L T

  (SEQ ID NO: 1476)

  QQYDNLP F T

  (SEQ ID NO: 1477)

  QQYDNLP X 20 T

  wherein X20 is L or F.

  Group 12

  (SEQ ID NO: 1478)

  QQYGSS P PWT

  (SEQ ID NO: 1479)

  QQYGSS PWT

  (SEQ ID NO: 1480)

  QQYGSS X 21 PWT

  wherein X21 is P or absent.

  Group 13

  (SEQ ID NO: 1481)

  QQYG R S L FT

  (SEQ ID NO: 1482)

  QQYG T S P FT

  (SEQ ID NO: 1483)

  QQYG X 22 S X 23 FT

  wherein X22 is R or T; and X23 is L or P.

  Group 14

  (SEQ ID NO: 1484)

  QQYGSS R S

  (SEQ ID NO: 1485)

  QQYGSS P R S

  (SEQ ID NO: 1486)

  QQYGSS R T

  (SEQ ID NO: 1487)

  QQYGSS C S

  (SEQ ID NO: 1488)

  QQYGSS X 24 X 25 X 26

  wherein X24 is P or absent; X25 is R or C and

  X26 is S or T.

  Group 15

  (SEQ ID NO: 1489)

  QADWSS T T W V

  (SEQ ID NO: 1490)

  QADWSS T A V

  (SEQ ID NO: 1491)

  QADWSS T W V

  (SEQ ID NO: 1492)

  QAWDSS X 27 T X 28 V

  wherein X27 is T or absent; and X28 is W or A.

  Group 16

  (SEQ ID NO: 1493)

  QADWS G TV V

  (SEQ ID NO: 1494)

  QADWS T TV V

  (SEQ ID NO: 1495)

  QAWDS A TV I

  (SEQ ID NO: 1496)

  QAWDS X 29 TV X 30

  wherein X29 is G, T, A or absent; and X30

  is V or I.

  Group 17

  (SEQ ID NO: 1497)

  QQ S YSA T FT

  (SEQ ID NO: 1498)

  QQ T YSA P FT

  (SEQ ID NO: 1499)

  QQ X 31 YSA X 32 FT

  wherein X31 is S or T; and X32 is T or P.

  Group 18

  (SEQ ID NO: 1500)

  QQYN I YPRT

  (SEQ ID NO: 1501)

  QQYN T YPRT

  (SEQ ID NO: 1502)

  QQYN X 33 YPRT

  wherein X33 is I or T.

  Group 19

  (SEQ ID NO: 1503)

  HQ S S DLPLT

  (SEQ ID NO: 1504)

  HQ Y D DLPLT

  (SEQ ID NO: 1505)

  HQ X 34 X 35 DLPLT

  wherein X34 is S or Y; and X35 is S or D.

  Group 20

  (SEQ ID NO: 1506)

  MQALQT P F T

  (SEQ ID NO: 1507)

  MQALQT L I T

  (SEQ ID NO: 1508)

  MQALQT X 36 X 37 T

  wherein X36 is P or L; and X37 is F or I.

  Group 21

  (SEQ ID NO: 1509)

  QQFGRSFT

  Group 22

  (SEQ ID NO: 1510)

  YSTDSS V NHVV

  (SEQ ID NO: 1511)

  YSTDSS G NHVV

  (SEQ ID NO: 1512)

  YSTDSS X 38 NHVV

  wherein X38 is V or G.

Light Chain CDR2

• Group 1

  (SEQ ID NO: 1513)

  	A ASSL Q S

  (SEQ ID NO: 1514)

  	S ASSL Q S

  (SEQ ID NO: 1515)

  	A ASSL Q F

  (SEQ ID NO: 1516)

  	A ASSL K S

  (SEQ ID NO: 1517)

  	X 39 ASSL X 40 X 41
  	wherein X39 is A or S; X40 is Q or K;
  	and X41 is S or F.
  	Group 2

  (SEQ ID NO: 1518)

  	G A S S R A T

  (SEQ ID NO: 1519)

  	G A S S R D T

  (SEQ ID NO: 1520)

  	G T S T R A T

  (SEQ ID NO: 1521)

  	G A S T R A T

  (SEQ ID NO: 1522)

  	G A S A R A T

  (SEQ ID NO: 1523)

  	G A S R R A T

  (SEQ ID NO: 1524)

  	G A S N R A T

  (SEQ ID NO: 1525)

  	G X 42 S X 43 R X 44 T
  	wherein X42 is A or T; X43 is S, T, A, R or N;
  	and X44 is A or D.
  	Group 3

  (SEQ ID NO: 1526)

  	GAFSRA S

  (SEQ ID NO: 1527)

  	GAFSRA T

  (SEQ ID NO: 1528)

  	GAFSRA X 45
  	wherein X45 is S or T.
  	Group 4

  (SEQ ID NO: 1529)

  	Q D T KRPS

  (SEQ ID NO: 1530)

  	R D S KRPS

  (SEQ ID NO: 1531)

  	E D S KRPS

  (SEQ ID NO: 1532)

  	Q D S KRPS

  (SEQ ID NO: 1533)

  	X 46 D X 47 KRPS
  	wherein X46 is Q, R or E; and X47 is T or S.
  	Group 5

  (SEQ ID NO: 1534)

  	TLS Y RAS

  (SEQ ID NO: 1535)

  	TLS F RAS

  (SEQ ID NO: 1536)

  	TLS X 48 RAS
  	wherein X48 is Y or F.
  	Group 6

  (SEQ ID NO: 1537)

  	AASNLQ R

  (SEQ ID NO: 1538)

  	AASNLQ S

  (SEQ ID NO: 1539)

  	AASNLQ X 49
  	wherein X49 is R or S.
  	Group 7

  (SEQ ID NO: 1540)

  	G A SNRA I

  (SEQ ID NO: 1541)

  	G S SNRA I

  (SEQ ID NO: 1542)

  	G S SNRA T

  (SEQ ID NO: 1543)

  	G X 50 SNRA X 51
  	wherein X50 is A or S; and X51 is I or T.
  	Group 8

  (SEQ ID NO: 1544)

  	D A S S LQS

  (SEQ ID NO: 1545)

  	D A S T LQS

  (SEQ ID NO: 1546)

  	G A S S LQS

  (SEQ ID NO: 1547)

  	G A S N LQS

  (SEQ ID NO: 1548)

  	X 52 A S X 53 LQS
  	wherein X52 is D or G; and X53 is S, T or N.
  	Group 9

  (SEQ ID NO: 1549)

  	DN N KRPS

  (SEQ ID NO: 1550)

  	DN D KRPS

  (SEQ ID NO: 1551)

  	DN X 53 KRPS
  	wherein X53 is N or D.
  	Group 10

  (SEQ ID NO: 1552)

  	D A SNLET

  (SEQ ID NO: 1553)

  	D V SNLET

  (SEQ ID NO: 1554)

  	D X 54 SNLET
  	wherein X54 is A or V.
  	Group 11

  (SEQ ID NO: 1555)

  	L G SNRAS

  (SEQ ID NO: 1556)

  	L D SNRAS

  (SEQ ID NO: 1557)

  	L X 55 SNRAS
  	wherein X55 is G or D.
  	Group 12

  (SEQ ID NO: 1558)

  	Q D N K RPS

  (SEQ ID NO: 1559)

  	Q N N K RPS

  (SEQ ID NO: 1560)

  	Q D N E RPS

  (SEQ ID NO: 1561)

  	Q X 56 N X 57 RPS
  	wherein X56 is D or N; and X57 is K or E.
  	Group 13

  (SEQ ID NO: 1562)

  	RDRNRPS
  	Group 14

  (SEQ ID NO: 1563)

  	S DSNRPS

  (SEQ ID NO: 1564)

  	C DSNRPS

  (SEQ ID NO: 1565)

  	X 58 DSNRPS
  	wherein X58 is S or C.
  	Group 15

  (SEQ ID NO: 1566)

  	DDSDRPS
  	Group 16

  (SEQ ID NO: 1567)

  	A V SSLQS

  (SEQ ID NO: 1568)

  	A S SSLQS

  (SEQ ID NO: 1569)

  	A X 59 SSLQS
  	wherein X59 is S or V.
  	Group 17

  (SEQ ID NO: 1570)

  	T A SSLQS

  (SEQ ID NO: 1571)

  	T T SSLQS

  (SEQ ID NO: 1572)

  	T X 60 SSLQS
  	wherein X60 is A or T.
  	Group 18

  (SEQ ID NO: 1573)

  	K V SNWDS

  (SEQ ID NO: 1574)

  	K G SNWDS

  (SEQ ID NO: 1575)

  	K X 61 SNWDS
  	wherein X61 is V or G.

Light Chain CDR1

• Group 1

  (SEQ ID NO: 1576)

  RAS Q S V S D I L A

  (SEQ ID NO: 1577)

  RAS P S V S S S Y L A

  (SEQ ID NO: 1578)

  RAS Q S F S S S Y L A

  (SEQ ID NO: 1579)

  RAS Q S V S R S H L A

  (SEQ ID NO: 1580)

  RAS Q S V S R D Y L A

  (SEQ ID NO: 1581)

  RAS Q S V S R N Y L A

  (SEQ ID NO: 1582)

  RAS Q S V S S M Y L A

  (SEQ ID NO: 1583)

  RAS Q S V S S Q L A

  (SEQ ID NO: 1584)

  RAS Q S I S S N L A

  (SEQ ID NO: 1585)

  RAS Q S V S S N L A

  (SEQ ID NO: 1586)

  RAS Q S V S S N V A

  (SEQ ID NO: 1587)

  RAS Q S V N S N L A

  (SEQ ID NO: 1588)

  RAS Q S V R S S S L A

  (SEQ ID NO: 1589)

  RAS Q S V S N S S L A

  (SEQ ID NO: 1590)

  RAS Q S V R N S S L A

  (SEQ ID NO: 1591)

  RAS X 62 S X 63 X 64 X 65 X 66 X 67 X 68 A

  wherein X62 is P or Q; X63 is V, I or F; X64 is S,

  R or absent; X65 is S, R or N; X66 is D, S, N or

  M; X67 is I, Y, H, Q, N or S; and X68 is L or V.

  Group 2

  (SEQ ID NO: 1592)

  R A SQ I I S R YLN

  (SEQ ID NO: 1593)

  R T SQ S I S S YLN

  (SEQ ID NO: 1594)

  R A SQ S I S N YLN

  (SEQ ID NO: 1595)

  R T SQ S I S S YLN

  (SEQ ID NO: 1596)

  R A SQ T I S I YLN

  (SEQ ID NO: 1597)

  R A SQ R I S S YLN

  (SEQ ID NO: 1598)

  R A SQ S I S S YLN

  (SEQ ID NO: 1599)

  R A SQ N I R T YLN

  (SEQ ID NO: 1600)

  R A SQ N I R S YLN

  (SEQ ID NO: 1601)

  R A SQ N I N N YLN

  (SEQ ID NO: 1602)

  R X 69 SQ X 70 I X 71 X 72 YLN

  wherein X69 is A or T; X70 is I, S, T or N;

  X71 is R, S or N; and X72 is R, S, N, or I.

  Group 3

  (SEQ ID NO: 1603)

  GGN N IGS Y N V H

  (SEQ ID NO: 1604)

  GGN N IGS I N V H

  (SEQ ID NO: 1605)

  GGN N IGS K S V Q

  (SEQ ID NO: 1606)

  GGN D IGS K S V H

  (SEQ ID NO: 1607)

  GGN N IGS K S V H

  (SEQ ID NO: 1608)

  GGN N IGS K T V H

  (SEQ ID NO: 1609)

  GGN N IGS K A V H

  (SEQ ID NO: 1610)

  GGN N IGS K N V H

  (SEQ ID NO: 1611)

  GGN D IGS K N V H

  (SEQ ID NO: 1612)

  GGN X 73 IGS X 74 X 75 V X 76

  wherein X73 is N, or D; X74 is Y, I or K;

  X75 is N, S, T or A; and X76 is H or Q.

  Group 4

  (SEQ ID NO: 1613)

  RASQ D IRNDL G

  (SEQ ID NO: 1614)

  RASQ D IRNDL A

  (SEQ ID NO: 1615)

  RASQ G IRNDL G

  (SEQ ID NO: 1616)

  RASQ X 77 IRNDL X 78

  wherein X77 is D or G; and X78 is G or A.

  Group 5

  (SEQ ID NO: 1617)

  RSSQSL L N S D A G T TYLD

  (SEQ ID NO: 1618)

  RSSQSL F D N D D G D TYLD

  (SEQ ID NO: 1619)

  RSSQSL L N S D D G N TYLD

  (SEQ ID NO: 1620)

  RSSQSL L D S D D G D TYLD

  (SEQ ID NO: 1621)

  RSSQSL L D S D D G N TYLD

  (SEQ ID NO: 1622)

  RSSQSL X 79 X 80 X 81 D X 82 G X 83 TYLD

  wherein X79 is L or F; X80 is N or D;

  X81 is S or N; X82 is A or D; and

  X83 is T, D or N.

  Group 6

  (SEQ ID NO: 1623)

  SG N K LGDKY V C

  (SEQ ID NO: 1624)

  SG D K LGDKY V C

  (SEQ ID NO: 1625)

  SG D K LGDKY A C

  (SEQ ID NO: 1626)

  SG D E LGDKY A C

  (SEQ ID NO: 1627)

  SG D N LGDKY A F

  (SEQ ID NO: 1628)

  SG D N LGDKY A C

  (SEQ ID NO: 1629)

  SG X 84 X 85 LGDKY X 86 X 87

  wherein X84 is N or D; X85 is K, E or N;

  X86 is V or A; and X87 is C or F.

  Group 7

  (SEQ ID NO: 1630)

  QASQ G I S N Y LN

  (SEQ ID NO: 1631)

  QASQ D I K K F LN

  (SEQ ID NO: 1632)

  QASQ D I N I Y LN

  (SEQ ID NO: 1633)

  QASQ D I S I Y LN

  (SEQ ID NO: 1634)

  QASQ D I T K Y LN

  (SEQ ID NO: 1635)

  QASQ X 88 I X 89 X 90 X 91 LN

  wherein X88 is G or D; X89 is S, K N or T;

  X90 is N, K or I; and X91 is Y or F.

  Group 8

  (SEQ ID NO: 1636)

  RASQ D I D S WL V

  (SEQ ID NO: 1637)

  RASQ G I S R WL A

  (SEQ ID NO: 1638)

  RASQ D I S S WL A

  (SEQ ID NO: 1639)

  RASQ G I S S WL A

  (SEQ ID NO: 1640)

  RASQ X 92 I X 93 X 94 WL X 95

  wherein X92 is D or G; X93 is D or S;

  X94 is R or S; and X95 is V or A.

  Group 9

  (SEQ ID NO: 1641)

  SGSSSNIG N NYV A

  (SEQ ID NO: 1642)

  SGSSSNIG I NYV S

  (SEQ ID NO: 1643)

  SGSSSNIG D NYV S

  (SEQ ID NO: 1644)

  SGSSSNIG N NYV S

  (SEQ ID NO: 1645)

  SGSSSNIG X 96 NYV X 97

  wherein X96 is N, I or D; and X97 is A or S.

  Group 10

  (SEQ ID NO: 1646)

  RAS Q DISNYLA

  (SEQ ID NO: 1647)

  RAS H DISNYLA

  (SEQ ID NO: 1648)

  RAS X 98 DISNYLA

  wherein X98 is Q or H.

  Group 11

  (SEQ ID NO: 1649)

  RASQ R V P SSY I V

  (SEQ ID NO: 1650)

  RASQ R V P SSY L V

  (SEQ ID NO: 1651)

  RASQ S V A SSY L V

  (SEQ ID NO: 1652)

  RASQ X 99 V X 100 SSY X 101 V

  wherein X99 is R or S; X100 is P or A; and

  X101 is I or L.

  Group 12

  (SEQ ID NO: 1653)

  RSSQSL L HSNG Y NYLD

  (SEQ ID NO: 1654)

  RSSQSL L HSNG F NYLD

  (SEQ ID NO: 1655)

  RSSQSL Q HSNG Y NYLD

  (SEQ ID NO: 1656)

  RSSQSL X 102 HSNG X 103 NYLD

  wherein X102 is L or Q; and X103 is Y or F.

  Group 13

  (SEQ ID NO: 1657)

  RASQT V RN N YLA

  (SEQ ID NO: 1658)

  RASQT I RN S YLA

  (SEQ ID NO: 1659)

  RASQT X 104 RN X 105 YLA

  wherein X104 is V or I; and X105 is N or S.

  Group 14

  (SEQ ID NO: 1660)

  RSS Q R LVYSDGNTYLN

  (SEQ ID NO: 1661)

  RSS P S LVYSDGNTYLN

  (SEQ ID NO: 1662)

  RSS X 106 X 107 LVYSDGNTYLN

  wherein X106 is Q or P; and X107 is R or S.

  Group 15

  (SEQ ID NO: 1663)

  SGDA L PKKYA Y

  (SEQ ID NO: 1664)

  SGDA V PKKYA N

  (SEQ ID NO: 1665)

  SGDA X 108 PKKYA X 109

  wherein X108 is L or V; and X109 is Y or N.

Heavy Chain CDR3

• Group 1

  (SEQ ID NO: 1666)

  MT T PYWYF D L

  (SEQ ID NO: 1667)

  MT S PYWYF D L

  (SEQ ID NO: 1668)

  MT T PYWYF G L

  (SEQ ID NO: 1669)

  MT X 110 PYWYF X 111 L

  wherein X110 is T or S; and X111 is D or G.

  Group 2

  (SEQ ID NO: 1670)

  D R Y Y DFW S GYP Y F R YYG L DV

  (SEQ ID NO: 1671)

  D Q Y F DFW S GYP F F Y YYG M DV

  (SEQ ID NO: 1672)

  D Q D Y DFW S GYP Y F Y YYG M DV

  (SEQ ID NO: 1673)

  D Q N Y DFW N GYP Y Y F YYG M DV

  (SEQ ID NO: 1674)

  D Q Y Y DFW S GYP Y Y H YYG M DV

  (SEQ ID NO: 1675)

  D X 112 X 113 X 114 DFW X 115 GYP X 116 X 117 X 118

  YYG X 119 DV

  wherein X112 is R or Q; X113 is Y, D or N; X114 is

  Y or F; X115 is S or N; X116 is Y or F; X117 is

  F or Y; X118 is R, Y, F or H; and X119 is L or M.

  Group 3

  (SEQ ID NO: 1676)

  VTGTDAFDF

  Group 4

  (SEQ ID NO: 1677)

  TVTKEDYYYYGMDV

  Group 5

  (SEQ ID NO: 1678)

  DSSGSYYVEDYFDY

  Group 6

  (SEQ ID NO: 1679)

  D W S IAVAG T FDY

  (SEQ ID NO: 1680)

  D L R IAVAG S FDY

  (SEQ ID NO: 1681)

  D X 119 X 120 IAVAG X 121 FDY

  wherein X119 is W or L; X120 is S or R; and

  X121 is T or S.

  Group 7

  (SEQ ID NO: 1682)

  EYYYGSGSYYP

  Group 8

  (SEQ ID NO: 1683)

  ELGDYPFFDY

  Group 9

  (SEQ ID NO: 1684)

  EYVAEAGFDY

  Group 10

  (SEQ ID NO: 1685)

  VAAVYWYFDL

  Group 11

  (SEQ ID NO: 1686)

  YNWNYGAFDF

  Group 12

  (SEQ ID NO: 1687)

  RASRGYR F GLAFAI

  (SEQ ID NO: 1688)

  RASRGYR Y GLAFAI

  (SEQ ID NO: 1689)

  RASRGYR X 122 GLAFAI

  wherein X122 is F or Y.

  Group 13

  (SEQ ID NO: 1690)

  DGITMVRGVTHYYGMDV

  Group 14

  (SEQ ID NO: 1691)

  DH S SGWYYYGMDV

  (SEQ ID NO: 1692)

  DH T SCWYYYGMDV

  (SEQ ID NO: 1693)

  DH X 123 SCWYYYGMDV

  wherein X123 is S or T.

  Group 15

  (SEQ ID NO: 1694)

  Y S T WDYYYG V DV

  (SEQ ID NO: 1695)

  Y R D WDYYYG M DV

  (SEQ ID NO: 1696)

  Y X 124 X 125 WDYYYG X 126 DV

  wherein X124 is S or R; X125 is T or D; and

  X126 is V or M.

  Group 16

  (SEQ ID NO: 1697)

  VLHY S DS R GYSYY S D F

  (SEQ ID NO: 1698)

  VLHY Y DS S GYSYY F D Y

  (SEQ ID NO: 1699)

  VLHY X 127 DS X 128 GYSYY X 129 D X 130

  wherein X127 is S or Y; X128 is R or S; X129 is S

  or F; and X130 is F or Y.

Heavy Chain CDR2

• Group 1

  (SEQ ID NO: 1700)

  N I Y Y S G T T Y F NPSLKS

  (SEQ ID NO: 1701)

  F I Y Y S G G T N Y NPSLKS

  (SEQ ID NO: 1702)

  Y I Y Y S G G T H Y NPSLKS

  (SEQ ID NO: 1703)

  Y I Y H S G S A Y Y NPSLKS

  (SEQ ID NO: 1704)

  Y I Y D S G S T Y Y NPSLKS

  (SEQ ID NO: 1705)

  S I Y Y S G T T Y Y NPSLKS

  (SEQ ID NO: 1706)

  M I Y Y S G T T Y Y NPSLKS

  (SEQ ID NO: 1707)

  Y I Y Y S G T T Y Y NPSLKS

  (SEQ ID NO: 1708)

  Y I Y Y S G S A Y Y NPSLKS

  (SEQ ID NO: 1709)

  Y I F Y S G S T Y Y NPSLKS

  (SEQ ID NO: 1710)

  Y L Y Y S G S T Y Y NPSLKS

  (SEQ ID NO: 1711)

  Y I Y Y S G S T Y Y NPSLKS

  (SEQ ID NO: 1712)

  Y I Y Y T G S T Y Y NPSLKS

  (SEQ ID NO: 1713)

  Y I Y Y T G S T N Y NPSLKS

  (SEQ ID NO: 1714)

  Y I Y Y S G N T N Y NPSLKS

  (SEQ ID NO: 1715)

  Y I Y Y S G S T N Y NPSLKS

  (SEQ ID NO: 1716)

  X 131 X 132 X 133 X 134 X 135 G X 136 X 137 X 138 X 139

  NPSLKS

  wherein X131 is N, F, Y, S or M; X132 is I or L;

  X133 is Y or F; X134 is Y, H or D; X135 is S or T;

  X136 is T, G, S or T; X137 is T or A; X138 is Y,

  N or H; and X139 is F or Y.

  Group 2

  (SEQ ID NO: 1717)

  L I W Y DG D N K Y Y ADSVKG

  (SEQ ID NO: 1718)

  G I S Y DG S N K N Y ADSVKG

  (SEQ ID NO: 1719)

  I I W Y DG S N K N Y ADSVKG

  (SEQ ID NO: 1720)

  L I W Y DG S N K N Y ADSVKG

  (SEQ ID NO: 1721)

  L I W Y DG S N K D Y ADSVKG

  (SEQ ID NO: 1722)

  V I W Y DG S N K D Y ADSVKG

  (SEQ ID NO: 1723)

  L I S Y DG S N K Y Y ADSVKG

  (SEQ ID NO: 1724)

  V I S Y DG S N K H Y ADSVKG

  (SEQ ID NO: 1725)

  V I S Y DG S N K Y Y ADSVKG

  (SEQ ID NO: 1726)

  V I W D DG S N K Y Y ADSVKG

  (SEQ ID NO: 1727)

  V I W D DG S N N Y Y ADSVKG

  (SEQ ID NO: 1728)

  V I W Y DG S N K Y H ADSVKG

  (SEQ ID NO: 1729)

  V I W Y DG S N K Y Y ADSVKG

  (SEQ ID NO: 1730)

  V I W N DG N N K Y Y ADSVKG

  (SEQ ID NO: 1731)

  V I W N DG S N K N Y ADSVKG

  (SEQ ID NO: 1732)

  X 140 I X 141 X 142 DG X 143 N X 144 X 145 X 146 ADSVKG

  wherein X140 is L, G, I or V; X141 is W or S;

  X142 is Y, D or N; X143 is S or D; X144 is K

  or N; X145 is Y, N, D, or H; and X146 is Y or H.

  Group 3

  (SEQ ID NO: 1733)

  W I NP P SG A T N YAQKF R G

  (SEQ ID NO: 1734)

  W I NP N SG G T N YAQKF R G

  (SEQ ID NO: 1735)

  W I NP N SG A T N YAQKF H G

  (SEQ ID NO: 1736)

  W I NP S SG D T K YAQKF Q G

  (SEQ ID NO: 1737)

  W M NP N SG A T K YAQKF Q G

  (SEQ ID NO: 1738)

  W I NP N SG A T K YAQKF Q G

  (SEQ ID NO: 1739)

  W I NP D SG G T N YAQKF Q G

  (SEQ ID NO: 1740)

  W I NP N SG G T D YAQKF Q G

  (SEQ ID NO: 1741)

  W X 147 NP X 148 SG X 149 T X 150 YAQKF X 151 G

  wherein X147 is I or M; X148 is P, N, S or D;

  X149 is A, G or D; X150 is N, K, or D; X151

  is R, H or Q.

  Group 4

  (SEQ ID NO: 1742)

  EINHS E N TNYNPSLKS

  (SEQ ID NO: 1743)

  EINHS G T TNYNPSLKS

  (SEQ ID NO: 1744)

  EINHS X 152 X 153 TNYNPSLKS

  wherein X152 is E or G; and X153 is N or T.

  Group 5

  (SEQ ID NO: 1745)

  IIYPGDS D TRYSPSFQG

  (SEQ ID NO: 1746)

  IIYPGDS E TRYSPSFQG

  (SEQ ID NO: 1747)

  IIYPGDS X 154 TRYSPSFQG

  wherein X154 is D or E.

  Group 6

  (SEQ ID NO: 1748)

  SISSSS T Y I YY A DS V KG

  (SEQ ID NO: 1749)

  SISSSS T Y I YY A DS L KG

  (SEQ ID NO: 1750)

  SISSSS S Y E YY V DS V KG

  (SEQ ID NO: 1751)

  SISSSS X 155 Y X 156 YY X 157 DS X 158 KG

  wherein X155 is T or S; X156 is I or E;

  X157 is A or V; and X158 is V or L.

  Group 7

  (SEQ ID NO: 1752)

  RI K S KTDGGTT D YAAPVKG

  (SEQ ID NO: 1753)

  RI K S KTDGGTT E YAAPVKG

  (SEQ ID NO: 1754)

  RI I G KTDGGTT D YAAPVKG

  (SEQ ID NO: 1755)

  RI X 159 X 160 KTDGGTT X 161 YAAPVKG

  wherein X159 is K or I; X160 is S or G;

  and X161 is D or E.

  Group 8

  (SEQ ID NO: 1756)

  GISGSSAGTYYADSVGK

  Group 9

  (SEQ ID NO: 1757)

  VIS D SGG S TYYADSVKG

  (SEQ ID NO: 1758)

  VIS G SGG D TYYADSVKG

  (SEQ ID NO: 1759)

  VIS X 162 SGG X 163 TYYADSVKG

  wherein X162 is D or G;

  and X163 is S or D.

  Group 10

  (SEQ ID NO: 1760)

  RTYYRSKWYNDYAVSVKS

  Group 11

  (SEQ ID NO: 1761)

  RIY I SGSTNYNPSL E N

  (SEQ ID NO: 1762)

  RIY T SGSTNYNPSL K S

  (SEQ ID NO: 1763)

  RIY X 164 SGSTNYNPSL X 165 X 166

  wherein X164 is I or T; X165 is E or K;

  and X166 is N or S.

  Group 12

  (SEQ ID NO: 1764)

  WMNPYSGSTG Y AQ N FQ G

  (SEQ ID NO: 1765)

  WMNPYSGSTG L AQ R FQ D

  (SEQ ID NO: 1766)

  WMNPYSGSTG X 167 AQ X 168 FQ X 169

  wherein X167 is Y or L; X168 is N or R;

  and X169 is G or D.

Heavy Chain CDR1

• Group 1

  (SEQ ID NO: 1767)

  SG V Y YW N

  (SEQ ID NO: 1768)

  SG V Y YW S

  (SEQ ID NO: 1769)

  SG G Y YW N

  (SEQ ID NO: 1770)

  SG G Y YW S

  (SEQ ID NO: 1771)

  SG D N TW S

  (SEQ ID NO: 1772)

  SG N Y TW S

  (SEQ ID NO: 1773)

  SG D Y TW T

  (SEQ ID NO: 1774)

  SG D Y TW S

  (SEQ ID NO: 1775)

  SG X 170 X 171 TW X 172

  wherein X170 is V, G, N or D; X171 is Y or N; and X172 is N, S or T.

  Group 2

  (SEQ ID NO: 1776)

  T YYW S

  (SEQ ID NO: 1777)

  Y YYW S

  (SEQ ID NO: 1778)

  S YYW S

  (SEQ ID NO: 1779)

  G YYW S

  (SEQ ID NO: 1780)

  G YYW T

  (SEQ ID NO: 1781)

  X 173 YYW X 174

  wherein X173 is T, S or G; and X174 is S or T.

  Group 3

  (SEQ ID NO: 1782)

  S Y GMH

  (SEQ ID NO: 1783)

  S F GMH

  (SEQ ID NO: 1784)

  T Y GMH

  (SEQ ID NO: 1785)

  F Y GMH

  (SEQ ID NO: 1786)

  X 175 X 176 GMH

  wherein X175 is S, T or F; and X176 is Y or F.

  Group 4

  (SEQ ID NO: 1787)

  SY A M S

  (SEQ ID NO: 1788)

  SY S M N

  (SEQ ID NO: 1789)

  SY S M S

  (SEQ ID NO: 1790)

  SY X 177 M X 178

  wherein X177 is A or S; and X178 is S, N or M.

  Group 5

  (SEQ ID NO: 1791)

  Y YY I H

  (SEQ ID NO: 1792)

  G YY L H

  (SEQ ID NO: 1793)

  G YY K H

  (SEQ ID NO: 1794)

  G YY T H

  (SEQ ID NO: 1795)

  G YY I H

  (SEQ ID NO: 1796)

  X 179 YY X 180 H

  wherein X179 is Y or G; and X180 is I, L, K or T.

  Group 6

  (SEQ ID NO: 1797)

  SYG I H

  (SEQ ID NO: 1798)

  SYG L H

  (SEQ ID NO: 1799)

  SYG X 181 H

  wherein X181 is L or I.

  Group 7

  (SEQ ID NO: 1800)

  NY G M H

  (SEQ ID NO: 1801)

  NY G M R

  (SEQ ID NO: 1802)

  NY N M H

  (SEQ ID NO: 1803)

  NY X 182 M X 183

  wherein X182 is G or N; and X183 is H, R or M.

  Group 8

  (SEQ ID NO: 1804)

  S YWIG

  (SEQ ID NO: 1805)

  G YWIG

  (SEQ ID NO: 1806)

  X 184 YWIG

  wherein X184 is S or G.

  Group 9

  (SEQ ID NO: 1807)

  GY Y MH

  (SEQ ID NO: 1808)

  GY F MH

  (SEQ ID NO: 1809)

  GY X 185 MH

  wherein X185 is Y or F.

  Group 10

  (SEQ ID NO: 1810)

  S Y DI N

  (SEQ ID NO: 1811)

  S H DI N

  (SEQ ID NO: 1812)

  S Y DI D

  (SEQ ID NO: 1813)

  S X 186 DI X 187

  wherein X186 is Y or H; and X187 is N or D.

  Group 11

  (SEQ ID NO: 1814)

  N YAMS

  (SEQ ID NO: 1815)

  H YAMS

  (SEQ ID NO: 1816)

  X 188 YAMS

  wherein X188 is N or H.

  Group 12

  (SEQ ID NO: 1817)

  NAWMS

  Group 13

  (SEQ ID NO: 1818)

  SSSYYWG

  Group 14

  (SEQ ID NO: 1819)

  D YYWN

  (SEQ ID NO: 1820)

  S YYWN

  (SEQ ID NO: 1821)

  X 189 YYWN

  wherein X189 is D or S.

  Group 15

  (SEQ ID NO: 1822)

  SNSA T WN

  (SEQ ID NO: 1823)

  SNSA A WN

  (SEQ ID NO: 1824)

  SNSA X 190 WN

  wherein X190 is T or A.

  Group 16

  (SEQ ID NO: 1825)

  S YDMH

  (SEQ ID NO: 1826)

  T YDMH

  (SEQ ID NO: 1827)

  X 191 YDMH

  wherein X191 is S or T.

• In some cases an antigen binding protein comprises at least one heavy chain CDR1, CDR2, or CDR3 having one of the above consensus sequences. In some cases, an antigen binding protein comprises at least one light chain CDR1, CDR2, or CDR3 having one of the above consensus sequences. In other cases, the antigen binding protein comprises at least two heavy chain CDRs according to the determined consensus sequences, and/or at least two light chain CDRs according to the determined consensus sequences. In still other cases, the antigen binding protein comprises at least three heavy chain CDRs according to the determined consensus sequences, and/or at least three light chain CDRs according to the determined consensus sequences.
Exemplary Antigen Binding Proteins
• According to one aspect, an isolated antigen binding protein comprising (a) one or more heavy chain complementary determining regions (CDRHs) comprising one or more of: (i) a CDRH1 selected from the group consisting of SEQ ID NOS 603-655; (ii) a CDRH2 selected from the group consisting of SEQ ID NOS 656-732; (iii) a CDRH3 selected from the group consisting of SEQ ID NOS 733-813; and (iv) a CDRH of (i), (ii) and (iii) that comprises ten, nine, eight, seven, six, five, four, three, two or one amino acid substitutions, deletions, insertions and combinations thereof; (b) one or more light chain complementary determining regions (CDRLs) comprising one or more of: (i) a CDRL1 selected from the group consisting of SEQ ID NOS 814-893; (ii) a CDRL2 comprising one or more of SEQ ID NOS 894-946; (iii) a CDRL3 comprising one or more of SEQ ID NOS 947-1020; and (iv) a CDRL of (i), (ii) and (iii) that comprises ten, nine, eight, seven, six, five, four, three, four, two or one amino acid substitutions, deletions or insertions and combinations thereof; or (c) one or more heavy chain CDRHs of (a) and one or more light chain CDRLs of (b).
• In another embodiment, the CDRHs have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOS 603-813, and/or the CDRLs have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOS 814-1020. In a further embodiment, the VH is selected from the group consisting of SEQ ID NOS 316-409, and/or the V_L is selected from the group consisting of SEQ ID NOS 217-315.
• According to one aspect, an isolated antigen binding protein comprising (a) one or more variable heavy chains (V_Hs) comprising one or more of: (i) SEQ ID NOS 316-409; and (ii) a V_H of (i) that comprises ten, nine, eight, seven, six, five, four, three, two or one amino acid substitutions, deletions, insertions and combinations thereof; (b) one or more variable light chains (V_Ls) selected from the group consisting of: (i) SEQ ID NOS 217-315, and (ii) a V_L of (i) that comprises ten, nine, eight, seven, six, five, four, three, two or one amino acid substitutions, deletions, insertions and combinations thereof; or (c) one or more variable heavy chains of (a) and one or more variable light chains of (b).
• In another embodiment, the variable heavy chain (V_H) has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOS 36-409, and/or the variable light chain (V_L) has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%. 98% or 99% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOS 217-315.
• In one aspect, also provided is an antigen binding protein that specifically binds to a linear or three-dimensional epitope comprising one or more amino acid residues from FGFR1c, FGRF2c and FGFR3c.
• In one aspect, also provided is an antigen binding protein that specifically binds to a linear or three-dimensional epitope comprising one or more amino acid residues from β-Klotho.
• In another aspect, also provided is an isolated antigen binding protein that specifically binds to a linear or three-dimensional epitope comprising one or more amino acid residues from both β-Klotho and one or more amino acid residues from FGFR1c, FGFR2c and FGFR3c.
• In yet another embodiment, the isolated antigen binding protein described hereinabove comprises a first amino acid sequence comprising at least one of the CDRH consensus sequences disclosed herein, and a second amino acid sequence comprising at least one of the CDRL consensus sequences disclosed herein.
• In one aspect, the first amino acid sequence comprises at least two of the CDRH consensus sequences, and/or the second amino acid sequence comprises at least two of the CDRL consensus sequences. In certain embodiments, the first and the second amino acid sequence are covalently bonded to each other.
• In a further embodiment, the first amino acid sequence of the isolated antigen binding protein comprises the CDRH3, the CDRH2 and the CDRH1 parings shown in Table 5 for each clone, and/or the second amino acid sequence of the isolated antigen binding protein comprises the CDRL3, the CDRL2 and the CDRL1 pairings shown in Table 4 or each clone.
• In a further embodiment, the antigen binding protein comprises at least two CDRH sequences of heavy chain sequences H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18, H19, H20, H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34, H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146, H46, H48, H49, H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60, H61, H62, H63, H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74, H75, H76, H77, H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88, H89, H90, H91, H92, H93 and H94, as shown in Tables 3A and 4A.
• In again a further embodiment, the antigen binding protein comprises at least two CDRL sequences of light chain sequences L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29, L30, L31, L32, L33, L34, L35, L36, L37, L38, L39, L40, L41, L42, L43, L44, L45, L46, L47, L48, L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60, L61, L62, L63, L64, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74, L75, L76, L77, L78, L79, L80, L81, L82, L83, L84, L85, L86, L87, L88, L89, L90, L91, L92, L93, L94, L95, L96, L97, L98, L99 and L100, as shown in Tables 3B and 4B.
• In still a further embodiment, the antigen binding protein comprises at least two CDRH sequences of heavy chain sequences H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18, H19, H20, H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34, H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146, H46, H48, H49, H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60, H61, H62, H63, H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74, H75, H76, H77, H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88, H89, H90, H91, H92, H93 and H94, as shown in Tables 3A and 4A, and at least two CDRLs of light chain sequences L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29, L30, L31, L32, L33, L34, L35, L36, L37, L38, L39, L40, L41, L42, L43, L44, L45, L46, L47, L48, L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60, L61, L62, L63, L64, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74, L75, L76, L77, L78, L79, L80, L81, L82, L83, L84, L85, L86, L87, L88, L89, L90, L91, L92, L93, L94, L95, L96, L97, L98, L99 and L100, as shown in Tables 3B and 4B.
• In again another embodiment, the antigen binding protein comprises the CDRH1, CDRH2, and CDRH3 sequences of heavy chain sequences H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17 or H18, H19, H20, H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34, H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H146, H46, H48, H49, H50, H51, H52, H53, H54, H55, H56, H57, H58, H59, H60, H61, H62, H63, H64, H65, H66, H67, H68, H69, H70, H71, H72, H73, H74, H75, H76, H77, H78, H79, H80, H81, H82, H83, H84, H85, H86, H87, H88, H89, H90, H91, H92, H93 and H94, as shown in Tables 3A and 4A.
• In yet another embodiment, the antigen binding protein comprises the CDRL1, CDRL2, and CDRL3 sequences of light chain sequences L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29, L30, L31, L32, L33, L34, L35, L36, L37, L38, L39, L40, L41, L42, L43, L44, L45, L46, L47, L48, L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60, L61, L62, L63, L64, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74, L75, L76, L77, L78, L79, L80, L81, L82, L83, L84, L85, L86, L87, L88, L89, L90, L91, L92, L93, L94, L95, L96, L97, L98, L99 and L100, as shown in Tables 3B and 4B.
• In yet another embodiment, the antigen binding protein comprises all six CDRs of an antigen binding protein comprising the following V_H and V_L pairs: V _L1 with V _H1; V _L2 with V _H1; V _L3 with V _H2 or V _H3; V _L4 with V _H4; V _L5 with V _H5; V _L6 with V _H6; V _L7 with V _H6; V _L8 with V _H7 or V _H8; V _L9 with V _H9; V _L10 with V _H9; V _L11 with V _H 10; V _L12 with V _H11; V _L13 with V _H12; V _L13 with V _H14; V_L14 with V _H13; V _L15 with V _H14; V_L16 with V _H15; V_L17 with V _H16; V_L18 with V _H17; V_L19 with V_H18; V_L20 with V_H19; V_L21 with V _H20; V_L22 with V_H21; V_L23 with V_H22; V_L24 with V _H23; V_L25 with V _H24; V_L26 with V _H25; V_L27 with V _H26; V_L28 with V _H27; V_L29 with V_H28; V_L30 with V_H29; V_L31 with V _H30; V_L32 with V _H31; V_L33 with V_H32; V_L34 with V_H33; V_L35 with V_H34; V_L36 with V_H35; V_L37 with V_H36; V_L38 with V_H37; V_L39 with V _H38; V_L40 with V_H39; V_L41 with V _H40; V_L42 with V_H41; V_L43 with V_H42; V_L44 with V _H43; V_L45 with V_H44; V_L46 with V_H45; V_L47 with V_H46; V_L48 with V_H47; V_L49 with V_H48; V _L50 with V_H49; V_L51 with V _H50; V_L52 with V_H51; V _L53 with V _H52; V_L54 with V _H53; V_L55 with V_H54; V _L56 with V_H54; V_L57 with V_H54; V_L58 with V_H55; V_L59 with V _H56; V_L60 with V_H57; V_L61 with V_H58; V_L62 with V_H59; V_L63 with V _H60; V_L64 with V _H1; V_L65 with V_H62; V_L66 with V_H63; V_L67 with V _H64; V_L68 with V _H65; V_L69 with V _H66; V_L70 with V_H67; V_L71 with V_H68; V_L72 with V_H69; V_L73 with V _H70; V_L74 with V _H70; V_L75 with V _H70; V_L76 with V _H71; V_L77 with V _H72; V_L78 with V _H73; V_L79 with V _H74; V_L80 with V_H75; V_L81 with V_H76; V_L82 with V_H77; V_L83 with V_H78; V_L84 with V_H79; V _L85 with V _H80; V_L86 with V _H81; V_L87 with V_H82; V_L88 with V_H86; V_L89 with V_H83; V_L90 with V_H84; V_L91 with V _H85; V_L 92 with V_H 87; V_L 93 with V_H 88; V_L 94 with V_H 88; V_L 95 with V_H 89; V_L 96 with V _H 90; V_L 97 with V_H 91; V_L 98 with V_H 92; V_L 99 with V_H 93; and V _L 100 with V_H 94; as shown in Tables 2A and 2B and Tables 4A and 4B.

• TABLE 7A
  Heavy Chain Sequences

  	Full Heavy	Full Heavy	Variable Heavy	Variable Heavy		CDRH2 SEQ ID	CDRH3 SEQ ID
  Ref	(H#)	SEQ ID NO	(VH#)	SEQ ID NO	CDRH1 SEQ ID NO	NO	NO
  63G8	H1	123	V H1	326	636	667	782
  68D3
  64A8
  67B4
  64E6	H2	136	V H2	339	637	699	783
  65E8
  65F11
  67G7
  63H11	H3	135	V H3	338	637	689	783
  63B6	H4	133	V H4	336	638	700	784
  64D4
  65C3	H5	142	V H5	345	626	701	785
  68D5
  63E6	H6	113	V H6	316	639	702	786
  66F7
  64H5	H7	126	V H7	329	614	703	787
  65G4	H8	129	V H8	332	614	703	787
  67G10v1	H9	121	V H9	324	640	704	788
  67G10v2
  66B4	H10	115	V H10	318	617	708	791
  66G2	H11	124	V H11	327	614	709	782
  68G5	H12	130	V H12	333	614	710	792
  63F5	H13	134	V H13	337	637	705	783
  66F6	H14	138	V H14	341	637	689	783
  65C1	H15	137	V H15	340	637	707	790
  64A7	H16	141	V H16	344	642	706	789
  66D4	H17	114	V H17	317	645	711	793
  65B1	H18	116	VH18	319	646	712	794
  67A4	H19	118	VH19	321	647	713	795
  65B4	H20	117	V H20	320	648	714	796
  63A10	H21	119	VH21	322	640	715	788
  65H11	H22	120	VH22	323	640	716	788
  64C8	H23	122	V H23	325	614	717	797
  65E3	H24	128	V H24	331	649	718	798
  65D4	H25	127	V H25	330	650	677	799
  65D1	H26	125	V H26	328	651	719	800
  67G8	H27	131	V H27	334	614	720	801
  65B7	H28	132	VH28	335	652	707	802
  64A6	H29	139	VH29	342	616	721	803
  65F9	H30	140	V H30	343	638	689	804
  67F5	H31	143	V H31	346	626	722	785
  64B10	H32	144	VH32	347	638	723	805
  68C8	H33	145	VH33	348	653	724	806
  67A5	H34	146	VH34	349	627	686	807
  67C10	H35	147	VH35	350	627	686	808
  64H6	H36	148	VH36	351	627	725	809
  63F9	H37	149	VH37	352	654	726	810
  67F6	H38	150	V H38	353	655	686	811
  48H11	H39	154	VH39	357	606	659	736
  52A8	H40	164	V H40	368	617	672	749
  52F8	H41	167	VH41	371	619	675	753
  49H12	H42	159	VH42	362	612	665	742
  54A1	H43	172	V H43	376	612	680	742
  55G9
  49C8	H44	156	VH44	359	609	662	739
  52H1
  60G5.2	H45	193	VH45	397	635	697	780
  49G3	H46	158	VH46	361	611	664	741
  59A10	H47	187	VH47	391	632	692	773
  49H4
  48F8	H48	153	VH48	356	605	658	735
  53B9
  56B4
  57E7
  57F11
  59C9	H49	188	VH49	392	633	693	774
  58A5
  57A4
  57F9
  51G2	H50	163	V H50	367	605	671	748
  56A7	H51	179	VH51	383	605	671	764
  56E4
  54H10	H52	173	V H52	377	623	681	759
  55D1
  48H3
  53C11
  59G10.3	H53	190	V H53	394	634	695	777
  59D10v1	H54	195	VH54	364	615	668	745
  59D10v2
  51C10.1
  60F9	H55	192	VH55	396	623	696	779
  48B4
  52D6
  61G5	H56	194	V H56	398	623	698	781
  59G10.2	H57	189	VH57	393	608	694	776
  51A8	H58	160	VH58	363	614	667	744
  53H5.2	H59	170	VH59	374	614	678	756
  53F6	H60	169	V H60	373	621	677	755
  56C11	H61	180	VH61	384	614	685	765
  49A10	H62	155	VH62	358	608	661	738
  48D4
  49G2	H63	157	VH63	360	610	663	740
  50C12
  55G11
  52C1	H64	166	V H64	370	614	674	751
  55E9	H65	176	V H65	380	625	683	762
  60D7	H66	191	V H66	395	614	677	778
  51C10.2	H67	161	VH67	365	616	669	746
  55D3	H68	174	VH68	378	624	682	760
  57B12	H69	184	VH69	388	630	689	760
  55E4	H70	175	V H70	379	604	656	752
  52C5
  60G5.1
  55E4
  49B11
  50H10
  53C1
  56G1	H71	182	V H71	386	604	656	752
  48F3	H72	152	V H72	355	604	657	734
  48C9	H73	151	V H73	354	603	656	733
  49A12
  51E2
  51E5	H74	162	V H74	366	604	670	747
  53H5.3	H75	171	VH75	375	622	679	757
  56G3.3	H76	183	VH76	387	629	688	769
  55B10
  52B8	H77	165	VH77	369	618	673	750
  55G5	H78	177	VH78	381	626	684	763
  52H2	H79	168	VH79	372	620	676	754
  56G3.2	H80	196	V H80	399	628	687	768
  56E7	H81	181	V H81	385	627	686	766
  57D9	H82	185	VH82	389	631	690	771
  48G4	H83	197	VH83	400	607	660	737
  53C3.1
  50G1	H84	178	VH84	382	613	666	743
  58C2	H85	186	V H85	390	608	691	772
  61H5	H86	198	VH86	401	629	727	769
  52B9
  50D4	H87	199	VH87	402	643	730	812
  50G5v1	H88	200	VH88	403	639	728	767
  50G5v2
  51C1	H89	201	VH89	404	604	656	752
  53C3.2	H90	202	V H90	405	641	732	775
  54H10.3	H91	203	VH91	406	645	729	813
  55A7	H92	204	VH92	407	626	673	770
  55E6	H93	205	VH93	408	605	731	761
  61E1	H94	206	VH94	409	644	690	758

• TABLE 7B
  Light Chain Sequences

  	Full Light	Full Light	Variable Light	Variable Light SEQ	CDRL1 SEQ ID	CDRL2 SEQ ID	CDRL3 SEQ ID
  Ref	(L#)	SEQ ID NO	(VH#)	ID NO	NO	NO	NO

  63G8	L1	26	V L1	229	826	922	987
  64A8
  67B4
  68D3	L2	28	V L2	231	826	922	987
  65E8	L3	37	V L3	241	859	927	988
  63H11
  64E6
  67G7
  65F11
  63B6	L4	35	V L4	239	860	928	989
  64D4
  65C3	L5	43	V L5	247	861	929	990
  68D5
  63E6	L6	14	V L6	217	862	907	991
  66F7	L7	15	V L7	218	863	907	991
  64H5	L8	30	V L8	233	864	930	992
  65G4
  67G10v1	L9	23	V L9	226	865	931	993
  67G10v2	L10	24	V L10	227	866	932	994
  66B4	L11	17	V L11	220	870	933	996
  66G2	L12	27	V L12	230	835	934	997
  68G5	L13	100	V L13	236	872	935	998
  63F5	L14	36	V L14	240	867	913	988
  66F6	L15	39	V L15	243	859	928	988
  65C1	L16	38	V L16	242	869	928	988
  64A7	L17	42	V L17	246	868	913	995
  66D4	L18	16	VL18	219	873	907	999
  65B1	L19	18	VL19	221	874	936	961
  67A4	L20	20	V L20	223	875	918	1001
  65B4	L21	19	VL21	222	876	918	1001
  63A10	L22	21	VL22	224	865	938	1002
  65H11	L23	22	V L23	225	878	931	1003
  64C8	L24	25	V L24	228	879	940	1004
  65E3	L25	32	V L25	235	864	935	1005
  65D4	L26	31	V L26	234	880	935	1006
  65D1	L27	29	V L27	232	852	925	1007
  67G8	L28	33	VL28	237	882	930	1005
  65B7	L29	34	VL29	238	883	913	1008
  64A6	L30	40	V L30	244	884	941	1009
  65F9	L31	41	V L31	245	885	908	1009
  67F5	L32	44	VL32	248	885	942	1010
  64B10	L33	45	VL33	249	886	943	963
  68C8	L34	46	VL34	250	887	909	963
  67A5	L35	47	VL35	251	888	898	1012
  67C10	L36	48	VL36	252	888	898	951
  64H6	L37	49	VL37	253	864	930	1014
  63F9	L38	50	V L38	254	889	944	1015
  67F6	L39	51	VL39	255	890	945	951
  48H11	L40	55	V L40	259	817	897	950
  52A8	L41	66	VL41	270	828	907	961
  52F8	L42	69	VL42	273	832	910	965
  49H12	L43	60	V L43	264	822	901	955
  54A1	L44	74	VL44	278	837	899	955
  55G9
  49C8	L45	57	VL45	261	819	899	952
  52H1
  60G5.2	L46	93	VL46	297	857	925	986
  49G3	L47	59	VL47	263	821	900	954
  59A10	L48	87	VL48	291	827	921	960
  49H4
  48F8	L49	54	VL49	258	816	896	949
  53B9
  56B4
  57E7
  57F11
  59C9	L50	88	V L50	292	850	922	960
  58A5
  57A4
  57F9
  51G2	L51	65	VL51	269	827	906	960
  56A7	L52	80	V L52	284	842	917	960
  56E4
  54H10.1	L53	75	V L53	279	838	913	970
  55D1
  48H3
  53C11
  59G10.3	L54	90	VL54	294	854	909	983
  51C10.1	L55	62	VL55	266	824	903	957
  59D10v1	L56	97	V L56	301	851	903	980
  59D10v2	L57	98	VL57	302	852	923	981
  60F9	L58	92	VL58	296	856	924	985
  48B4
  52D6
  61G5	L59	94	VL59	298	858	926	985
  59G10.2	L60	89	V L60	293	853	904	982
  51A8	L61	61	VL61	265	823	902	956
  53H5.2	L62	72	VL62	276	835	907	968
  53F6	L63	71	VL63	275	834	912	967
  56C11	L64	81	V L64	285	843	918	974
  49A10	L65	56	V L65	260	818	898	951
  48D4
  49G2	L66	58	V L66	262	820	898	953
  50C12
  55G11
  52C1	L67	68	VL67	272	830	909	963
  55E9	L68	78	VL68	282	840	910	972
  60D7	L69	91	VL69	295	820	898	984
  51C10.2	L70	63	V L70	267	825	904	958
  55D3	L71	76	V L71	280	839	907	971
  57B12	L72	85	V L72	289	847	907	978
  52C5	L73	95	V L73	299	831	907	964
  60G5.1	L74		V L74
  55E4	L75	77	VL75	281	831	914	964
  49B11
  50H10
  53C1
  56G1	L76	83	VL76	287	831	907	976
  48F3	L77	53	VL77	257	815	895	948
  48C9	L78	52	VL78	256	814	894	947
  49A12
  51E2
  51E5	L79	64	VL79	268	826	905	959
  53H5.3	L80	73	V L80	277	836	908	969
  56G3.3	L81	84	V L81	288	846	920	977
  55B10
  52B8	L82	67	VL82	271	829	908	962
  55G5	L83	79	VL83	283	841	916	973
  52H2	L84	70	VL84	274	833	911	966
  56G3.2	L85	99	V L85	303	845	919	962
  56E7	L86	82	VL86	286	844	900	975
  57D9	L87	86	VL87	290	848	913	976
  61H5	L88	96	VL88	300	846	913	977
  52B9
  48G4	L89	101	VL89	304	892	928	1017
  53C3.1
  50G1	L90	102	V L90	305	820	898	984
  58C2	L91	103	VL91	306	893	898	1012
  50D4	L92	104	VL92	307	839	946	1019
  50G5v1	L93	105	VL93	308	835	907	1018
  50G5v2	L94	106	VL94	309	891	915	1020
  51C1	L95	107	VL95	310	831	907	964
  53C3.2	L96	108	VL96	311	849	937	1016
  54H10.3	L97	109	VL97	312	855	939	999
  55A7	L98	110	VL98	313	871	907	1000
  55E6	L99	111	VL99	314	877	913	1011
  61E1	L100	112	V L100	315	881	907	1013

• In one aspect, the isolated antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c provided herein can be a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof.
• In another embodiment, the antibody fragment of the isolated antigen-binding proteins provided herein can be a Fab fragment, a Fab′ fragment, an F(ab)₂ fragment, an Fv fragment, a diabody, or a single chain antibody molecule.
• In a further embodiment, an isolated antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c provided herein is a human antibody and can be of the IgG1-, IgG2-IgG3- or IgG4-type.
• In another embodiment, an isolated antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises a light or a heavy chain polypeptide as set forth in Tables 1A-1B. In some embodiments, an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises a variable light or variable heavy domain such as those listed in Tables 2A-2B. In still other embodiments, an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises one, two or three CDRHs or one, two or three CDRLs as set forth in Tables 3A-3B, 4A-4B, infra. Such antigen binding proteins, and indeed any of the antigen binding proteins disclosed herein, can be PEGylated with one or more PEG molecules, for examples PEG molecules having a molecular weight selected from the group consisting of 5K, 10K, 20K, 40K, 50K, 60K, 80K, 100K or greater than 100K.
• In yet another aspect, any antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c provided herein can be coupled to a labeling group and can compete for binding to the extracellular portion of the individual protein components of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with an antigen binding protein of one of the isolated antigen binding proteins provided herein. In one embodiment, the isolated antigen binding protein provided herein can reduce blood glucose levels, decrease triglyceride and cholesterol levels or improve other glycemic parameters and cardiovascular risk factors when administered to a patient.
• As will be appreciated, for any antigen binding protein comprising more than one CDR provided in Tables 3A-3B, and 4A-4B, any combination of CDRs independently selected from the depicted sequences may be useful. Thus, antigen binding proteins with one, two, three, four, five or six of independently selected CDRs can be generated. However, as will be appreciated by those in the art, specific embodiments generally utilize combinations of CDRs that are non-repetitive, e.g., antigen binding proteins are generally not made with two CDRH2 regions, etc.
• Some of the antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are provided herein are discussed in more detail below.
Antigen Binding Proteins and Binding Epitopes and Binding Domains
• When an antigen binding protein is said to bind an epitope on a complex β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, or the extracellular domain of a protein component of such a complex, what is meant is that the antigen binding protein specifically binds to a specified portion of the complex comprising β-Klotho and an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) or to the extracellular domain of such a complex. In some embodiments, e.g., in certain cases where the antigen binding protein binds only β-Klotho, the antigen binding protein can specifically bind to a polypeptide consisting of specified residues (e.g., a specified segment of β-Klotho). In other embodiments, e.g., in certain cases where an antigen binding protein interacts with both β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, the antigen binding protein can bind residues, sequences of residues, or regions in both β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, depending on which receptor the antigen binding protein recognizes. In still other embodiments the antigen binding protein will bind residues, sequences or residues or regions of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, for example FGFR1c.
• In any of the foregoing embodiments, such an antigen binding protein does not need to contact every residue of β-Klotho or a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, or the extracellular domain of the recited proteins or complexes. Nor does every single amino acid substitution or deletion within β-Klotho or a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, or the extracellular domain of the recited proteins or complexes, necessarily significantly affect binding affinity.
• Epitope specificity and the binding domain(s) of an antigen binding protein can be determined by a variety of methods. Some methods, for example, can use truncated portions of an antigen. Other methods utilize antigen mutated at one or more specific residues, such as by employing an alanine scanning or arginine scanning-type approach or by the generation and study of chimeric proteins in which various domains, regions or amino acids are swapped between two proteins (e.g., mouse and human forms of one or more of the antigens or target proteins), or by protease protection assays.
Competing Antigen Binding Proteins
• In another aspect, antigen binding proteins are provided that compete with one of the exemplified antibodies or functional fragments for binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Such antigen binding proteins can also bind to the same epitope as one of the herein exemplified antigen binding proteins, or an overlapping epitope. Antigen binding proteins and fragments that compete with or bind to the same epitope as the exemplified antigen binding proteins are expected to show similar functional properties. The exemplified antigen binding proteins and fragments include those with the heavy and light chains H1-H94 and L1-L100, variable region domains V_L1-V _L100 and V_H1-V_H94, and CDRs provided herein, including those in Tables 1, 2, 3, and 4. Thus, as a specific example, the antigen binding proteins that are provided include those that compete with an antibody comprising:
• (a) 1, 2, 3, 4, 5 or all 6 of the CDRs listed for an antigen binding protein listed in Tables 3A and 3B, and 4A and 4B, infra;
• (b) a V_H and a V_L selected from V_L1-V _L100 and V_H1-V_H94 and listed for an antigen binding protein listed in Tables 2A and 2B; or
• (c) two light chains and two heavy chains as specified for an antigen binding protein listed in Tables 1A and 1B, infra.
• Thus, in one embodiment, the present disclosure provides antigen binding proteins, including human antibodies, that competes for binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with a reference antibody, wherein the reference antibody comprises a combination of light chain and heavy chain variable domain sequences selected from the group consisting of V_L1 with V_H1, V_L2 with V_H1, V_L3 with V_H2 or V_H3, V_L4 with V_H4, V_L5 with V_H5, V_L6 with V_H6, V_L7 with V_H6, V_L8 with V_H7 or V_H8, V_L9 with V_H9, V_L10 with V_H9, V_L11 with V_H 10, V_L12 with V_H11, V_L13 with V_H12, V_L13 with V_H14, V_L14 with V_H13, V_L15 with V_H14, V_L16 with V_H15, V_L17 with V_H16, V_L18 with V_H17, V_L19 with V_H18, V_L20 with V_H19, V_L21 with V_H20, V_L22 with V_H21, V_L23 with V_H22, V_L24 with V_H23, V_L25 with V_H24, V_L26 with V_H25, V_L27 with V_H26, V_L28 with V_H27, V_L29 with V_H28, V_L30 with V_H29, V_L31 with V_H30, V_L32 with V_H31, V_L33 with V_H32, V_L34 with V_H33, V_L35 with V_H34, V_L36 with V_H35, V_L37 with V_H36, V_L38 with V_H37, V_L39 with V_H38, V_L40 with V_H39, V_L41 with V_H40, V_L42 with V_H41, V_L43 with V_H42, V_L44 with V_H43, V_L45 with V_H44, V_L46 with V_H45, V_L47 with V_H46, V_L48 with V_H47, V_L49 with V_H48, V_L50 with V_H49, V_L51 with V_H50, 52 with V_H51, V_L53 with V_H52, V_L54 with V_H53, V_L55 with 54, and V_L56 with V_H54, V_L57 with V_H54, V_L58 with V_H55, V_L59 with V_H56, V_L60 with V_H57, V_L61 with V_H58, V_L62 with V_H59, V_L63 with V_H60, V_L64 with V_H1, V_L65 with V_H62, V_L66 with V_H63, V_L67 with V_H64, V_L68 with V_H65, V_L69 with V_H66, V_L70 with V_H67, V_L71 with V_H68, V_L72 with V_H69, V_L73 with V_H70, V_L74 with V_H70, and V_L75 with V_H70, V_L76 with V_H71, V_L77 with V_H72, V_L78 with V_H73, V_L79 with V_H74, V_L80 with V_H75, V_L81 with V_H76, V_L82 with V_H77, V_L83 with V_H78, V_L84 with V_H79, V_L85 with V_H80, V_L86 with V_H81, V_L87 with V_H82, V_L88 with V_H86, V_L89 with V_H83, V_L90 with V_H84, V_L91 with V_H85, V_L 92 with V_H 87, V_L 93 with V_H 88, V_L 94 with V_H 88, V_L 95 with V_H 89, V_L 96 with V_H 90, V_L 97 with V_H 91, V_L 98 with V_H 92, V_L 99 with V_H 93, and V_L 100 with V_H 94.
• In another embodiment, the present disclosure provides antigen binding proteins, including human antibodies, that compete for binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with a reference antibody, wherein the reference antibody is 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6, 64D4, 65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2, 68G5, 63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11, 64C8, 65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5, 67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8, 52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5, 57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3, 51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8, 53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7, 51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1, 48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2, 56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1, 53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2.
• In a further embodiment, an isolated antigen binding protein, such as a human antibody, is provided that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with substantially the same Kd as a reference antibody; initiates FGF21-like signaling in an in vitro ELK-Luciferase assay to the same degree as a reference antibody; lowers blood glucose; lowers serum lipid levels; and/or competes for binding with said reference antibody to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, wherein the reference antibody is selected from the group consisting of 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6, 64D4, 65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2, 68G5, 63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11, 64C8, 65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5, 67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8, 52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5, 57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3, 51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8, 53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7, 51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1, 48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2, 56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1, 53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2.
• The ability to compete with an antibody can be determined using any suitable assay, such as those described herein, in which antigen binding proteins 63G8, 64A8, 67B4, 68D3, 64E6, 65E8, 65F11, 67G7, 63B6, 64D4, 65C3, 68D5, 63E6, 66F7, 64H5, 65G4, 67G10v1, 67G10v2, 66B4, 66G2, 68G5, 63F5, 66F6, 65C1, 64A7, 66D4, 65B1, 67A4, 65B4, 63A10, 65H11, 64C8, 65E3, 65D4, 65D1, 67G8, 65B7, 64A6, 65F9, 67F5, 64B10, 68C8, 67A5, 67C10, 64H6, 63F9, 67F6, 48H11, 52A8, 52F8, 49H12, 54A1, 55G9, 49C8, 52H1, 60G5.2, 49G3, 59A10, 48F8, 53B9, 56B4, 57E7, 57F11, 59C9, 58A5, 57A4, 57F9, 51G2, 56A7, 56E4, 54H10, 55D1, 48H3, 53C11, 59G10.3, 51C10.1, 59D10v1, 59D10v2, 60F9, 48B4, 52D6, 61G5, 59G10.2, 51A8, 53H5.2, 53F6, 56C11, 49A10, 48D4, 49G2, 50C12, 55G11, 52C1, 55E9, 60D7, 51C10.2, 55D3, 57B12, 52C5, 60G5.1, 55E4, 49B11, 50H10, 53C1, 56G1, 48F3, 48C9, 49A12, 51E2, 51E5, 53H5.3, 56G3.3, 55B10, 52B8, 55G5, 52H2, 56G3.2, 6E7, 57D9, 61H5, 48G4, 50G1, 58C2, 50D4, 50G5v1, 50G5v2, 51C1, 53C3.2, 54H10.3, 55A7, 55E6, 61E1, 53C3.1, 49H4, and 51E2 can be used as the reference antibody.
Monoclonal Antibodies
• The antigen binding proteins that are provided include monoclonal antibodies that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and induce FGF21-like signaling to various degrees. Monoclonal antibodies can be produced using any technique known in the art, e.g., by immortalizing spleen cells harvested from the transgenic animal after completion of the immunization schedule. The spleen cells can be immortalized using any technique known in the art, e.g., by fusing them with myeloma cells to produce hybridomas. Myeloma cells for use in hybridoma-producing fusion procedures preferably are non-antibody-producing, have high fusion efficiency, and enzyme deficiencies that render them incapable of growing in certain selective media which support the growth of only the desired fused cells (hybridomas). Examples of suitable cell lines for use in mouse fusions include Sp-20, P3-X63/Ag8, P3-X63-Ag8.653, NS1/1.Ag 4 1, Sp210-Ag14, FO, NSO/U, MPC-11, MPC11-X45-GTG 1.7 and S194/5XXO Bul; examples of cell lines used in rat fusions include R210.RCY3, Y3-Ag 1.2.3, IR983F and 4B210. Other cell lines useful for cell fusions are U-266, GM1500-GRG2, LICR-LON-HMy2 and UC729-6.
• In some instances, a hybridoma cell line is produced by immunizing an animal (e.g., a transgenic animal having human immunoglobulin sequences) with an immunogen comprising (1) cell-bound receptor of CHO transfectants expressing full length human FGFR1c and β-Klotho at the cell surface, obtained by transfecting CHO cells with cDNA encoding a human full length FGFR1c polypeptide of SEQ ID NO: 4 and cDNA encoding a human β-Klotho polypeptide of SEQ ID NO: 7 with cells incubated with FGF21 prior to freezing (as shown in Example 2); or (2) cell-bound receptor of 293T transfectants expressing full length human β-Klotho and an N-terminal truncated form of human FGFR1c encompassing amino acid residue #141 to #822 polypeptide of SEQ ID NO: 4 (as shown in Example 2); harvesting spleen cells from the immunized animal; fusing the harvested spleen cells to a myeloma cell line, thereby generating hybridoma cells; establishing hybridoma cell lines from the hybridoma cells, and identifying a hybridoma cell line that produces an antibody that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and can induce FGF21-like signaling (e.g., as described in Example 4). Such hybridoma cell lines, and the monoclonal antibodies produced by them, form aspects of the present disclosure.
• Monoclonal antibodies secreted by a hybridoma cell line can be purified using any technique known in the art. Hybridomas or mAbs can be further screened to identify mAbs with particular properties, such as the ability to induce FGF21-like signaling. Examples of such screens are provided herein.
Chimeric and Humanized Antibodies
• Chimeric and humanized antibodies based upon the foregoing sequences can readily be generated. One example is a chimeric antibody, which is an antibody composed of protein segments from different antibodies that are covalently joined to produce functional immunoglobulin light or heavy chains or immunologically functional portions thereof. Generally, a portion of the heavy chain and/or light chain is identical with or homologous to a corresponding sequence in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with or homologous to a corresponding sequence in antibodies derived from another species or belonging to another antibody class or subclass. For methods relating to chimeric antibodies, see, for example, U.S. Pat. No. 4,816,567; and Morrison et al., (1985) Proc. Natl. Acad. Sci. USA 81:6851-6855, which are hereby incorporated by reference. CDR grafting is described, for example, in U.S. Pat. No. 6,180,370, U.S. Pat. No. 5,693,762, U.S. Pat. No. 5,693,761, U.S. Pat. No. 5,585,089, and U.S. Pat. No. 5,530,101.
• Generally, a goal of making a chimeric antibody is to create a chimera in which the number of amino acids from the intended patient/recipient species is maximized. One example is the “CDR-grafted” antibody, in which the antibody comprises one or more complementarity determining regions (CDRs) from a particular species or belonging to a particular antibody class or subclass, while the remainder of the antibody chain(s) is/are identical with or homologous to a corresponding sequence in antibodies derived from another species or belonging to another antibody class or subclass. For use in humans, the variable region or selected CDRs from a rodent antibody often are grafted into a human antibody, replacing the naturally-occurring variable regions or CDRs of the human antibody.
• One useful type of chimeric antibody is a “humanized” antibody. Generally, a humanized antibody is produced from a monoclonal antibody raised initially in a non-human animal. Certain amino acid residues in this monoclonal antibody, typically from non-antigen recognizing portions of the antibody, are modified to be homologous to corresponding residues in a human antibody of corresponding isotype. Humanization can be performed, for example, using various methods by substituting at least a portion of a rodent variable region for the corresponding regions of a human antibody (see, e.g., U.S. Pat. No. 5,585,089, and U.S. Pat. No. 5,693,762; Jones et al., (1986) Nature 321:522-525; Riechmann et al., (1988) Nature 332:323-27; Verhoeyen et al., (1988) Science 239:1534-1536).
• In one aspect, the CDRs of the light and heavy chain variable regions of the antibodies provided herein (e.g., in Tables 3-4 and 21-23) are grafted to framework regions (FRs) from antibodies from the same, or a different, phylogenetic species. For example, the CDRs of the heavy and light chain variable regions V_H1, V_H2, V_H3, V_H4, V_H5, V_H6, V_H7, V_H8, V_H9, V_H10, V_H11, V_H12, V_H13, V_H14, V_H15, V_H16, V_H17, V_H18, V_H19, V_H20, V_H21 V_H22, V_H23, V_H24, V_H25, V_H26, V_H27, V_H28, V_H29, V_H30, V_H31, V_H32, V_H33, V_H34, V_H35, V_H36, V_H37, V_H38, V_H39, V_H40, V_H41, V_H42, V_H43, V_H44, V_H45, V_H46, V_H47, V_H48, V_H49, V_H50, V_H51, V_H52, V_H53, V_H54, V_H55, V_H56, V_H57, V_H58, V_H59, V_H60, V_H61, V_H62, V_H63, V_H64, V_H65, V_H66, V_H67, V_H68, V_H69, V_H70, V_H71, V_H72, V_H73, V_H74, V_H75, V_H76, V_H77, V_H78, V_H79, V_H80, 81, V_H82, V_H83, V_H84, V_H85, V_H 86, V_H 87, V_H88, V_H89, V_H90, V_H91, V_H92, V_H93, and V_H94 and/or V_L1, V_L2, V_L3, V_L4, V_L5, V_L6, V_L7, V_L8, V_L9, V_L10, V_L11, V_L12, V_L13, V_L14, V_L15, V_L16, V_L17, V_L18, V_L19, V_L20, V_L21, V_L22, V_L23, V_L24, V_L25, V_L26, V_L27, V_L28, V_L29, V_L30, V_L31, V_L32, V_L33, V_L34, V_L35, V_L36, V_L37, V_L38, V_L39, V_L40, V_L41, V_L42, V_L43, V_L44, V_L45, V_L46, V_L47, V_L48, V_L49, V_L50, V_L51, V_L52, V_L53, V_L54, V_L55, V_L56, V_L57, V_L58, V_L59, V_L60, V_L61, V_L62, V_L63, V_L64, V_L65, V_L66, V_L67, V_L68, V_L69, V_L70, V_L71, V_L72, V_L73, V_L74, V_L75, V_L76, V_L77, V_L78, V_L79, V_L80, V_L81, V_L82, V_L83, V_L84, V_L85, V_L86, V_L87, V_L88, V_L89, V_L90, V_L91, V_L92, V_L93, V_L94, V_L95, V_L96, V_L97, V_L98, V_L99 and V_L100 can be grafted to consensus human FRs. To create consensus human FRs, FRs from several human heavy chain or light chain amino acid sequences can be aligned to identify a consensus amino acid sequence. In other embodiments, the FRs of a heavy chain or light chain disclosed herein are replaced with the FRs from a different heavy chain or light chain. In one aspect, rare amino acids in the FRs of the heavy and light chains of an antigen binding protein (e.g., an antibody) that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are not replaced, while the rest of the FR amino acids are replaced. A “rare amino acid” is a specific amino acid that is in a position in which this particular amino acid is not usually found in an FR. Alternatively, the grafted variable regions from the one heavy or light chain can be used with a constant region that is different from the constant region of that particular heavy or light chain as disclosed herein. In other embodiments, the grafted variable regions are part of a single chain Fv antibody.
• In certain embodiments, constant regions from species other than human can be used along with the human variable region(s) to produce hybrid antibodies.
Fully Human Antibodies
• Fully human antibodies are provided by the instant disclosure. Methods are available for making fully human antibodies specific for a given antigen without exposing human beings to the antigen (“fully human antibodies”). One specific means provided for implementing the production of fully human antibodies is the “humanization” of the mouse humoral immune system. Introduction of human immunoglobulin (Ig) loci into mice in which the endogenous Ig genes have been inactivated is one means of producing fully human monoclonal antibodies (mAbs) in mouse, an animal that can be immunized with any desirable antigen. Using fully human antibodies can minimize the immunogenic and allergic responses that can sometimes be caused by administering mouse or mouse-derived mAbs to humans as therapeutic agents.
• Fully human antibodies can be produced by immunizing transgenic animals (typically mice) that are capable of producing a repertoire of human antibodies in the absence of endogenous immunoglobulin production. Antigens for this purpose typically have six or more contiguous amino acids, and optionally are conjugated to a carrier, such as a hapten. See, e.g., Jakobovits et al., (1993) Proc. Natl. Acad. Sci. USA 90:2551-2555; Jakobovits et al., (1993) Nature 362:255-258; and Bruggermann et al., (1993) Year in Immunol. 7:33. In one example of such a method, transgenic animals are produced by incapacitating the endogenous mouse immunoglobulin loci encoding the mouse heavy and light immunoglobulin chains therein, and inserting into the mouse genome large fragments of human genome DNA containing loci that encode human heavy and light chain proteins. Partially modified animals, which have less than the full complement of human immunoglobulin loci, are then cross-bred to obtain an animal having all of the desired immune system modifications. When administered an immunogen, these transgenic animals produce antibodies that are immunospecific for the immunogen but have human rather than murine amino acid sequences, including the variable regions. For further details of such methods, see, e.g., WO96/33735 and WO94/02602. Additional methods relating to transgenic mice for making human antibodies are described in U.S. Pat. No. 5,545,807; U.S. Pat. No. 6,713,610; U.S. Pat. No. 6,673,986; U.S. Pat. No. 6,162,963; U.S. Pat. No. 5,545,807; U.S. Pat. No. 6,300,129; U.S. Pat. No. 6,255,458; U.S. Pat. No. 5,877,397; U.S. Pat. No. 5,874,299 and U.S. Pat. No. 5,545,806; in PCT publications WO91/10741, WO90/04036, and in EP 546073 and EP 546073.
• According to certain embodiments, antibodies of the invention can be prepared through the utilization of a transgenic mouse that has a substantial portion of the human antibody producing genome inserted but that is rendered deficient in the production of endogenous, murine antibodies. Such mice, then, are capable of producing human immunoglobulin molecules and antibodies and are deficient in the production of murine immunoglobulin molecules and antibodies. Technologies utilized for achieving this result are disclosed in the patents, applications and references disclosed in the specification, herein. In certain embodiments, one can employ methods such as those disclosed in PCT Published Application No. WO 98/24893 or in Mendez et al., (1997) Nature Genetics, 15:146-156, which are hereby incorporated by reference for any purpose.
• Generally, fully human monoclonal antibodies specific for a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR1c can be produced as follows. Transgenic mice containing human immunoglobulin genes are immunized with the antigen of interest, e.g. those described herein, lymphatic cells (such as B-cells) from the mice that express antibodies are obtained. Such recovered cells are fused with a myeloid-type cell line to prepare immortal hybridoma cell lines, and such hybridoma cell lines are screened and selected to identify hybridoma cell lines that produce antibodies specific to the antigen of interest. In certain embodiments, the production of a hybridoma cell line that produces antibodies specific to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR1c is provided.
• In certain embodiments, fully human antibodies can be produced by exposing human splenocytes (B or T cells) to an antigen in vitro, and then reconstituting the exposed cells in an immunocompromised mouse, e.g. SCID or nod/SCID. See, e.g., Brams et al., J. Immunol. 160: 2051-2058 (1998); Carballido et al., Nat. Med., 6: 103-106 (2000). In certain such approaches, engraftment of human fetal tissue into SCID mice (SCID-hu) results in long-term hematopoiesis and human T-cell development. See, e.g., McCune et al., Science, 241:1532-1639 (1988); Ifversen et al., Sem. Immunol., 8:243-248 (1996). In certain instances, humoral immune response in such chimeric mice is dependent on co-development of human T-cells in the animals. See, e.g., Martensson et al., Immunol., 83:1271-179 (1994). In certain approaches, human peripheral blood lymphocytes are transplanted into SCID mice. See, e.g., Mosier et al., Nature, 335:256-259 (1988). In certain such embodiments, when such transplanted cells are treated either with a priming agent, such as Staphylococcal Enterotoxin A (SEA), or with anti-human CD40 monoclonal antibodies, higher levels of B cell production is detected. See, e.g., Martensson et al., Immunol., 84: 224-230 (1995); Murphy et al., Blood, 86:1946-1953 (1995).
• Thus, in certain embodiments, fully human antibodies can be produced by the expression of recombinant DNA in host cells or by expression in hybridoma cells. In other embodiments, antibodies can be produced using the phage display techniques described herein.
• The antibodies described herein were prepared through the utilization of the XENOMOUSE® technology, as described herein. Such mice, then, are capable of producing human immunoglobulin molecules and antibodies and are deficient in the production of murine immunoglobulin molecules and antibodies. Technologies utilized for achieving the same are disclosed in the patents, applications, and references disclosed in the background section herein. In particular, however, a preferred embodiment of transgenic production of mice and antibodies therefrom is disclosed in U.S. patent application Ser. No. 08/759,620, filed Dec. 3, 1996 and International Patent Application Nos. WO 98/24893, published Jun. 11, 1998 and WO 00/76310, published Dec. 21, 2000, the disclosures of which are hereby incorporated by reference. See also Mendez et al., Nature Genetics, 15:146-156 (1997), the disclosure of which is hereby incorporated by reference.
• Through the use of such technology, fully human monoclonal antibodies to a variety of antigens have been produced. Essentially, XENOMOUSE® lines of mice are immunized with an antigen of interest (e.g. an antigen provided herein), lymphatic cells (such as B-cells) are recovered from the hyper-immunized mice, and the recovered lymphocytes are fused with a myeloid-type cell line to prepare immortal hybridoma cell lines. These hybridoma cell lines are screened and selected to identify hybridoma cell lines that produced antibodies specific to the antigen of interest. Provided herein are methods for the production of multiple hybridoma cell lines that produce antibodies specific to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR1c. Further, provided herein are characterization of the antibodies produced by such cell lines, including nucleotide and amino acid sequence analyses of the heavy and light chains of such antibodies.
• The production of the XENOMOUSE® strains of mice is further discussed and delineated in U.S. patent application Ser. No. 07/466,008, filed Jan. 12, 1990, Ser. No. 07/610,515, filed Nov. 8, 1990, Ser. No. 07/919,297, filed Jul. 24, 1992, Ser. No. 07/922,649, filed Jul. 30, 1992, Ser. No. 08/031,801, filed Mar. 15, 1993, Ser. No. 08/112,848, filed Aug. 27, 1993, Ser. No. 08/234,145, filed Apr. 28, 1994, Ser. No. 08/376,279, filed Jan. 20, 1995, 08/430,938, filed Apr. 27, 1995, Ser. No. 08/464,584, filed Jun. 5, 1995, Ser. No. 08/464,582, filed Jun. 5, 1995, Ser. No. 08/463,191, filed Jun. 5, 1995, Ser. No. 08/462,837, filed Jun. 5, 1995, Ser. No. 08/486,853, filed Jun. 5, 1995, Ser. No. 08/486,857, filed Jun. 5, 1995, Ser. No. 08/486,859, filed Jun. 5, 1995, Ser. No. 08/462,513, filed Jun. 5, 1995, Ser. No. 08/724,752, filed Oct. 2, 1996, Ser. No. 08/759,620, filed Dec. 3, 1996, U.S. Publication 2003/0093820, filed Nov. 30, 2001 and U.S. Pat. Nos. 6,162,963, 6,150,584, 6,114,598, 6,075,181, and 5,939,598 and Japanese Patent Nos. 3 068 180 B2, 3 068 506 B2, and 3 068 507 B2. See also European Patent No., EP 0 463 151 B1, grant published Jun. 12, 1996, International Patent Application No., WO 94/02602, published Feb. 3, 1994, International Patent Application No., WO 96/34096, published Oct. 31, 1996, WO 98/24893, published Jun. 11, 1998, WO 00/76310, published Dec. 21, 2000. The disclosures of each of the above-cited patents, applications, and references are hereby incorporated by reference in their entirety.
• Using hybridoma technology, antigen-specific human mAbs with the desired specificity can be produced and selected from the transgenic mice such as those described herein. Such antibodies can be cloned and expressed using a suitable vector and host cell, or the antibodies can be harvested from cultured hybridoma cells.
• Fully human antibodies can also be derived from phage-display libraries (as described in Hoogenboom et al., (1991) J. Mol. Biol. 227:381; and Marks et al., (1991) J. Mol. Biol. 222:581). Phage display techniques mimic immune selection through the display of antibody repertoires on the surface of filamentous bacteriophage, and subsequent selection of phage by their binding to an antigen of choice. One such technique is described in PCT Publication No. WO 99/10494 (hereby incorporated by reference), which describes the isolation of high affinity and functional agonistic antibodies for MPL- and msk-receptors using such an approach.
Bispecific or Bifunctional Antigen Binding Proteins
• Also provided are bispecific and bifunctional antibodies that include one or more CDRs or one or more variable regions as described above. A bispecific or bifunctional antibody in some instances can be an artificial hybrid antibody having two different heavy/light chain pairs and two different binding sites. Bispecific antibodies can be produced by a variety of methods including, but not limited to, fusion of hybridomas or linking of Fab′ fragments. See, e.g., Songsivilai & Lachmann, (1990) Clin. Exp. Immunol. 79:315-321; Kostelny et al., (1992) J. Immunol. 148:1547-1553. When an antigen binding protein of the instant disclosure binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, the binding may lead to the activation of FGF21-like activity as measured by the FGF21-like functional and signaling assays described in Examples 4-6; when such an antigen binding protein is an antibody it is referred to as an agonistic antibody.
Various Other Forms
• Some of the antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are provided in the present disclosure include variant forms of the antigen binding proteins disclosed herein (e.g., those having the sequences listed in Tables 1-4 and 6-23).
• In various embodiments, the antigen binding proteins disclosed herein can comprise one or more non-naturally occurring/encoded amino acids. For instance, some of the antigen binding proteins have one or more non-naturally occurring/encoded amino acid substitutions in one or more of the heavy or light chains, variable regions or CDRs listed in Tables 1-23. Examples of non-naturally occurring/encoded amino acids (which can be substituted for any naturally-occurring amino acid found in any sequence disclosed herein, as desired) include: 4-hydroxyproline, γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, σ-N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left-hand direction is the amino terminal direction and the right-hand direction is the carboxyl-terminal direction, in accordance with standard usage and convention. A non-limiting lists of examples of non-naturally occurring/encoded amino acids that can be inserted into an antigen binding protein sequence or substituted for a wild-type residue in an antigen binding sequence include β-amino acids, homoamino acids, cyclic amino acids and amino acids with derivatized side chains. Examples include (in the L-form or D-form; abbreviated as in parentheses): citrulline (Cit), homocitrulline (hCit), Nα-methylcitrulline (NMeCit), Nα-methylhomocitrulline (Nα-MeHoCit), ornithine (Orn), Nα-Methylornithine (Nα-MeOrn or NMeOrn), sarcosine (Sar), homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine (hQ), Nα-methylarginine (NMeR), Nα-methylleucine (Nα-MeL or NMeL), N-methylhomolysine (NMeHoK), Nα-methylglutamine (NMeQ), norleucine (Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic), Octahydroindole-2-carboxylic acid (Oic), 3-(1-naphthy)alanine (1-Nal), 3-(2-naphthyl)alanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic), 2-indanylglycine (IgI), para-iodophenylalanine (pI-Phe), para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine (Guf), glycyllysine (abbreviated “K(Nε-glycyl)” or “K(glycyl)” or “K(gly)”), nitrophenylalanine (nitrophe), aminophenylalanine (aminophe or Amino-Phe), benzylphenylalanine (benzylphe), γ-carboxyglutamic acid (γ-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine (Cpa), α-aminoadipic acid (Aad), Nα-methyl valine (NMeVal), N-α-methyl leucine (NMeLeu), Nα-methylnorleucine (NMeNle), cyclopentylglycine (Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), α, β-diaminopropionoic acid (Dpr), α, γ-diaminobutyric acid (Dab), diaminopropionic acid (Dap), cyclohexylalanine (Cha), 4-methyl-phenylalanine (MePhe), β, β-diphenyl-alanine (BiPhA), aminobutyric acid (Abu), 4-phenyl-phenylalanine (or biphenylalanine; 4Bip), α-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionic acid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid, aminopimelic acid, desmosine, diaminopimelic acid, N-ethylglycine, N-ethylaspargine, hydroxylysine, allo-hydroxylysine, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline, 4-hydroxyproline (Hyp), γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, 0-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, ω-methylarginine, 4-Amino-O-Phthalic Acid (4APA), and other similar amino acids, and derivatized forms of any of those specifically listed.
• Additionally, the antigen binding proteins can have one or more conservative amino acid substitutions in one or more of the heavy or light chains, variable regions or CDRs listed in Tables 1-4 and 6-23. Naturally-occurring amino acids can be divided into classes based on common side chain properties:
• 1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;
• 2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;
• 3) acidic: Asp, Glu;
• 4) basic: His, Lys, Arg;
• 5) residues that influence chain orientation: Gly, Pro; and
• 6) aromatic: Trp, Tyr, Phe.
• Conservative amino acid substitutions can involve exchange of a member of one of these classes with another member of the same class. Conservative amino acid substitutions can encompass non-naturally occurring/encoded amino acid residues, which are typically incorporated by chemical peptide synthesis rather than by synthesis in biological systems. See Table 8, infra. These include peptidomimetics and other reversed or inverted forms of amino acid moieties.
• Non-conservative substitutions can involve the exchange of a member of one of the above classes for a member from another class. Such substituted residues can be introduced into regions of the antibody that are homologous with human antibodies, or into the non-homologous regions of the molecule.
• In making such changes, according to certain embodiments, the hydropathic index of amino acids can be considered. The hydropathic profile of a protein is calculated by assigning each amino acid a numerical value (“hydropathy index”) and then repetitively averaging these values along the peptide chain. Each amino acid has been assigned a hydropathic index on the basis of its hydrophobicity and charge characteristics. They are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine/cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7); serine (−0.8); tryptophan (−0.9); tyrosine (−1.3); proline (−1.6); histidine (−3.2); glutamate (−3.5); glutamine (−3.5); aspartate (−3.5); asparagine (−3.5); lysine (−3.9); and arginine (−4.5).
• The importance of the hydropathic profile in conferring interactive biological function on a protein is understood in the art (see, e.g., Kyte et al., 1982, J. Mol. Biol. 157:105-131). It is known that certain amino acids can be substituted for other amino acids having a similar hydropathic index or score and still retain a similar biological activity. In making changes based upon the hydropathic index, in certain embodiments, the substitution of amino acids whose hydropathic indices are within ±2 is included. In some aspects, those which are within ±1 are included, and in other aspects, those within ±0.5 are included.
• It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity, particularly where the biologically functional protein or peptide thereby created is intended for use in immunological embodiments, as in the present case. In certain embodiments, the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with its immunogenicity and antigen-binding or immunogenicity, that is, with a biological property of the protein.
• The following hydrophilicity values have been assigned to these amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1); glutamate (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (−0.4); proline (−0.5±1); alanine (−0.5); histidine (−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5); leucine (−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5) and tryptophan (−3.4). In making changes based upon similar hydrophilicity values, in certain embodiments, the substitution of amino acids whose hydrophilicity values are within ±2 is included, in other embodiments, those which are within ±1 are included, and in still other embodiments, those within ±0.5 are included. In some instances, one can also identify epitopes from primary amino acid sequences on the basis of hydrophilicity. These regions are also referred to as “epitopic core regions.”
• Exemplary conservative amino acid substitutions are set forth in Table 8.

• TABLE 8
  Conservative Amino Acid Substitutions

  	Original Residue	Exemplary Substitutions
  	Ala	Ser
  	Arg	Lys
  	Asn	Gln, His
  	Asp	Glu
  	Cys	Ser
  	Gln	Asn
  	Glu	Asp
  	Gly	Pro
  	His	Asn, Gln
  	Ile	Leu, Val
  	Leu	Ile, Val
  	Lys	Arg, Gln, Glu
  	Met	Leu, Ile
  	Phe	Met, Leu, Tyr
  	Ser	Thr
  	Thr	Ser
  	Trp	Tyr
  	Tyr	Trp, Phe
  	Val	Ile, Leu

• A skilled artisan will be able to determine suitable variants of polypeptides as set forth herein using well-known techniques coupled with the information provided herein. One skilled in the art can identify suitable areas of the molecule that can be changed without destroying activity by targeting regions not believed to be important for activity. The skilled artisan also will be able to identify residues and portions of the molecules that are conserved among similar polypeptides. In further embodiments, even areas that can be important for biological activity or for structure can be subject to conservative amino acid substitutions without destroying the biological activity or without adversely affecting the polypeptide structure.
• Additionally, one skilled in the art can review structure-function studies identifying residues in similar polypeptides that are important for activity or structure. In view of such a comparison, one can predict the importance of amino acid residues in a protein that correspond to amino acid residues important for activity or structure in similar proteins. One skilled in the art can opt for chemically similar amino acid substitutions for such predicted important amino acid residues.
• One skilled in the art can also analyze the three-dimensional structure and amino acid sequence in relation to that structure in similar polypeptides. In view of such information, one skilled in the art can predict the alignment of amino acid residues of an antibody with respect to its three dimensional structure. One skilled in the art can choose not to make radical changes to amino acid residues predicted to be on the surface of the protein, since such residues can be involved in important interactions with other molecules. Moreover, one skilled in the art can generate test variants containing a single amino acid substitution at each desired amino acid residue. These variants can then be screened using assays for FGF21-like signaling, (including those described in the Examples provided herein) thus yielding information regarding which amino acids can be changed and which must not be changed. In other words, based on information gathered from such routine experiments, one skilled in the art can readily determine the amino acid positions where further substitutions should be avoided either alone or in combination with other mutations.
• A number of scientific publications have been devoted to the prediction of secondary structure. See, Moult, (1996) Curr. Op. in Biotech. 7:422-427; Chou et al., (1974) Biochem. 13:222-245; Chou et al., (1974) Biochemistry 113:211-222; Chou et al., (1978) Adv. Enzymol. Relat Areas Mol. Biol. 47:45-148; Chou et al., (1979) Ann. Rev. Biochem. 47:251-276; and Chou et al., (1979) Biophys. J. 26:367-384. Moreover, computer programs are currently available to assist with predicting secondary structure. One method of predicting secondary structure is based upon homology modeling. For example, two polypeptides or proteins that have a sequence identity of greater than 30%, or similarity greater than 40% can have similar structural topologies. The growth of the protein structural database (PDB) has provided enhanced predictability of secondary structure, including the potential number of folds within a polypeptide's or protein's structure. See, Holm et al., (1999) Nucl. Acid. Res. 27:244-247. It has been suggested (Brenner et al., (1997) Curr. Op. Struct. Biol. 7:369-376) that there are a limited number of folds in a given polypeptide or protein and that once a critical number of structures have been resolved, structural prediction will become dramatically more accurate.
• Additional methods of predicting secondary structure include “threading” (Jones, (1997) Curr. Opin. Struct. Biol. 7:377-387; Sippl et al., (1996) Structure 4:15-19), “profile analysis” (Bowie et al., (1991) Science 253:164-170; Gribskov et al., (1990) Meth. Enzym. 183:146-159; Gribskov et al., (1987) Proc. Nat. Acad. Sci. 84:4355-4358), and “evolutionary linkage” (See, Holm, (1999) supra; and Brenner, (1997) supra).
• In some embodiments, amino acid substitutions are made that: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity for forming protein complexes, (4) alter ligand or antigen binding affinities, and/or (4) confer or modify other physicochemical or functional properties on such polypeptides. For example, single or multiple amino acid substitutions (in some embodiments, conservative amino acid substitutions) can be made in the naturally-occurring sequence. Substitutions can be made in that portion of the antibody that lies outside the domain(s) forming intermolecular contacts. In such embodiments, conservative amino acid substitutions can be used that do not substantially change the structural characteristics of the parent sequence (e.g., one or more replacement amino acids that do not disrupt the secondary structure that characterizes the parent or native antigen binding protein). Examples of art-recognized polypeptide secondary and tertiary structures are described in Creighton, Proteins: Structures and Molecular Properties 2nd edition, 1992, W. H. Freeman & Company; Creighton, Proteins: Structures and Molecular Principles, 1984, W. H. Freeman & Company; Introduction to Protein Structure (Branden and Tooze, eds.), 2nd edition, 1999, Garland Publishing; Petsko & Ringe, Protein Structure and Function, 2004, New Science Press Ltd; and Thornton et al., (1991) Nature 354:105, which are each incorporated herein by reference.
• Additional preferred antibody variants include cysteine variants wherein one or more cysteine residues in the parent or native amino acid sequence are deleted from or substituted with another amino acid (e.g., serine). Cysteine variants are useful, inter alia when antibodies must be refolded into a biologically active conformation. Cysteine variants can have fewer cysteine residues than the native antibody, and typically have an even number to minimize interactions resulting from unpaired cysteines.
• The heavy and light chains, variable regions domains and CDRs that are disclosed can be used to prepare polypeptides that contain an antigen binding region that can specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and may induce FGF21-like signaling. For example, one or more of the CDRs listed in Tables 3-4 and 21-23 can be incorporated into a molecule (e.g., a polypeptide) covalently or noncovalently to make an immunoadhesion. An immunoadhesion can incorporate the CDR(s) as part of a larger polypeptide chain, can covalently link the CDR(s) to another polypeptide chain, or can incorporate the CDR(s) noncovalently. The CDR(s) enable the immunoadhesion to bind specifically to a particular antigen of interest (e.g., to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c or an epitope thereon).
• The heavy and light chains, variable regions domains and CDRs that are disclosed can be used to prepare polypeptides that contain an antigen binding region that can specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and may induce FGF21-like signaling. For example, one or more of the CDRs listed in Tables 3-4 and 21-23 can be incorporated into a molecule (e.g., a polypeptide) that is structurally similar to a “half” antibody comprising the heavy chain, the light chain of an antigen binding protein paired with a Fc fragment so that the antigen binding region is monovalent (like a Fab fragment) but with a dimeric Fc moiety.
• Mimetics (e.g., “peptide mimetics” or “peptidomimetics”) based upon the variable region domains and CDRs that are described herein are also provided. These analogs can be peptides, non-peptides or combinations of peptide and non-peptide regions. Fauchere, (1986) Adv. Drug Res. 15:29; Veber and Freidinger, (1985) TINS p. 392; and Evans et al., (1987) J. Med. Chem. 30:1229, which are incorporated herein by reference for any purpose. Peptide mimetics that are structurally similar to therapeutically useful peptides can be used to produce a similar therapeutic or prophylactic effect. Such compounds are often developed with the aid of computerized molecular modeling. Generally, peptidomimetics are proteins that are structurally similar to an antibody displaying a desired biological activity, such as here the ability to specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, but have one or more peptide linkages optionally replaced by a linkage selected from: —CH₂NH—, —CH₂S—, —CH₂—CH₂—, —CH—CH-(cis and trans), —COCH₂—, —CH(OH)CH₂—, and —CH₂SO—, by methods well known in the art. Systematic substitution of one or more amino acids of a consensus sequence with a D-amino acid of the same type (e.g., D-lysine in place of L-lysine) can be used in certain embodiments to generate more stable proteins. In addition, constrained peptides comprising a consensus sequence or a substantially identical consensus sequence variation can be generated by methods known in the art (Rizo and Gierasch, (1992) Ann. Rev. Biochem. 61:387), incorporated herein by reference), for example, by adding internal cysteine residues capable of forming intramolecular disulfide bridges which cyclize the peptide.
• Derivatives of the antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are described herein are also provided. The derivatized antigen binding proteins can comprise any molecule or substance that imparts a desired property to the antibody or fragment, such as increased half-life in a particular use. The derivatized antigen binding protein can comprise, for example, a detectable (or labeling) moiety (e.g., a radioactive, colorimetric, antigenic or enzymatic molecule, a detectable bead (such as a magnetic or electrodense (e.g., gold) bead), or a molecule that binds to another molecule (e.g., biotin or streptavidin), a therapeutic or diagnostic moiety (e.g., a radioactive, cytotoxic, or pharmaceutically active moiety), or a molecule that increases the suitability of the antigen binding protein for a particular use (e.g., administration to a subject, such as a human subject, or other in vivo or in vitro uses). Examples of molecules that can be used to derivatize an antigen binding protein include albumin (e.g., human serum albumin) and polyethylene glycol (PEG). Albumin-linked and PEGylated derivatives of antigen binding proteins can be prepared using techniques well known in the art. Certain antigen binding proteins include a PEGylated single chain polypeptide as described herein. In one embodiment, the antigen binding protein is conjugated or otherwise linked to transthyretin (“TTR”) or a TTR variant. The TTR or TTR variant can be chemically modified with, for example, a chemical selected from the group consisting of dextran, poly(n-vinyl pyrrolidone), polyethylene glycols, propropylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols and polyvinyl alcohols.
• Other derivatives include covalent or aggregative conjugates of the antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are disclosed herein with other proteins or polypeptides, such as by expression of recombinant fusion proteins comprising heterologous polypeptides fused to the N-terminus or C-terminus of an antigen binding protein that induces FGF21-like signaling. For example, the conjugated peptide can be a heterologous signal (or leader) polypeptide, e.g., the yeast alpha-factor leader, or a peptide such as an epitope tag. An antigen binding protein-containing fusion protein of the present disclosure can comprise peptides added to facilitate purification or identification of an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c (e.g., a poly-His tag) and that can induce FGF21-like signaling. An antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c also can be linked to the FLAG peptide as described in Hopp et al., (1988) Bio/Technology 6:1204; and U.S. Pat. No. 5,011,912. The FLAG peptide is highly antigenic and provides an epitope reversibly bound by a specific monoclonal antibody (mAb), enabling rapid assay and facile purification of expressed recombinant protein. Reagents useful for preparing fusion proteins in which the FLAG peptide is fused to a given polypeptide are commercially available (Sigma, St. Louis, Mo.).
• Multimers that comprise one or more antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c form another aspect of the present disclosure. Multimers can take the form of covalently-linked or non-covalently-linked dimers, trimers, or higher multimers. Multimers comprising two or more antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and which may induce FGF21-like signaling are contemplated for use as therapeutics, diagnostics and for other uses as well, with one example of such a multimer being a homodimer. Other exemplary multimers include heterodimers, homotrimers, heterotrimers, homotetramers, heterotetramers, etc.
• One embodiment is directed to multimers comprising multiple antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c joined via covalent or non-covalent interactions between peptide moieties fused to an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Such peptides can be peptide linkers (spacers), or peptides that have the property of promoting multimerization. Leucine zippers and certain polypeptides derived from antibodies are among the peptides that can promote multimerization of antigen binding proteins attached thereto, as described in more detail herein.
• In particular embodiments, the multimers comprise from two to four antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. The antigen binding protein moieties of the multimer can be in any of the forms described above, e.g., variants or fragments. Preferably, the multimers comprise antigen binding proteins that have the ability to specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c.
• In one embodiment, an oligomer is prepared using polypeptides derived from immunoglobulins. Preparation of fusion proteins comprising certain heterologous polypeptides fused to various portions of antibody-derived polypeptides (including the Fc domain) has been described, e.g., by Ashkenazi et al., (1991) Proc. Natl. Acad. Sci. USA 88:10535; Byrn et al., (1990) Nature 344:677; and Hollenbaugh et al., (1992) Current Protocols in Immunology, Suppl. 4, pages 10.19.1-10.19.11.
• One embodiment comprises a dimer comprising two fusion proteins created by fusing an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c to the Fc region of an antibody. The dimer can be made by, for example, inserting a gene fusion encoding the fusion protein into an appropriate expression vector, expressing the gene fusion in host cells transformed with the recombinant expression vector, and allowing the expressed fusion protein to assemble much like antibody molecules, whereupon interchain disulfide bonds form between the Fc moieties to yield the dimer.
• The term “Fc polypeptide” as used herein includes native and mutein forms of polypeptides derived from the Fc region of an antibody. Truncated forms of such polypeptides containing the hinge region that promotes dimerization also are included. Fusion proteins comprising Fc moieties (and oligomers formed therefrom) offer the advantage of facile purification by affinity chromatography over Protein A or Protein G columns.
• One suitable Fc polypeptide, described in PCT application WO 93/10151 and U.S. Pat. No. 5,426,048 and U.S. Pat. No. 5,262,522, is a single chain polypeptide extending from the N-terminal hinge region to the native C-terminus of the Fc region of a human IgG1 antibody. Another useful Fc polypeptide is the Fc mutein described in U.S. Pat. No. 5,457,035, and in Baum et al., (1994) EMBO J. 13:3992-4001. The amino acid sequence of this mutein is identical to that of the native Fc sequence presented in WO 93/10151, except that amino acid 19 has been changed from Leu to Ala, amino acid 20 has been changed from Leu to Glu, and amino acid 22 has been changed from Gly to Ala. The mutein exhibits reduced affinity for Fc receptors.
• In other embodiments, the variable portion of the heavy and/or light chains of a antigen binding protein such as disclosed herein can be substituted for the variable portion of an antibody heavy and/or light chain.
• Alternatively, the oligomer is a fusion protein comprising multiple antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with or without peptide linkers (spacer peptides). Among the suitable peptide linkers are those described in U.S. Pat. No. 4,751,180 and U.S. Pat. No. 4,935,233.
• Another method for preparing oligomeric derivatives comprising that antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c involves use of a leucine zipper. Leucine zipper domains are peptides that promote oligomerization of the proteins in which they are found. Leucine zippers were originally identified in several DNA-binding proteins (Landschultz et al., (1988) Science 240:1759-64), and have since been found in a variety of different proteins. Among the known leucine zippers are naturally occurring peptides and derivatives thereof that dimerize or trimerize. Examples of leucine zipper domains suitable for producing soluble oligomeric proteins are described in PCT application WO 94/10308, and the leucine zipper derived from lung surfactant protein D (SPD) described in Hoppe et al., (1994) FEBS Letters 344:191, hereby incorporated by reference. The use of a modified leucine zipper that allows for stable trimerization of a heterologous protein fused thereto is described in Fanslow et al., (1994) Semin. Immunol. 6:267-278. In one approach, recombinant fusion proteins comprising an antigen binding protein fragment or derivative that specifically binds to a complex comprising β-Klotho and an FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) is fused to a leucine zipper peptide are expressed in suitable host cells, and the soluble oligomeric antigen binding protein fragments or derivatives that form are recovered from the culture supernatant.
• In certain embodiments, the antigen binding protein has a K_D (equilibrium binding affinity) of less than 1 pM, 10 pM, 100 pM, 1 nM, 2 nM, 5 nM, 10 nM, 25 nM or 50 nM.
• In another aspect the instant disclosure provides an antigen binding protein having a half-life of at least one day in vitro or in vivo (e.g., when administered to a human subject). In one embodiment, the antigen binding protein has a half-life of at least three days. In another embodiment, the antibody or portion thereof has a half-life of four days or longer. In another embodiment, the antibody or portion thereof has a half-life of eight days or longer. In another embodiment, the antibody or portion thereof has a half-life of ten days or longer. In another embodiment, the antibody or portion thereof has a half-life of eleven days or longer. In another embodiment, the antibody or portion thereof has a half-life of fifteen days or longer. In another embodiment, the antibody or antigen-binding portion thereof is derivatized or modified such that it has a longer half-life as compared to the underivatized or unmodified antibody. In another embodiment, an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c contains point mutations to increase serum half life, such as described in WO 00/09560, published Feb. 24, 2000, incorporated by reference.
Glycosylation
• An antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can have a glycosylation pattern that is different or altered from that found in the native species. As is known in the art, glycosylation patterns can depend on both the sequence of the protein (e.g., the presence or absence of particular glycosylation amino acid residues, discussed below), or the host cell or organism in which the protein is produced. Particular expression systems are discussed below.
• Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tri-peptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tri-peptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose, to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine can also be used.
• Addition of glycosylation sites to the antigen binding protein is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tri-peptide sequences (for N-linked glycosylation sites). The alteration can also be made by the addition of, or substitution by, one or more serine or threonine residues to the starting sequence (for O-linked glycosylation sites). For ease, the antigen binding protein amino acid sequence can be altered through changes at the DNA level, particularly by mutating the DNA encoding the target polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
• Another means of increasing the number of carbohydrate moieties on the antigen binding protein is by chemical or enzymatic coupling of glycosides to the protein. These procedures are advantageous in that they do not require production of the protein in a host cell that has glycosylation capabilities for N- and O-linked glycosylation. Depending on the coupling mode used, the sugar(s) can be attached to (a) arginine and histidine; (b) free carboxyl groups; (c) free sulfhydryl groups such as those of cysteine; (d) free hydroxyl groups such as those of serine, threonine, or hydroxyproline; (e) aromatic residues such as those of phenylalanine, tyrosine, or tryptophan; or (0 the amide group of glutamine. These methods are described in WO 87/05330 and in Aplin & Wriston, (1981) CRC Crit. Rev. Biochem. 10:259-306.
• Removal of carbohydrate moieties present on the starting antigen binding protein can be accomplished chemically or enzymatically. Chemical deglycosylation requires exposure of the protein to the compound trifluoromethanesulfonic acid, or an equivalent compound. This treatment results in the cleavage of most or all sugars except the linking sugar (N-acetylglucosamine or N-acetylgalactosamine), while leaving the polypeptide intact. Chemical deglycosylation is described by Hakimuddin et al., (1987) Arch. Biochem. Biophys. 259:52-57 and by Edge et al., (1981) Anal. Biochem. 118:131-37. Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases as described by Thotakura et al., (1987) Meth. Enzymol. 138:350-59. Glycosylation at potential glycosylation sites can be prevented by the use of the compound tunicamycin as described by Duskin et al., (1982) J. Biol. Chem. 257:3105-09. Tunicamycin blocks the formation of protein-N-glycoside linkages.
• Hence, aspects of the present disclosure include glycosylation variants of antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c wherein the number and/or type of glycosylation site(s) has been altered compared to the amino acid sequences of the parent polypeptide. In certain embodiments, antibody protein variants comprise a greater or a lesser number of N-linked glycosylation sites than the native antibody. An N-linked glycosylation site is characterized by the sequence: Asn-X-Ser or Asn-X-Thr, wherein the amino acid residue designated as X can be any amino acid residue except proline. The substitution of amino acid residues to create this sequence provides a potential new site for the addition of an N-linked carbohydrate chain. Alternatively, substitutions that eliminate or alter this sequence will prevent addition of an N-linked carbohydrate chain present in the native polypeptide. For example, the glycosylation can be reduced by the deletion of an Asn or by substituting the Asn with a different amino acid. In other embodiments, one or more new N-linked sites are created. Antibodies typically have a N-linked glycosylation site in the Fc region.
Labels and Effector Groups
• In some embodiments, an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c comprises one or more labels. The term “labeling group” or “label” means any detectable label. Examples of suitable labeling groups include, but are not limited to, the following: radioisotopes or radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I) fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphors), enzymatic groups (e.g., horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase), chemiluminescent groups, biotinyl groups, or predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, the labeling group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labeling proteins are known in the art and can be used as is seen fit.
• The term “effector group” means any group coupled to an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c and that acts as a cytotoxic agent. Examples for suitable effector groups are radioisotopes or radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I) Other suitable groups include toxins, therapeutic groups, or chemotherapeutic groups. Examples of suitable groups include calicheamicin, auristatins, geldanamycin and cantansine. In some embodiments, the effector group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance.
• In general, labels fall into a variety of classes, depending on the assay in which they are to be detected: a) isotopic labels, which can be radioactive or heavy isotopes; b) magnetic labels (e.g., magnetic particles); c) redox active moieties; d) optical dyes; enzymatic groups (e.g. horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase); e) biotinylated groups; and f) predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags, etc.). In some embodiments, the labeling group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labeling proteins are known in the art.
• Specific labels include optical dyes, including, but not limited to, chromophores, phosphors and fluorophores, with the latter being specific in many instances. Fluorophores can be either “small molecule” fluores, or proteinaceous fluores.
• By “fluorescent label” is meant any molecule that can be detected via its inherent fluorescent properties. Suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin, methyl-coumarins, pyrene, Malacite green, stilbene, Lucifer Yellow, Cascade Blue, Texas Red, IAEDANS, EDANS, BODIPY FL, LC Red 640, Cy 5, Cy 5.5, LC Red 705, Oregon green, the Alexa-Fluor dyes (Alexa Fluor 350, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680), Cascade Blue, Cascade Yellow and R-phycoerythrin (PE) (Molecular Probes, Eugene, Oreg.), FITC, Rhodamine, and Texas Red (Pierce, Rockford, Ill.), CyS, Cy5.5, Cy7 (Amersham Life Science, Pittsburgh, Pa.). Suitable optical dyes, including fluorophores, are described in Molecular Probes Handbook by Richard P. Haugland and in subsequent editions, including Molecular Probes Handbook, A Guide to Fluorescent Probes and Labeling Technologies, 11^th edition, Johnson and Spence (eds), hereby expressly incorporated by reference.
• Suitable proteinaceous fluorescent labels also include, but are not limited to, green fluorescent protein, including a Renilla, Ptilosarcus, or Aequorea species of GFP (Chalfie et al., (1994) Science 263:802-805), eGFP (Clontech Labs., Inc., Genbank Accession Number U55762), blue fluorescent protein (BFP, Quantum Biotechnologies, Inc., Quebec, Canada; Stauber, (1998) Biotechniques 24:462-71; Heim et al., (1996) Curr. Biol. 6:178-82), enhanced yellow fluorescent protein (EYFP, Clontech Labs., Inc.), luciferase (Ichiki et al., (1993) J. Immunol. 150:5408-17), β-galactosidase (Nolan et al., (1988) Proc. Natl. Acad. Sci. U.S.A. 85:2603-07) and Renilla (WO92/15673, WO95/07463, WO98/14605, WO98/26277, WO99/49019, U.S. Pat. Nos. 5,292,658, 5,418,155, 5,683,888, 5,741,668, 5,777,079, 5,804,387, 5,874,304, 5,876,995 and 5,925,558).
Preparing of Antigen Binding Proteins
• Non-human antibodies that are provided can be, for example, derived from any antibody-producing animal, such as a mouse, rat, rabbit, goat, donkey, or non-human primate (such as a monkey, (e.g., cynomolgus or rhesus monkey) or an ape (e.g., chimpanzee)). Non-human antibodies can be used, for instance, in in vitro cell culture and cell-culture based applications, or any other application where an immune response to the antibody does not occur or is insignificant, can be prevented, is not a concern, or is desired. In certain embodiments, the antibodies can be produced by immunizing with cell bound receptor from CHO transfectants expressing full length human FGFR1c and β-Klotho at the cell surface following incubated with FGF21; or with cell bound receptor of 293T transfectants expressing full length human β-Klotho and an N-terminal truncated version of human FGFR1c encompassing amino acid residues 141 to 822 of the polypeptide of SEQ ID NO: 4; or with full-length β-Klotho, FGFR1c, FGFR2c or FGFR3c; or with the extracellular domain of β-Klotho, FGFR1c, FGFR2c or FGFR3c; or with two of β-Klotho, FGFR1c, FGFR2c, and FGFR3c; or with whole cells expressing FGFR1c, β-Klotho or both FGFR1c and β-Klotho; or with membranes prepared from cells expressing FGFR1c, β-Klotho or both FGFR1c and β-Klotho; or with fusion proteins, e.g., Fc fusions comprising FGFR1c, β-Klotho or FGFR1c and β-Klotho (or extracellular domains thereof) fused to Fc, and other methods known in the art, e.g., as described in the Examples presented herein. Alternatively, the certain non-human antibodies can be raised by immunizing with amino acids which are segments of one or more of β-Klotho, FGFR1c, FGFR2c or FGFR3c that form part of the epitope to which certain antibodies provided herein bind. The antibodies can be polyclonal, monoclonal, or can be synthesized in host cells by expressing recombinant DNA.
• Fully human antibodies can be prepared as described above by immunizing transgenic animals containing human immunoglobulin loci or by selecting a phage display library that is expressing a repertoire of human antibodies.
• The monoclonal antibodies (mAbs) can be produced by a variety of techniques, including conventional monoclonal antibody methodology, e.g., the standard somatic cell hybridization technique of Kohler & Milstein, (1975) Nature 256:495-97. Alternatively, other techniques for producing monoclonal antibodies can be employed, for example, the viral or oncogenic transformation of B-lymphocytes. One suitable animal system for preparing hybridomas is the murine system, which is a very well established procedure. Immunization protocols and techniques for isolation of immunized splenocytes for fusion are known in the art. For such procedures, B cells from immunized mice are fused with a suitable immortalized fusion partner, such as a murine myeloma cell line. If desired, rats or other mammals besides can be immunized instead of mice and B cells from such animals can be fused with the murine myeloma cell line to form hybridomas. Alternatively, a myeloma cell line from a source other than mouse can be used. Fusion procedures for making hybridomas also are well known. SLAM technology can also be employed in the production of antibodies.
• The single chain antibodies that are provided can be formed by linking heavy and light chain variable domain (Fv region) fragments via an amino acid bridge (short peptide linker), resulting in a single polypeptide chain. Such single-chain Fvs (scFvs) can be prepared by fusing DNA encoding a peptide linker between DNAs encoding the two variable domain polypeptides (V_L and V_H). The resulting polypeptides can fold back on themselves to form antigen-binding monomers, or they can form multimers (e.g., dimers, trimers, or tetramers), depending on the length of a flexible linker between the two variable domains (Kortt et al., (1997) Prot. Eng. 10:423; Kortt et al., (2001) Biomol. Eng. 18:95-108). By combining different V_L and V_H-comprising polypeptides, one can form multimeric scFvs that bind to different epitopes (Kriangkum et al., (2001) Biomol. Eng. 18:31-40). Techniques developed for the production of single chain antibodies include those described in U.S. Pat. No. 4,946,778; Bird et al., (1988) Science 242:423-26; Huston et al., (1988) Proc. Natl. Acad. Sci. U.S.A. 85:5879-83; Ward et al., (1989) Nature 334:544-46, de Graaf et al., (2002)Methods Mol Biol. 178:379-387. Single chain antibodies derived from antibodies provided herein include, but are not limited to scFvs comprising the variable domain combinations of the heavy and light chain variable regions depicted in Table 2, or combinations of light and heavy chain variable domains which include the CDRs depicted in Tables 3-4 and 6-23.
• Antibodies provided herein that are of one subclass can be changed to antibodies from a different subclass using subclass switching methods. Thus, IgG antibodies can be derived from an IgM antibody, for example, and vice versa. Such techniques allow the preparation of new antibodies that possess the antigen binding properties of a given antibody (the parent antibody), but also exhibit biological properties associated with an antibody isotype or subclass different from that of the parent antibody. Recombinant DNA techniques can be employed. Cloned DNA encoding particular antibody polypeptides can be employed in such procedures, e.g., DNA encoding the constant domain of an antibody of the desired isotype. See, e.g., Lantto et al., (2002) Methods Mol. Biol. 178:303-16.
• Accordingly, the antibodies that are provided include those comprising, for example, the variable domain combinations described, supra., having a desired isotype (for example, IgA, IgG1, IgG2, IgG3, IgG4, IgE, and IgD) as well as Fab or F(ab′)₂ fragments thereof. Moreover, if an IgG4 is desired, it can also be desired to introduce a point mutation (e.g., a mutation from CPSCP to CPPCP (SEQ ID NOs 1828 and 1829, respectively, in order of appearance) in the hinge region as described in Bloom et al., (1997) Protein Science 6:407-15, incorporated by reference herein) to alleviate a tendency to form intra-H chain disulfide bonds that can lead to heterogeneity in the IgG4 antibodies.
• Moreover, techniques for deriving antibodies having different properties (i.e., varying affinities for the antigen to which they bind) are also known. One such technique, referred to as chain shuffling, involves displaying immunoglobulin variable domain gene repertoires on the surface of filamentous bacteriophage, often referred to as phage display. Chain shuffling has been used to prepare high affinity antibodies to the hapten 2-phenyloxazol-5-one, as described by Marks et al., (1992) Nature Biotechnology 10:779-83.
• Conservative modifications can be made to the heavy and light chain variable regions described in Table 2, or the CDRs described in Tables 3A and 3B, 4A and 4B, and Tables 6-23 (and corresponding modifications to the encoding nucleic acids) to produce an antigen binding protein having functional and biochemical characteristics. Methods for achieving such modifications are described herein.
• Antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be further modified in various ways. For example, if they are to be used for therapeutic purposes, they can be conjugated with polyethylene glycol (PEGylated) to prolong the serum half-life or to enhance protein delivery. PEG can be attached directly to the antigen binding protein or it can be attached via a linker, such as a glycosidic linkage.
• Alternatively, the V region of the subject antibodies or fragments thereof can be fused with the Fc region of a different antibody molecule. The Fc region used for this purpose can be modified so that it does not bind complement, thus reducing the likelihood of inducing cell lysis in the patient when the fusion protein is used as a therapeutic agent. In addition, the subject antibodies or functional fragments thereof can be conjugated with human serum albumin to enhance the serum half-life of the antibody or fragment thereof. Another useful fusion partner for the antigen binding proteins or fragments thereof is transthyretin (TTR). TTR has the capacity to form a tetramer, thus an antibody-TTR fusion protein can form a multivalent antibody which can increase its binding avidity.
• Alternatively, substantial modifications in the functional and/or biochemical characteristics of the antigen binding proteins described herein can be achieved by creating substitutions in the amino acid sequence of the heavy and light chains that differ significantly in their effect on maintaining (a) the structure of the molecular backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulkiness of the side chain. A “conservative amino acid substitution” can involve a substitution of a native amino acid residue with a nonnative residue that has little or no effect on the polarity or charge of the amino acid residue at that position. See, Table 8, supra. Furthermore, any native residue in the polypeptide can also be substituted with alanine, as has been previously described for alanine scanning mutagenesis.
• Amino acid substitutions (whether conservative or non-conservative) of the subject antibodies can be implemented by those skilled in the art by applying routine techniques. Amino acid substitutions can be used to identify important residues of the antibodies provided herein, or to increase or decrease the affinity of these antibodies for a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c or for modifying the binding affinity of other antigen-binding proteins described herein.
Methods of Expressing Antigen Binding Proteins
• Expression systems and constructs in the form of plasmids, expression vectors, transcription or expression cassettes that comprise at least one polynucleotide as described above are also provided herein, as well host cells comprising such expression systems or constructs.
• The antigen binding proteins provided herein can be prepared by any of a number of conventional techniques. For example, antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be produced by recombinant expression systems, using any technique known in the art. See, e.g., Monoclonal Antibodies, Hybridomas: A New Dimension in Biological Analyses, (Kennet et al., eds.) Plenum Press (1980) and subsequent editions; and Harlow & Lane, (1988) supra.
• Antigen binding proteins can be expressed in hybridoma cell lines (e.g., in particular antibodies can be expressed in hybridomas) or in cell lines other than hybridomas. Expression constructs encoding the antibodies can be used to transform a mammalian, insect or microbial host cell. Transformation can be performed using any known method for introducing polynucleotides into a host cell, including, for example packaging the polynucleotide in a virus or bacteriophage and transducing a host cell with the construct by transfection procedures known in the art, as exemplified by U.S. Pat. Nos. 4,399,216; 4,912,040; 4,740,461; and 4,959,455. The optimal transformation procedure used will depend upon which type of host cell is being transformed. Methods for introduction of heterologous polynucleotides into mammalian cells are well known in the art and include, but are not limited to, dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, encapsulation of the polynucleotide(s) in liposomes, mixing nucleic acid with positively-charged lipids, and direct microinjection of the DNA into nuclei.
• Recombinant expression constructs typically comprise a nucleic acid molecule encoding a polypeptide comprising one or more of the following: one or more CDRs provided herein; a light chain constant region; a light chain variable region; a heavy chain constant region (e.g., C _H1, C _H2 and/or C_H3); and/or another scaffold portion of an antigen binding protein. These nucleic acid sequences are inserted into an appropriate expression vector using standard ligation techniques. In one embodiment, the heavy or light chain constant region is appended to the C-terminus of the anti-β-Klotho/FGFR (e.g., FGFR1c, FGFR2c or FGFR3c) complex-specific heavy or light chain variable region and is ligated into an expression vector. The vector is typically selected to be functional in the particular host cell employed (i.e., the vector is compatible with the host cell machinery, permitting amplification and/or expression of the gene can occur). In some embodiments, vectors are used that employ protein-fragment complementation assays using protein reporters, such as dihydrofolate reductase (see, for example, U.S. Pat. No. 6,270,964, which is hereby incorporated by reference). Suitable expression vectors can be purchased, for example, from Invitrogen Life Technologies or BD Biosciences. Other useful vectors for cloning and expressing the antibodies and fragments include those described in Bianchi and McGrew, (2003) Biotech. Biotechnol. Bioeng. 84:439-44, which is hereby incorporated by reference. Additional suitable expression vectors are discussed, for example, in “Gene Expression Technology,” Methods Enzymol., vol. 185, (Goeddel et al., ed.), (1990), Academic Press.
• Typically, expression vectors used in any of the host cells will contain sequences for plasmid maintenance and for cloning and expression of exogenous nucleotide sequences. Such sequences, collectively referred to as “flanking sequences” in certain embodiments will typically include one or more of the following nucleotide sequences: a promoter, one or more enhancer sequences, an origin of replication, a transcriptional termination sequence, a complete intron sequence containing a donor and acceptor splice site, a sequence encoding a leader sequence for polypeptide secretion, a ribosome binding site, a polyadenylation sequence, a polylinker region for inserting the nucleic acid encoding the polypeptide to be expressed, and a selectable marker element.
• Optionally, an expression vector can contain a “tag”-encoding sequence, i.e., an oligonucleotide molecule located at the 5′ or 3′ end of an antigen binding protein coding sequence; the oligonucleotide sequence encodes polyHis (such as hexaHis, HHHHHH (SEQ ID NO: 1830)), or another “tag” such as FLAG, HA (hemaglutinin influenza virus), or myc, for which commercially available antibodies exist. This tag is typically fused to the polypeptide upon expression of the polypeptide, and can serve as a means for affinity purification or detection of the antigen binding protein from the host cell. Affinity purification can be accomplished, for example, by column chromatography using antibodies against the tag as an affinity matrix. Optionally, the tag can subsequently be removed from the purified antigen binding protein by various means such as using certain peptidases for cleavage.
• Flanking sequences can be homologous (i.e., from the same species and/or strain as the host cell), heterologous (i.e., from a species other than the host cell species or strain), hybrid (i.e., a combination of flanking sequences from more than one source), synthetic or native. As such, the source of a flanking sequence can be any prokaryotic or eukaryotic organism, any vertebrate or invertebrate organism, or any plant, provided that the flanking sequence is functional in, and can be activated by, the host cell machinery.
• Flanking sequences useful in the vectors can be obtained by any of several methods well known in the art. Typically, flanking sequences useful herein will have been previously identified by mapping and/or by restriction endonuclease digestion and can thus be isolated from the proper tissue source using the appropriate restriction endonucleases. In some cases, the full nucleotide sequence of a flanking sequence can be known. Here, the flanking sequence can be synthesized using the methods described herein for nucleic acid synthesis or cloning.
• Whether all or only a portion of the flanking sequence is known, it can be obtained using polymerase chain reaction (PCR) and/or by screening a genomic library with a suitable probe such as an oligonucleotide and/or flanking sequence fragment from the same or another species. Where the flanking sequence is not known, a fragment of DNA containing a flanking sequence can be isolated from a larger piece of DNA that can contain, for example, a coding sequence or even another gene or genes. Isolation can be accomplished by restriction endonuclease digestion to produce the proper DNA fragment followed by isolation using agarose gel purification, column chromatography or other methods known to the skilled artisan. The selection of suitable enzymes to accomplish this purpose will be readily apparent to one of ordinary skill in the art.
• An origin of replication is typically a part of those prokaryotic expression vectors purchased commercially, and the origin aids in the amplification of the vector in a host cell. If the vector of choice does not contain an origin of replication site, one can be chemically synthesized based on a known sequence, and ligated into the vector. For example, the origin of replication from the plasmid pBR322 (GenBank Accession # J01749, New England Biolabs, Beverly, Mass.) is suitable for most gram-negative bacteria, and various viral origins (e.g., SV40, polyoma, adenovirus, vesicular stomatitus virus (VSV), or papillomaviruses such as HPV or BPV) are useful for cloning vectors in mammalian cells. Generally, the origin of replication component is not needed for mammalian expression vectors (for example, the SV40 origin is often used only because it also contains the virus early promoter).
• A transcription termination sequence is typically located 3′ to the end of a polypeptide coding region and serves to terminate transcription. Usually, a transcription termination sequence in prokaryotic cells is a G-C rich fragment followed by a poly-T sequence. While the sequence is easily cloned from a library or even purchased commercially as part of a vector, it can also be readily synthesized using methods for nucleic acid synthesis such as those described herein.
• A selectable marker gene encodes a protein necessary for the survival and growth of a host cell grown in a selective culture medium. Typical selection marker genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, tetracycline, or kanamycin for prokaryotic host cells; (b) complement auxotrophic deficiencies of the cell; or (c) supply critical nutrients not available from complex or defined media. Specific selectable markers are the kanamycin resistance gene, the ampicillin resistance gene, and the tetracycline resistance gene. Advantageously, a neomycin resistance gene can also be used for selection in both prokaryotic and eukaryotic host cells.
• Other selectable genes can be used to amplify the gene that will be expressed. Amplification is the process wherein genes that are required for production of a protein critical for growth or cell survival are reiterated in tandem within the chromosomes of successive generations of recombinant cells. Examples of suitable selectable markers for mammalian cells include dihydrofolate reductase (DHFR) and promoterless thymidine kinase genes. Mammalian cell transformants are placed under selection pressure wherein only the transformants are uniquely adapted to survive by virtue of the selectable gene present in the vector. Selection pressure is imposed by culturing the transformed cells under conditions in which the concentration of selection agent in the medium is successively increased, thereby leading to the amplification of both the selectable gene and the DNA that encodes another gene, such as an antigen binding protein that binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. As a result, increased quantities of a polypeptide such as an antigen binding protein are synthesized from the amplified DNA.
• A ribosome-binding site is usually necessary for translation initiation of mRNA and is characterized by a Shine-Dalgarno sequence (prokaryotes) or a Kozak sequence (eukaryotes). The element is typically located 3′ to the promoter and 5′ to the coding sequence of the polypeptide to be expressed.
• In some cases, such as where glycosylation is desired in a eukaryotic host cell expression system, one can manipulate the various pre- or pro-sequences to improve glycosylation or yield. For example, one can alter the peptidase cleavage site of a particular signal peptide, or add prosequences, which also can affect glycosylation. The final protein product can have, in the −1 position (relative to the first amino acid of the mature protein), one or more additional amino acids incident to expression, which may not have been totally removed. For example, the final protein product can have one or two amino acid residues found in the peptidase cleavage site, attached to the amino-terminus. Alternatively, use of some enzyme cleavage sites can result in a slightly truncated form of the desired polypeptide, if the enzyme cuts at such area within the mature polypeptide.
• Expression and cloning will typically contain a promoter that is recognized by the host organism and operably linked to the molecule encoding an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Promoters are untranscribed sequences located upstream (i.e., 5′) to the start codon of a structural gene (generally within about 100 to 1000 bp) that control transcription of the structural gene. Promoters are conventionally grouped into one of two classes: inducible promoters and constitutive promoters. Inducible promoters initiate increased levels of transcription from DNA under their control in response to some change in culture conditions, such as the presence or absence of a nutrient or a change in temperature. Constitutive promoters, on the other hand, uniformly transcribe a gene to which they are operably linked, that is, with little or no control over gene expression. A large number of promoters, recognized by a variety of potential host cells, are well known. A suitable promoter is operably linked to the DNA encoding heavy chain or light chain comprising an antigen binding protein by removing the promoter from the source DNA by restriction enzyme digestion and inserting the desired promoter sequence into the vector.
• Suitable promoters for use with yeast hosts are also well known in the art. Yeast enhancers are advantageously used with yeast promoters. Suitable promoters for use with mammalian host cells are well known and include, but are not limited to, those obtained from the genomes of viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, retroviruses, hepatitis-B virus, and Simian Virus 40 (SV40). Other suitable mammalian promoters include heterologous mammalian promoters, for example, heat-shock promoters and the actin promoter.
• Additional promoters which can be of interest include, but are not limited to: SV40 early promoter (Benoist & Chambon, (1981) Nature 290:304-310); CMV promoter (Thomsen et al., (1984) Proc. Natl. Acad. U.S.A. 81:659-663); the promoter contained in the 3′ long terminal repeat of Rous sarcoma virus (Yamamoto et al., (1980) Cell 22:787-97); herpes thymidine kinase promoter (Wagner et al., (1981) Proc. Natl. Acad. Sci. U.S.A. 78:1444-45); promoter and regulatory sequences from the metallothionine gene (Prinster et al., (1982) Nature 296:39-42); and prokaryotic promoters such as the beta-lactamase promoter (Villa-Kamaroff et al., (1978) Proc. Natl. Acad. Sci. U.S.A. 75:3727-31); or the tac promoter (DeBoer et al., (1983) Proc. Natl. Acad. Sci. U.S.A. 80:21-25). Also of interest are the following animal transcriptional control regions, which exhibit tissue specificity and have been utilized in transgenic animals: the elastase I gene control region that is active in pancreatic acinar cells (Swift et al., (1984) Cell 38:639-46; Ornitz et al., (1986) Cold Spring Harbor Symp. Quant. Biol. 50:399-409; MacDonald, (1987) Hepatology 7:425-515); the insulin gene control region that is active in pancreatic beta cells (Hanahan, (1985) Nature 315:115-22); the immunoglobulin gene control region that is active in lymphoid cells (Grosschedl et al., (1984) Cell 38:647-58; Adames et al., (1985) Nature 318:533-38; Alexander et al., (1987) Mol. Cell. Biol. 7:1436-44); the mouse mammary tumor virus control region that is active in testicular, breast, lymphoid and mast cells (Leder et al., (1986) Cell 45:485-95); the albumin gene control region that is active in liver (Pinkert et al., (1987) Genes and Devel. 1:268-76); the alpha-feto-protein gene control region that is active in liver (Krumlauf et al., (1985) Mol. Cell. Biol. 5:1639-48; Hammer et al., (1987) Science 253:53-58); the alpha 1-antitrypsin gene control region that is active in liver (Kelsey et al., (1987) Genes and Devel. 1:161-71); the beta-globin gene control region that is active in myeloid cells (Mogram et al., (1985) Nature 315:338-40; Kollias et al., (1986) Cell 46:89-94); the myelin basic protein gene control region that is active in oligodendrocyte cells in the brain (Readhead et al., (1987) Cell 48:703-12); the myosin light chain-2 gene control region that is active in skeletal muscle (Sani, (1985) Nature 314:283-86); and the gonadotropic releasing hormone gene control region that is active in the hypothalamus (Mason et al., (1986) Science 234:1372-78).
• An enhancer sequence can be inserted into the vector to increase transcription of DNA encoding light chain or heavy chain comprising an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c by higher eukaryotes, e.g., a human antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Enhancers are cis-acting elements of DNA, usually about 10-300 bp in length, that act on the promoter to increase transcription. Enhancers are relatively orientation and position independent, having been found at positions both 5′ and 3′ to the transcription unit. Several enhancer sequences available from mammalian genes are known (e.g., globin, elastase, albumin, alpha-feto-protein and insulin). Typically, however, an enhancer from a virus is used. The SV40 enhancer, the cytomegalovirus early promoter enhancer, the polyoma enhancer, and adenovirus enhancers known in the art are exemplary enhancing elements for the activation of eukaryotic promoters. While an enhancer can be positioned in the vector either 5′ or 3′ to a coding sequence, it is typically located at a site 5′ from the promoter. A sequence encoding an appropriate native or heterologous signal sequence (leader sequence or signal peptide) can be incorporated into an expression vector, to promote extracellular secretion of the antibody. The choice of signal peptide or leader depends on the type of host cells in which the antibody is to be produced, and a heterologous signal sequence can replace the native signal sequence. Examples of signal peptides that are functional in mammalian host cells include the following: the signal sequence for interleukin-7 (IL-7) described in U.S. Pat. No. 4,965,195; the signal sequence for interleukin-2 receptor described in Cosman et al., (1984) Nature 312:768-71; the interleukin-4 receptor signal peptide described in EP Patent No. 0367 566; the type I interleukin-1 receptor signal peptide described in U.S. Pat. No. 4,968,607; the type II interleukin-1 receptor signal peptide described in EP Patent No. 0 460 846.
• Expression vectors can be constructed from a starting vector such as a commercially available vector. Such vectors can but need not contain all of the desired flanking sequences. Where one or more of the flanking sequences are not already present in the vector, they can be individually obtained and ligated into the vector. Methods used for obtaining each of the flanking sequences are well known to one skilled in the art.
• After the vector has been constructed and a nucleic acid molecule encoding light chain, a heavy chain, or a light chain and a heavy chain comprising an antigen binding protein that specifically binds to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c has been inserted into the proper site of the vector, the completed vector can be inserted into a suitable host cell for amplification and/or polypeptide expression. The transformation of an expression vector for an antigen binding protein into a selected host cell can be accomplished by well known methods including transfection, infection, calcium phosphate co-precipitation, electroporation, microinjection, lipofection, DEAE-dextran mediated transfection, or other known techniques. The method selected will in part be a function of the type of host cell to be used. These methods and other suitable methods are well known to the skilled artisan, and are set forth, for example, in Sambrook et al., (2001), supra.
• A host cell, when cultured under appropriate conditions, synthesizes an antigen binding protein that can subsequently be collected from the culture medium (if the host cell secretes it into the medium) or directly from the host cell producing it (if it is not secreted). The selection of an appropriate host cell will depend upon various factors, such as desired expression levels, polypeptide modifications that are desirable or necessary for activity (such as glycosylation or phosphorylation) and ease of folding into a biologically active molecule.
• Mammalian cell lines available as hosts for expression are well known in the art and include, but are not limited to, immortalized cell lines available from the American Type Culture Collection (ATCC), including but not limited to HeLa cells, Human Embryonic Kidney 293 cells (HEK293 cells), Chinese hamster ovary (CHO) cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), and a number of other cell lines. In certain embodiments, cell lines can be selected through determining which cell lines have high expression levels and constitutively produce antigen binding proteins with desirable binding properties (e.g., the ability to bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c). In another embodiment, a cell line from the B cell lineage that does not make its own antibody but has a capacity to make and secrete a heterologous antibody can be selected. The ability to induce FGF21-like signaling can also form a selection criterion.
Uses of Antigen Binding Proteins for Diagnostic and Therapeutic Purposes
• The antigen binding proteins disclosed herein are useful for detecting to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in biological samples and identification of cells or tissues that produce one or more of β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. For instance, the antigen binding proteins disclosed herein can be used in diagnostic assays, e.g., binding assays to detect and/or quantify a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c expressed in a tissue or cell.
• Antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can also be used in treatment of diseases related to FGF21-like signaling in a patient in need thereof, such as type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, and metabolic syndrome. By forming a signaling complex comprising an antigen binding protein and a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, the natural in vivo activity of FGF21, which associates with a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in vivo to initiate signaling, can be mimicked and/or enhanced, leading to therapeutic effects.
Indications
• A disease or condition associated with human FGF21 includes any disease or condition whose onset in a patient is influenced by, at least in part, the lack of or therapeutically insufficient induction of FGF21-like signaling, which is initiated in vivo by the formation of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. The severity of the disease or condition can also be decreased by the induction of FGF21-like signaling. Examples of diseases and conditions that can be treated with the antigen binding proteins provided herein include type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, and metabolic syndrome.
• The antigen binding proteins described herein can be used to treat type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease, and metabolic syndrome, or can be employed as a prophylactic treatment administered, e.g., daily, weekly, biweekly, monthly, bimonthly, biannually, etc to prevent or reduce the frequency and/or severity of symptoms, e.g., elevated plasma glucose levels, elevated triglycerides and/or cholesterol levels, thereby providing an improved glycemic and cardiovascular risk factor profile.
Diagnostic Methods
• The antigen binding proteins described herein can be used for diagnostic purposes to detect, diagnose, or monitor diseases and/or conditions associated with FGFR1c, FGFR2c, FGFR3c, β-Klotho, FGF21 and/or complexes comprising combinations thereof. Also provided are methods for the detection of the presence of to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in a sample using classical immunohistological methods known to those of skill in the art (e.g., Tijssen, (1985) “Practice and Theory of Enzyme Immunoassays” in Laboratory Techniques in Biochemistry and Molecular Biology, 15 (Burdon & van Knippenberg, eds.), Elsevier Biomedical); Zola, (1987) Monoclonal Antibodies: A Manual of Techniques, pp. 147-58 (CRC Press, Inc.); Jalkanen et al., (1985) J. Cell. Biol. 101:976-85; Jalkanen et al., (1987) J. Cell Biol. 105:3087-96). The detection of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be performed in vivo or in vitro.
• Diagnostic applications provided herein include use of the antigen binding proteins to detect expression/formation of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c, and/or binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Examples of methods useful in the detection of the presence of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA).
• For diagnostic applications, the antigen binding protein typically will be labeled with a detectable labeling group. Suitable labeling groups include, but are not limited to, the following: radioisotopes or radionuclides (e.g., ³H, ¹⁴C, ¹⁵N, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I), fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphors), enzymatic groups (e.g., horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase), chemiluminescent groups, biotinyl groups, or predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, the labeling group is coupled to the antigen binding protein via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labeling proteins are known in the art and can be used.
• In another aspect, an antigen binding protein can be used to identify a cell or cells that express a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In a specific embodiment, the antigen binding protein is labeled with a labeling group and the binding of the labeled antigen binding protein to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c is detected. In a further specific embodiment, the binding of the antigen binding protein to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c detected in vivo. In a further specific embodiment, the antigen binding protein is isolated and measured using techniques known in the art. See, for example, Harlow & Lane, (1988) supra; Current Protocols In Immunology (John E. Coligan, ed), John Wiley & Sons (1993 ed., and supplements and/or updates). Another aspect provides for detecting the presence of a test molecule that competes for binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with the antigen binding proteins provided, as disclosed herein. An example of one such assay could involve detecting the amount of free antigen binding protein in a solution containing an amount of a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in the presence or absence of the test molecule. An increase in the amount of free antigen binding protein (i.e., the antigen binding protein not bound to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c) would indicate that the test molecule is capable of competing for binding to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c with the antigen binding protein. In one embodiment, the antigen binding protein is labeled with a labeling group. Alternatively, the test molecule is labeled and the amount of free test molecule is monitored in the presence and absence of an antigen binding protein.
Methods of Treatment: Pharmaceutical Formulations and Routes of Administration
• Methods of using the disclosed antigen binding proteins are also provided. In some methods, an antigen binding protein is provided to a patient, which induces FGF21-like signaling.
• Pharmaceutical compositions that comprise a therapeutically effective amount of one or a plurality of the antigen binding proteins and a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative, and/or adjuvant are also provided. In addition, methods of treating a patient by administering such pharmaceutical composition are included. The term “patient” includes human patients.
• Acceptable formulation materials are nontoxic to recipients at the dosages and concentrations employed. In specific embodiments, pharmaceutical compositions comprising a therapeutically effective amount of human antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are provided.
• In certain embodiments, acceptable formulation materials preferably are nontoxic to recipients at the dosages and concentrations employed. In certain embodiments, the pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as Pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol sorbitol); delivery vehicles; diluents; excipients and/or pharmaceutical adjuvants. See, e.g., Remington's Pharmaceutical Sciences, 18th Edition, (A. R. Gennaro, ed.), 1990, Mack Publishing Company, and subsequent editions.
• In certain embodiments, the optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format and desired dosage. See, for example, Remington's Pharmaceutical Sciences, supra. In certain embodiments, such compositions can influence the physical state, stability, rate of in vivo release and rate of in vivo clearance of the antigen binding proteins disclosed. In certain embodiments, the primary vehicle or carrier in a pharmaceutical composition can be either aqueous or non-aqueous in nature. For example, a suitable vehicle or carrier can be water for injection, physiological saline solution or artificial cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. In specific embodiments, pharmaceutical compositions comprise Tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, and can further include sorbitol or a suitable substitute. In certain embodiments, compositions comprising antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents (see, Remington's Pharmaceutical Sciences, supra for examples of suitable formulation agents) in the form of a lyophilized cake or an aqueous solution. Further, in certain embodiments, antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be formulated as a lyophilizate using appropriate excipients such as sucrose. The pharmaceutical compositions can be selected for parenteral delivery.
• Alternatively, the compositions can be selected for inhalation or for delivery through the digestive tract, such as orally. Preparation of such pharmaceutically acceptable compositions is within the skill of the art.
• The formulation components are present preferably in concentrations that are acceptable to the site of administration. In certain embodiments, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8.
• When parenteral administration is contemplated, the therapeutic compositions can be provided in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising the desired antigen binding protein in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is sterile distilled water in which the antigen binding protein is formulated as a sterile, isotonic solution, properly preserved. In certain embodiments, the preparation can involve the formulation of the desired molecule with an agent, such as injectable microspheres, bio-erodible particles, polymeric compounds (such as polylactic acid or polyglycolic acid), beads or liposomes, that can provide controlled or sustained release of the product which can be delivered via depot injection. In certain embodiments, hyaluronic acid can also be used, which can have the effect of promoting sustained duration in the circulation. In certain embodiments, implantable drug delivery devices can be used to introduce the desired antigen binding protein.
• Certain pharmaceutical compositions are formulated for inhalation. In some embodiments, antigen binding proteins that bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c are formulated as a dry, inhalable powder. In specific embodiments, antigen binding protein inhalation solutions can also be formulated with a propellant for aerosol delivery. In certain embodiments, solutions can be nebulized. Pulmonary administration and formulation methods therefore are further described in International Patent Application No. PCT/US94/001875, which is incorporated by reference and describes pulmonary delivery of chemically modified proteins. Some formulations can be administered orally. Antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c that are administered in this fashion can be formulated with or without carriers customarily used in the compounding of solid dosage forms such as tablets and capsules. In certain embodiments, a capsule can be designed to release the active portion of the formulation at the point in the gastrointestinal tract when bioavailability is maximized and pre-systemic degradation is minimized. Additional agents can be included to facilitate absorption of an antigen binding protein. Diluents, flavorings, low melting point waxes, vegetable oils, lubricants, suspending agents, tablet disintegrating agents, and binders can also be employed.
• Some pharmaceutical compositions comprise an effective quantity of one or a plurality of human antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in a mixture with non-toxic excipients that are suitable for the manufacture of tablets. By dissolving the tablets in sterile water, or another appropriate vehicle, solutions can be prepared in unit-dose form. Suitable excipients include, but are not limited to, inert diluents, such as calcium carbonate, sodium carbonate or bicarbonate, lactose, or calcium phosphate; or binding agents, such as starch, gelatin, or acacia; or lubricating agents such as magnesium stearate, stearic acid, or talc.
• Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations involving antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c in sustained- or controlled-delivery formulations. Techniques for formulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. See, for example, International Patent Application No. PCT/US93/00829, which is incorporated by reference and describes controlled release of porous polymeric microparticles for delivery of pharmaceutical compositions. Sustained-release preparations can include semipermeable polymer matrices in the form of shaped articles, e.g., films, or microcapsules. Sustained release matrices can include polyesters, hydrogels, polylactides (as disclosed in U.S. Pat. No. 3,773,919 and European Patent Application Publication No. EP 058481, each of which is incorporated by reference), copolymers of L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al., (1983) Biopolymers 2:547-556), poly (2-hydroxyethyl-inethacrylate) (Langer et al., (1981) J. Biomed. Mater. Res. 15:167-277 and Langer, (1982) Chem. Tech. 12:98-105), ethylene vinyl acetate (Langer et al., (1981) supra) or poly-D(−)-3-hydroxybutyric acid (European Patent Application Publication No. EP 133988). Sustained release compositions can also include liposomes that can be prepared by any of several methods known in the art. See, e.g., Eppstein et al., (1985) Proc. Natl. Acad. Sci. U.S.A. 82:3688-3692; European Patent Application Publication Nos. EP 036676; EP 088046 and EP 143949, incorporated by reference.
• Pharmaceutical compositions used for in vivo administration are typically provided as sterile preparations. Sterilization can be accomplished by filtration through sterile filtration membranes. When the composition is lyophilized, sterilization using this method can be conducted either prior to or following lyophilization and reconstitution. Compositions for parenteral administration can be stored in lyophilized form or in a solution. Parenteral compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.
• In certain embodiments, cells expressing a recombinant antigen binding protein as disclosed herein are encapsulated for delivery (see, Tao et al., Invest. Ophthalmol Vis Sci (2002) 43:3292-3298 and Sieving et al., Proc. Natl. Acad. Sciences USA (2006) 103:3896-3901).
• In certain formulations, an antigen binding protein has a concentration of between 10 mg/ml and 150 mg/ml. Some formulations contain a buffer, sucrose and polysorbate. An example of a formulation is one containing 50-100 mg/ml of antigen binding protein, 5-20 mM sodium acetate, 5-10% w/v sucrose, and 0.002-0.008% w/v polysorbate. Certain, formulations, for instance, contain 1-100 mg/ml of an antigen binding protein in 9-11 mM sodium acetate buffer, 8-10% w/v sucrose, and 0.005-0.006% w/v polysorbate. The pH of certain such formulations is in the range of 4.5-6. Other formulations can have a pH of 5.0-5.5.
• Once the pharmaceutical composition has been formulated, it can be stored in sterile vials as a solution, suspension, gel, emulsion, solid, crystal, or as a dehydrated or lyophilized powder. Such formulations can be stored either in a ready-to-use form or in a form (e.g., lyophilized) that is reconstituted prior to administration. Kits for producing a single-dose administration unit are also provided. Certain kits contain a first container having a dried protein and a second container having an aqueous formulation. In certain embodiments, kits containing single and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes) are provided. The therapeutically effective amount of an antigen binding protein-containing pharmaceutical composition to be employed will depend, for example, upon the therapeutic context and objectives. One skilled in the art will appreciate that the appropriate dosage levels for treatment will vary depending, in part, upon the molecule delivered, the indication for which the antigen binding protein is being used, the route of administration, and the size (body weight, body surface or organ size) and/or condition (the age and general health) of the patient. In certain embodiments, the clinician can titer the dosage and modify the route of administration to obtain the optimal therapeutic effect.
• A typical dosage can range from about 1 μg/kg to up to about 30 mg/kg or more, depending on the factors mentioned above. In specific embodiments, the dosage can range from 10 μg/kg up to about 35 mg/kg, optionally from 0.1 mg/kg up to about 35 mg/kg, alternatively from 0.3 mg/kg up to about 20 mg/kg. In some applications, the dosage is from 0.5 mg/kg to 20 mg/kg and in other applications the dosage is from 21-100 mg/kg. In some instances, an antigen binding protein is dosed at 0.3-20 mg/kg. The dosage schedule in some treatment regimes is at a dose of 0.3 mg/kg qW-20 mg/kg qW.
• Dosing frequency will depend upon the pharmacokinetic parameters of the particular antigen binding protein in the formulation used. Typically, a clinician administers the composition until a dosage is reached that achieves the desired effect. The composition can therefore be administered as a single dose, or as two or more doses (which can but need not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter. Appropriate dosages can be ascertained through use of appropriate dose-response data. In certain embodiments, the antigen binding proteins can be administered to patients throughout an extended time period. Chronic administration of an antigen binding protein minimizes the adverse immune or allergic response commonly associated with antigen binding proteins that are not fully human, for example an antibody raised against a human antigen in a non-human animal, for example, a non-fully human antibody or non-human antibody produced in a non-human species.
• The route of administration of the pharmaceutical composition is in accord with known methods, e.g., orally, through injection by intravenous, intraperitoneal, intracerebral (intra-parenchymal), intracerebroventricular, intramuscular, intra-ocular, intraarterial, intraportal, or intralesional routes; by sustained release systems or by implantation devices. In certain embodiments, the compositions can be administered by bolus injection or continuously by infusion, or by implantation device.
• The composition also can be administered locally via implantation of a membrane, sponge or another appropriate material onto which the desired molecule has been absorbed or encapsulated. In certain embodiments, where an implantation device is used, the device can be implanted into any suitable tissue or organ, and delivery of the desired molecule can be via diffusion, timed-release bolus, or continuous administration.
• It also can be desirable to use antigen binding protein pharmaceutical compositions ex vivo. In such instances, cells, tissues or organs that have been removed from the patient are exposed to antigen binding protein pharmaceutical compositions after which the cells, tissues and/or organs are subsequently implanted back into the patient.
• In particular, antigen binding proteins that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c can be delivered by implanting certain cells that have been genetically engineered, using methods such as those described herein and known in the art, to express and secrete the polypeptide. In certain embodiments, such cells can be animal or human cells, and can be autologous, heterologous, or xenogeneic. In certain embodiments, the cells can be immortalized. In other embodiments, in order to decrease the chance of an immunological response, the cells can be encapsulated to avoid infiltration of surrounding tissues. In further embodiments, the encapsulation materials are typically biocompatible, semi-permeable polymeric enclosures or membranes that allow the release of the protein product(s) but prevent the destruction of the cells by the patient's immune system or by other detrimental factors from the surrounding tissues.
Combination Therapies
• In another aspect, the present disclosure provides a method of treating a subject for diabetes with a therapeutic antigen binding protein of the present disclosure, such as the fully human therapeutic antibodies described herein, together with one or more other treatments. In one embodiment, such a combination therapy achieves an additive or synergistic effect. The antigen binding proteins can be administered in combination with one or more of the type 2 diabetes or obesity treatments currently available. These treatments for diabetes include biguanide (metaformin), and sulfonylureas (such as glyburide, glipizide). Additional treatments directed at maintaining glucose homeostasis include PPAR gamma agonists (pioglitazone, rosiglitazone); glinides (meglitinide, repaglinide, and nateglinide); DPP-4 inhibitors (Januvia® and Onglyza®) and alpha glucosidase inhibitors (acarbose, voglibose).
• Additional combination treatments for diabetes include injectable treatments such as insulin and incretin mimetics (Byetta®, Exenatide®), other GLP-1 (glucagon-like peptide) analogs such as Victoza® (liraglutide), other GLP-1R agonists and Symlin® (pramlintide).
• Additional combination treatments directed at weight loss include Meridia® and Xenical®.
EXAMPLES
• The following examples, including the experiments conducted and the results achieved, are provided for illustrative purposes only and are not to be construed as limiting.
Example 1 Preparation of FGFR1c and β-Klotho Over Expressing Cells for Use as an Antigen
• Nucleic acid sequences encoding the full length human FGFR1c polypepetide (SEQ ID NO: 4; FIGS. 1A-1B) and a separate sequence encoding the full length human β-Klotho polypeptide (SEQ ID NO: 7; FIGS. 2A-2C) were subcloned into suitable mammalian cell expression vectors (e.g., pcDNA3.1 Zeo, pcDNA3.1 Hyg (Invitrogen, Carlsbad, Calif.) or pDSRa24. The pDSRa24 vector contains SV40 early promoter/enhancer for expressing the gene of interest and a mouse DHFR expression cassette for selection in CHO DHFR (−) host cells such as AM1/D CHO (a derivative of DG44, CHO DHFR (−)).
• AM-1/D CHO cells were transfected with linearized DNAs of huFGFR1c and hufβ-Klotho in standard mammalian cell expression vectors e.g. pcDNA3.1 puro and pcDNA3.1 Hyg with Lipofectamine 2000 (Invitrogen, Carlsbad Calif.). The transfected cells were trypsinized 2 days after transfection and seeded into media containing the corresponding selection drugs i.e. puromycin and hygromycin. After 2 weeks, the resulting transfected colonies were trypsinized and pooled. Single cell clones from the pools were isolated and screened with antibodies to huFGFR1c and huβKlotho in FACS and Clone 16 was selected due to the high level and balanced expression of the two receptor components.
• 2×10e9 fresh cells from Clone 16 were harvested from roller bottles into a smaller volume in PBS and incubated with 10 μg/ml recombinant FGF21 (Amgen, Thousand Oaks Calif.) at 4 C for 1 hours to form complex with the cell surface receptors. The cells were washed twice with cold PBS, pelleted by centrifugation and frozen in individual vials at 2×10e8 cells for immunization.
• HEK 293T cells were transfected with DNA expressing a truncated version of huFGFR1c (a signal peptide V_H21 was joined to the remaining FGFR1c from amino acid residue #141 to #822 (in SEQ ID NO: 4) with a deletion that removed both the D1 domain and the acidic box (AB) and DNA expressing the full length huβ-Klotho in pcDNA3.1 series or pTT5 (an expression vector developed by Durocher, NRCC, with CMV promoter and EBV ori) based vector for transient expression. The removal of the D1-AB on FGFR1c was designed to expose epitopes on FGFR1c (e.g., in the D2 and D3 domains) that may be masked by this auto-inhibitory domain (see Mohammadi et al., (2005) Cytokine Growth Factor Reviews, 16, 107-137; Gupte et al., (2011) J. Mol. Biol. 408:491-502).
• The expression of β-Klotho and truncated FGFR1c in the transfected 293T cells was verified by the respective specific antibodies in FACS and cells were harvested on day 3 post-transfection and frozen as cell pellet into aliquots for immunization.
• Stable CHO or transiently transfected HEK 293T cells expressing FGFR1c and β-Klotho individually or together were also generated and used for titering mouse sera by FACS after immunization and for binding screens of the hybridoma supernatants by FMAT (see Example 3).
Example 2 Preparation of Monoclonal Antibodies
• Immunizations were conducted using one or more suitable forms of FGF21 receptor antigen, including: (1) cell-bound receptor of CHO transfectants expressing full length human FGFR1c and β-Klotho at the cell surface, obtained by transfecting CHO cells with cDNA encoding a human full length FGFR1c polypeptide of SEQ ID NO: 4 (see also FIGS. 1a-b ) and cDNA encoding a human β-Klotho polypeptide of SEQ ID NO: 7 (see also FIGS. 2a-c ) in a balanced ratio with cells and incubated with FGF21 prior to freezing; (2) cell-bound receptor of 293T transfectants expressing full length human β-Klotho and an N-terminal truncated form of human FGFR1c encompassing amino acid residues 141-822 polypeptide of SEQ ID NO: 4 (D1 domain of FGFR1c deleted).
• A suitable amount of immunogen (i.e., 3-4×10⁶ cells/mouse of stably transfected CHO cells or transiently transfected 293T cells mentioned above was used for initial immunization in XENOMOUSE® according to the methods disclosed in U.S. patent application Ser. No. 08/759,620, filed Dec. 3, 1996 and International Patent Application Nos. WO 98/24893, and WO 00/76310, the disclosures of which are incorporated by reference. Following the initial immunization, subsequent boost immunizations of immunogen (1.7×10⁶ FGF21R transfected cells/mouse) were administered on a schedule and for the duration necessary to induce a suitable anti-FGF21R titer in the mice. Titers were determined by a suitable method, for example, by enzyme immunoassay, fluorescence activated cell sorting (FACS), or by other methods (including combinations of enzyme immunoassays and FACS).
• Animals exhibiting suitable titers were identified, and lymphocytes were obtained from draining lymph nodes and, if necessary, pooled for each cohort. Lymphocytes were dissociated from lymphoid tissue by grinding in a suitable medium (for example, Dulbecco's Modified Eagle Medium; DMEM; obtainable from Invitrogen, Carlsbad, Calif.) to release the cells from the tissues, and suspended in DMEM. B cells were selected and/or expanded using standard methods, and fused with suitable fusion partner, for example, nonsecretory myeloma P3X63Ag8.653 cells (American Type Culture Collection CRL 1580; Kearney et al, (1979) J. Immunol. 123:1548-1550), using techniques that were known in the art.
• In one suitable fusion method, lymphocytes were mixed with fusion partner cells at a ratio of 1:4. The cell mixture was gently pelleted by centrifugation at 400×g for 4 minutes, the supernatant decanted, and the cell mixture gently mixed (for example, by using a 1 ml pipette). Fusion was induced with PEG/DMSO (polyethylene glycol/dimethyl sulfoxide; obtained from Sigma-Aldrich, St. Louis Mo.; 1 ml per million of lymphocytes). PEG/DMSO was slowly added with gentle agitation over one minute followed, by one minute of mixing. IDMEM (DMEM without glutamine; 2 ml per million of B cells), was then added over 2 minutes with gentle agitation, followed by additional IDMEM (8 ml per million B-cells) which was added over 3 minutes.
• The fused cells were pelleted (400×g 6 minutes) and resuspended in 20 ml Selection media (for example, DMEM containing Azaserine and Hypoxanthine [HA] and other supplemental materials as necessary) per million B-cells. Cells were incubated for 20-30 minutes at 37° C. and then resuspended in 200 ml selection media and cultured for three to four days in T175 flasks prior to 96 well plating.
• Cells were distributed into 96-well plates using standard techniques to maximize clonality of the resulting colonies. An alternative method was also employed and the fused cells were directly plated clonally into 384-well plates to ensure monoclonality from the start. After several days of culture, supernatants were collected and subjected to screening assays as detailed in the examples below, including confirmation of binding to human FGF21 receptor, specificity and/or cross-species reactivity. Positive cells were further selected and subjected to standard cloning and subcloning techniques. Clonal lines were expanded in vitro, and the secreted human antibodies obtained for analysis.
• In this manner, mice were immunized with cells expressing full length FGF21R cells mixed with FGF21, or cells expressing a truncated FGFR1c and full length β-Klotho, with a range of 11-17 immunizations over a period of approximately one to three and one-half months. Several cell lines secreting FGF21R-specific antibodies were obtained, and the antibodies were further characterized. The sequences thereof are presented herein and in the Sequence Listing, and results of various tests using these antibodies are provided.
Example 3 Selection of Binding Antibodies by FMAT
• After 14 days of culture, hybridoma supernatants were screened for FGF21R-specific monoclonal antibodies by Fluorometric Microvolume Assay Technology (FMAT) by screening against either the CHO AM1/D/huFGF21R cell line or recombinant HEK293 cells that were transfected with human FGF21R and counter-screening against parental CHO or HEK293 cells. Briefly the cells in Freestyle media (Invitrogen) were seeded into 384-well FMAT plates in a volume of 50 μL/well at a density of 4,000 cells/well for the stable transfectants, and at a density of 16,000 cells/well for the parental cells, and cells were incubated overnight at 37° C. 10 μL/well of supernatant was then added, and the plates were incubated for approximately one hour at 4° C., after which 10 μL/well of anti-human IgG-Cy5 secondary antibody was added at a concentration of 2.8 μg/ml (400 ng/ml final concentration). Plates were then incubated for one hour at 4° C., and fluorescence was read using an FMAT Cellular Detection System (Applied Biosystems).
• In total, over 1,500 hybridoma supernatants were identified as binding to the FGF21 receptor expressing cells but not to parental cells by the FMAT method. These supernatants were then tested in the FGF21 functional assays as described below.
Example 4 Selection of Antibodies that Induce FGF21-Like Signaling
• Experiments were performed to identify functional antibodies that mimic wild-type FGF21 activity (e.g., the ability to induce FGF21-like signaling) using a suitable FGF21 reporter assay. The disclosed FGF21 reporter assay measures activation of FGFR signaling via a MAPK pathway readout. β-Klotho is a co-receptor for FGF21 signaling, and although it is believed not to have any inherent signaling capability due to its very short cytoplasmic domain, it is required for FGF21 to induce signaling through FGFRs.
Example 4.1 ELK-Luciferase Reporter Assay
• ELK-luciferase assays were performed using a recombinant human 293T kidney cell or CHO cell system. Specifically, the host cells were engineered to over-express β-Klotho and luciferase reporter constructs. The reporter constructs contain sequences encoding GAL4-ELK1 and 5×UAS-Luc, a luciferase reporter driven by a promoter containing five tandem copies of the Gal4 binding site. Activation of the FGF21 receptor complex in these recombinant reporter cell lines induces intracellular signal transduction, which in turn leads to ERK and ELK phosphorylation. Luciferase activity is regulated by the level of phosphorylated ELK, and is used to indirectly monitor and quantify FGF21 activity.
• In one example, CHO cells were transfected sequentially using the Lipofectamine 2000 transfection reagent (Invitrogen) according to the manufacturer's protocol with the receptor constructs expressing β-Klotho, FGFR1c and the reporter plasmids: 5×Gal4-Luciferase (minimal TK promoter with 5×Gal4 binding sites upstream of luciferase) and Gal4-ELK1. Gal4-ELK1 binds to the Gal4 binding sites and activates transcription when it is phosphorylated by ERK. Luciferase transcription, and thereby the corresponding enzymatic activity in this context is regulated by the level of phosphorylated ELK1, and is used to indirectly monitor and quantify FGF21 activity.
• Clone 16 was selected as the FGF21 luciferase reporter cell line based on the optimal assay window of 10-20 fold with native FGF21 exhibiting an EC50 in the single nM range.
• For the assay, the ELK-luciferase reporter cells were plated in 96 well assay plates, and serum starved overnight. FGF21 or test samples were added for 6 hours at 37 degrees. The plates were then allowed to cool to room temperature and the luciferase activity in the cell lysates was measured with Bright-Glo (Promega).
Example 4.2 ERK-Phosphorylation Assay
• Alternative host cell lines specifically L6 (a rat myoblastic cell line) was developed and applied to identify antibodies with FGF21-like signaling activity. The rat L6 cell line is a desirable host cell line for the activity assay because it is known to express minimal levels of endogeneous FGF receptors. The L6 cells do not respond to FGF21 even when transfected with β-Klotho expression vector and therefore provides a cleaner background. (Kurosu et al., (2007) J. Biol. Chem. 282, 26687-26695).
• Human primary preadipocytes isolated from subcutaneous adipose tissues of multiple healthy nondiabetic donors were purchased from Zen-Bio, Inc. The preadipocytes were plated in 24-well plates and differentiated for 18 days into mature adipocytes. After a 3-hour starvation period, adipocytes were treated with different concentrations of test molecules for 10 minutes. Following treatment, the media was aspirated and cells were snap-frozen in liquid nitrogen. Cell lysates were prepared and ERK phosphorylation was measured using the Phospho-ERK1/2(Thr202/Tyr204; Thr185/Tyr187)/Total ERK1/2 Assay Whole Cell Lysate Kit from Meso Scale Discovery.”
• L6 cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cells were transfected with plasmids expressing β-Klotho and individual FGFR using the Lipofectamine 2000 transfection reagent (Invitrogen) according to the manufacturer's protocol.
• Analysis of FGF signaling in L6 cells was performed as described in the literature (Kurosu et al., (2007) J. Biol. Chem. 282, 26687-26695). Cell cultures were collected 10 min after the treatment of FGF21 or test molecules and snap frozen in liquid nitrogen, homogenized in the lysis buffer and ERK phosphorylation was measured using the Phospho-ERK1/2(Thr202/Tyr204; Thr185/Tyr187)/Total ERK1/2 Assay Whole Cell Lysate Kit from Meso Scale Discovery.”
• In addition, the factor-dependent mouse BaF3 cell-based proliferation assay used frequently for cytokine receptors can also be developed and applied.
• Among the hybridoma supernatants tested in the CHO cell (Clone 16) based human FGF21 ELK-luciferase reporter assay, over 140 were identified as positive (>20% of the activity of FGF21) when compared to 20 nM FGF21 as the positive control (FIGS. 3 and 4).
• Antibodies can be purified from the conditioned media of the hybridoma cultures of these positives and tested again in the CHO cell based ELK-luciferase reporter assay to assess the potency of the representative antibodies in the dose-responsive assay and determine the EC50. The activities and potency can be confirmed in the L6 cell based ERK1/2-phosphrylation assay. The EC50 is expected to be consistent to the ELK-luciferase assay in the CHO stable cell line Clone 16.
Example 5 Determining that Induction of FGF21-Like Signaling is Specific to the FGFR/13Klotho Complex
• FGF21 has been reported to signal through multiple receptor complexes including FGFR1c, 2c, 3c, and 4 when paired with β-Klotho. The selectivity of the FGF21 agonistic antibodies can be determined in the rat myoblastic L6 cells transfected with vectors expressing the respective FGFRs and β-Klotho as described in Example 4.2.
• Observed selectivity would be strongly suggestive that the action of these antibodies is β-Klotho-dependent yet it must also involve the FGFR component of the signaling complex. The results are set forth in Table 6 below.

• TABLE 9
  FGFR Selectivity

  Molecule	FGFR1c	FGFR2c	FGFR3c	FGFR4
  Fgf21	+	+	+	−
  FGF19	+	+	+	+
  16H7 D58A	+	−	−	−
  49H12.1	+	−	−	−
  51A8.1	+	−	−	−
  51E5.1	+	−	−	−
  54A1.1	+	−	−	−
  60D7.1	+	−	−	−
  63A10.1	+	−	−	−
  64B10.1	+	−	−	−
  65C3.1	+	−	−	−
  66G2.1	+	−	−	−
  67F5.1	+	−	−	−
  67C10.1	+	−	−	−
  68C8.1	+	−	−	−
  49C8.1	+	−	−	−
  49G3.3	+	−	−	−
  56E7.3	+	−	−	−
  52A8.1	+	−	−	−

Example 5.1 Binding Specificity is Exclusively β-Klotho Dependent
• The binding specificity of the reporter assay positive antibodies in the hybridoma supernatants was determined by FACS using 293T cells transiently transfected to express full length FGFR1c alone, β-Klotho alone or FGFR1c and β-Klotho together. Over 98% (141 out of 143 hybridomas) bind β-Klotho alone whereas none bind FGFR1c alone.
Example 6 Activity in Primary Human Adipocytes
• FGF21 stimulates glucose uptake and lipolysis in cultured adipocytes, and adipocytes are considered to be more physiologically relevant than the recombinant reporter cell system.
• A panel of the antibodies were tested in the human adipocyte assay for Erk-phosphorylation activity as described in Example 4.2 and compared with FGF21 for their EC50. The results are set forth below in Table 10 below.

• TABLE 10
  Activity of Antibodies on pERK Human Adipocyte Assay

  	Molecule	EC50

  	Fgf21	0.623
  	16H7	0.280
  	49H12.1	0.254
  	51A8.1	0.213
  	51E5.1	3.221
  	54A1.1	0.206
  	60D7.1	0.496
  	63A10.1	0.435
  	64B10.1	0.955
  	65C3.1	6.387
  	66G2.1	3.529
  	67F5.1	1.438
  	67C10.1	5.789
  	68C8.1	1.216
  	49C8.1	0.243
  	49G3.3	1.424
  	56E7.3	0.916
  	58C2.1	0.317

Example 7 Competition Binding and Epitope Binning
• To compare the similarity of the binding sites of the antibodies on the FGF21 receptor, a series of competition binding experiments can be performed and measured by Biacore. In one example, representative agonistic FGF21 receptor antibodies (and any controls) can be immobilized on the sensor chip surface. Soluble human FGFR1c/β-Klotho ECD-Fc complex or β-Klotho can then be captured on the immobilized antibody surfaces. Finally, several of the test FGF21 receptor antibodies can be injected individually over the captured soluble human FGF21 receptor or β-Klotho. If the injected antibody recognizes a distinct binding site relative to that recognized by the immobilized antibody, a second binding event will be observed. If the antibodies recognize very similar binding site, no more binding will be observed.
• Alternatively or additionally, a Biacore analysis can be carried out with biotinylated-FGF21 immobilized on the sensor ship. 10 nM soluble β-Klotho is then passed over the chip alone or mixed with the individual test antibodies at 100 nM. The results are set forth below in Table 11 below.

• TABLE 11
  Epitope Binning Summary

  Bin 1:	2 nd Campaign - 24H11, 17C3, 16H7, 20D4, 21B4, 22H5, 23F8,
  	21H2, 18B11;
  	3 rd Campaign - 40D2, 46D11
  	Current - 49H12, 51A8, 54A1, 60D7, 49C8, 49G3, 56E7,
  	63A10, 64B10 (64B10.1), 67C8, 68C8.1
  Bin 2:	2 nd Campaign - 17D8, 12C11, 26H11, 12E4, 18G1;
  	3 rd Campaign - 37D3
  Bin 3:	3 rd Campaign - 39F7, 38F2, 39F11, 39G5
  Bin 4:	3 rd Campaign - 20E8
  Bin 5:	current - 51E5
  Bin 6:	current - 52A8 (52A8.1), 67F5 (67F5.1), 67C10 (67C10.1),
  	65C3.1, 66G2.1
  Bold samples in bold are recombinant mAbs
  Italicized samples are from hybridoma supernatants.

Example 8 Recognition of Native and Denatured Structures
• The ability of disclosed antigen binding proteins to recognize denatured and native structures was investigated. The procedure and results were as follows.
Example 8.1 FGF21 Receptor Agonistic Antibodies do not Recognize Denatured Structures
• Cell lysates from CHO cells stably expressing FGF21 receptor (FGFR1c and β-Klotho) or CHO parental cells were diluted with sample buffer without beta-mercaptoethanol (non-reducing conditions). 20 μl of cell lysate were loaded per lane on adjacent lanes separated with a molecular weight marker lane on 4-20% SDS-PAGE gels. Following electrophoresis, the gels were blotted onto 0.2μ nitrocellulose filters. The blots were treated with Tris-buffered saline/Triton-X (TBST) plus 5% non-fat milk (blocking buffer) for 30 minutes. The blots were then cut along the molecular weight marker lanes. The strips were probed with commercial goat anti-murine βKlotho or mouse anti-huFGFR1 (R&D Diagnostics) in TBST/5% milk. Blots were incubated with the antibodies for one hour at room temperature, followed by three washes with TBST+1% milk. The blots were then probed with anti-human or anti-goat IgG-HRP secondary antibodies for 20 min. Blots were given three 15 minute washes with TBST followed by treatment with Pierce Supersignal West Dura developing reagent (1 minute) and exposure to Kodak Biomax X-ray film.
• The commercial anti-β-Klotho and anti-FGFR1 antibodies detected the corresponding receptor proteins in the SDS-PAGE indicating they bind to denatured receptor proteins.
Example 8.2
• FGF21 Receptor Agonistic Antibodies Bind to Native Receptor Structure
• A FACS binding assay was performed with several commercially available FGFR1c and β-Klotho antibodies, and several of the disclosed FGF21 receptor agonistic antibodies. The experiments were performed as follows.
• CHO cells stably expressing FGF21 receptor were treated with R&D Systems mouse anti-huFGFR1, goat anti-mu β-Klotho (1 μg per 1×10⁶ cells in 100 μl PBS/0.5% BSA). Cells were incubated with the antibodies at 4° C. followed by two washes with PBS/BSA. Cells were then treated with FITC-labeled secondary antibodies at 4° C. followed by two washes. The cells were resuspended in 1 ml PBS/BSA and antibody binding was analyzed using a FACSCalibur™ instrument.
• None of the commercial anti-β-Klotho or anti-FGFR1 antibodies tested bind well to cell surface FGF21 receptor, as determined by FACS. This observation further confirmed that the commercial antibodies to the receptor components bind to denatured and non-native structure whereas all of the agonistic antibodies described herein bind receptors on cell surface as shown by FACS or FMAT which were the initial screens.
Example 9 Arginine Scanning
• As described above, antigen binding proteins that bind a complex comprising b-Klotho and one of FGFR1c, FGFR2c and FGFR3c can be created and characterized. To determine the neutralizing determinants on human FGFR1c and/or β-Klotho that these various antigen binding proteins bound, a number of mutant FGFR1c and/or β-Klotho proteins can be constructed having arginine substitutions at select amino acid residues of human FGFR1c and/or β-Klotho. Arginine scanning is an art-recognized method of evaluating where antibodies, or other proteins, bind to another protein, see, e.g., Nanevicz et al., (1995) J. Biol. Chem., 270:37, 21619-25 and Zupnick et al., (2006) J. Biol. Chem., 281:29, 20464-73. In general, the arginine sidechain is positively charged and relatively bulky as compared to other amino acids, which can disrupt antibody binding to a region of the antigen where the mutation is introduced. Arginine scanning is a method that determines if a residue is part of a neutralizing determinant and/or an epitope.
• Various amino acids distributed throughout the human FGFR1c and/or β-Klotho extracellular domains can be selected for mutation to arginine. The selection can be biased towards charged or polar amino acids to maximize the possibility of the residue being on the surface and reduce the likelihood of the mutation resulting in misfolded protein. Using standard techniques known in the art, sense and anti-sense oligonucleotides containing the mutated residues can be designed based on criteria provided by Stratagene Quickchange® II protocol kit (Stratagene/Agilent, Santa Clara, Calif.). Mutagenesis of the wild-type (WT) FGFR1c and/or β-Klotho sequences can be performed using a Quickchange® II kit (Stratagene). Chimeric constructs can be engineered to encode a FLAG-histidine tag (six histidines (SEQ ID NO: 1830)) on the carboxy terminus of the extracellular domain to facilitate purification via the poly-His tag.
• Multiplex analysis using the Bio-Plex Workstation and software (BioRad, Hercules, Calif.) can be performed to determine neutralizing determinants on human FGFR1c and/or β-Klotho by analyzing exemplary human FGFR1c and/or β-Klotho mAbs differential binding to arginine mutants versus wild-type FGFR1c and/or β-Klotho proteins. Any number of bead codes of pentaHis-coated beads (“penta-His” disclosed as SEQ ID NO: 1831) (Qiagen, Valencia, Calif.) can be used to capture histidine-tagged protein. The bead codes can allow the multiplexing of FGFR1c and/or β-Klotho arginine mutants and wild-type human FGFR1c and/or β-Klotho.
• To prepare the beads, 100 ul of wild-type FGFR1c and/or β-Klotho and FGFR1c and/or β-Klotho arginine mutant supernatants from transient expression culture are bound to penta-His-coated beads (“penta-His” disclosed as SEQ ID NO: 1831) overnight at 4° C. or 2 hours at room temperature with vigorous shaking. The beads are then washed as per the manufacturer's protocol and the bead set pooled and aliquoted into 2 or 3 columns of a 96-well filter plate (Millipore, Billerica, Mass., product #MSBVN1250) for duplicate or triplicate assay points, respectively. 100 μl anti-FGFR1c and/or anti-β-Klotho antibodies in 4-fold dilutions are added to the wells, incubated for 1 hour at room temperature, and washed. 100 μl of a 1:100 dilution of PE-conjugated anti-human IgG Fc (Jackson Labs., Bar Harbor, Me.) is added to each well, incubated for 1 hour at room temperature and washed. Beads are resuspended in 1% BSA, shaken for 3 minutes, and read on the Bio-Plex workstation. Antibody binding to FGFR1c and/or β-Klotho arginine mutant protein is compared to antibody binding to the human FGFR1c and/or β-Klotho wild-type from the same pool. A titration of antibody over approximately a 5 log scale can be performed. Median Fluorescence Intensity (MFI) of FGFR1c and/or β-Klotho arginine mutant proteins can be graphed as a percent of maximum wild-type human FGFR1c and/or β-Klotho signal. Those mutants for which signal from all the antibodies are below a cut-off value, e.g., 30% of wild-type FGFR1c and/or β-Klotho can be deemed to be either of too low a protein concentration on the bead due to poor expression in the transient culture or possibly misfolded and can be excluded from analysis. Mutations (i.e., arginine substitutions) that increase the EC50 for the FGFR1c and/or β-Klotho mAb by a cut-off value, e.g., 3-fold or greater (as calculated by, e.g., GraphPad Prism®) can be considered to have negatively affected FGFR1c and/or β-Klotho mAb binding. Through these methods, neutralizing determinants and epitopes for various FGFR1c and/or β-Klotho antibodies are elucidated.
Example 10 Protease Protection Analysis
• Regions of the human FGF21 receptor bound by the antigen binding proteins that bind human FGF21 receptor, e.g., FGFR1c, β-Klotho or FGFR1c and β-Klotho complex can be identified by fragmenting human FGF21 receptor into peptides with specific proteases, e.g., AspN, Lys-C, chymotrypsin or trypsin. The sequence of the resulting human FGF21 receptor peptides (i.e., both disulfide- and non-disulfide-containing peptide fragments from FGFR1c and β-Klotho portions) can then be determined. In one example, soluble forms of a human FGF21 receptor, e.g., a complex comprising the FGFR1c ECD-Fc and β-Klotho ECD-Fc heterodimer described herein can be digested with AspN (which cleaves after aspartic acid and some glutamic acid residues at the amino end) by incubating about 100 μg of soluble FGF21 receptor at 1.0 mg/ml in 0.1M sodium phosphate (pH 6.5) for 20 hrs at 37° C. with 2 μg of AspN.
• A peptide profile of the AspN digests can then be generated on HPLC chromatography while a control digestion with a similar amount of antibody is expected to be essentially resistant to AspN endoprotease. A protease protection assay can then be performed to determine the proteolytic digestion of human FGF21 receptor in the presence of the antigen binding proteins. The general principle of this assay is that binding of an antigen binding protein to the FGF21 receptor can result in protection of certain specific protease cleavage sites and this information can be used to determine the region or portion of FGF21 receptor where the antigen binding protein binds.
• Briefly, the peptide digests can be subjected to HPLC peptide mapping; the individual peaks are collected, and the peptides are identified and mapped by on-line electrospray ionization LC-MS (ESI-LC-MS) analyses and/or by N-terminal sequencing. HPLC analyses for these studies can be performed using a narrow bore reverse-phase C18 column (Agilent Technologies) for off-line analysis and using a capillary reverse phase C18 column (The Separation Group) for LC-MS. HPLC peptide mapping can be performed with a linear gradient from 0.05% trifluoroacetic acid (mobile phase A) to 90% acetonitrile in 0.05% trifluoroacetic acid. Columns can be developed at desirable flow rate for narrow bore HPLC for off-line or on-line LC-MS analyses, and for capillary HPLC for on-line LC-MS analyses.
• Sequence analyses can be conducted by on-line LC-MS/MS and by Edman sequencing on the peptide peaks recovered from HPLC. On-line ESI LC-MS analyses of the peptide digest can be performed to determine the precise mass and sequence of the peptides that are separated by HPLC. The identities of selected peptides present in the peptide peaks from the protease digestion can thus be determined.
Example 11 Construction of Chimeric Receptors
• An additional method of determining activation determinants on which these various antigen binding proteins bind is as follows. Specific chimeric FGFR1c and/or β-Klotho proteins between human and mouse species can be constructed, expressed in transient or stable 293 or CHO cells (as described herein) and tested. For example, a chimeric FGF21 receptor can be constructed comprising native human FGFR1c, FGFR2c, FGFR3c or FGFR4 receptors. By way of example, FGFR1c can be paired with chimeric human/mouse β-Klotho in which selected regions or sequences on the human β-Klotho are systematically replaced by the corresponding mouse-specific residues (see, e.g., FIG. 2A-2C). Similarly, native human β-Klotho can be paired with chimeric human/mouse FGFR1c, FGFR2c, FGFR3c or FGFR4. Here, selected regions or sequences on the human FGFR1c are systematically replaced by the corresponding mouse-specific residues (see, e.g., the alignments of FIGS. 1A-1B). The critical sequences involved in the binding and/or activity of the antigen binding proteins can be derived through binding assay or activity measurements described in previous Examples 4, 5, 6, and 7 based on the chimeric FGF21 receptors.
Example 11.1 Construction of Specific Chimeras
• Human-mouse β-Klotho chimeras were constructed using the methodology described above. A schematic of the chimeras constructed is presented in FIG. 4. In summary, the chimeras generated comprised (from N- to C-terminus) a fusion of a human β-Klotho sequence fused to a murine β-Klotho sequence fused to a human β-Klotho sequence. Human β-Klotho Klotho (SEQ ID NO: 7) was used as a framework into which regions of murine β-Klotho (full length sequence shown in SEQ ID NO:468) were inserted. The regions of murine β-Klotho that were inserted were as follows:

• Murine Residues 82P-520P

  (amino acids 82 to 520 of SEQ ID NO: 10)

  PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSY

  IFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDS

  LVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGD

  RVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVW

  HNYDKNFRPHQKGWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFA

  NPIHGDGDYPEFMKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSN

  TVVKMGQNVSLNLRQVLNWIKLEYDDPQILISENGWFTDSYIKTEDTTAI

  YMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDF

  NSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDMKGRFP

  Murine Residues 506F-1043S

  (amino acids 506 to 1043 of SEQ ID NO: 10)

  FPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTG

  NRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSIL

  PTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLS

  SGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDMYNRTSND

  TYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPANPFVDSH

  WKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSVLPRFT

  AKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQDITRLS

  SPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQIRKYYL

  EKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAKSSVQF

  YSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFFGCCFIST

  LAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS

  Murine Residues 1M-193L

  (amino acids 506 to 1043 of SEQ NO: 10)

  MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAV

  TGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQVEGSW

  KTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQ

  FSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTL

  Murine Residues 82P-302S

  (amino acids 82 to 302 of SEQ ID NO: 10)

  PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSY

  IFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDS

  LVLRNIEPIVTLYHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGD

  RVKYWITIHNPYLVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVW

  HNYDKNFRPHQKGWLSITLGS

  Murine Residues 194Y-416G

  (amino acids 194 to 416 of SEQ ID NO: 10)

  YHWDLPLTLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPY

  LVAWHGFGTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQK

  GWLSITLGSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEF

  MKTGAMIPEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLN

  LRQVLNWIKLEYDDPQILISENG

  Murine Residues 302S-506F

  (amino acids 302 to 506 of SEQ ID NO: 10)

  SHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMIP

  EFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNWI

  KLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIR

  VFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQII

  QDNGF

  Murine Residues 416G-519P

  (amino acids 416 to 519 of SEQ ID NO: 10)

  GWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEIRVFGYTAWTLLDGFE

  WQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQIIQDNGFPLKESTPDM

  KGRF

  Murine Residues 507P-632G

  (amino acids 507 to 632 of SEQ NO: 10)

  PLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGN

  RLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILP

  TGNLSKVNRQVLRYYRCVVSEGLKLG

  Murine Residues 520P-735A

  (amino acids 520 to 735 of SEQ ID NO: 10)

  PCDFSWGVTESVLKPEFTVSSPQFTDPHLYVWNVTGNRLLYRVEGVRLKT

  RPSQCTDYVSIKKRVEMLAKMKVTHYQFALDWTSILPTGNLSKVNRQVLR

  YYRCVVSEGLKLGVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQ

  DYAELCFRELGDLVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQ

  VWHLYDRQYRPVQHGA

  Murine Residues 632G-849Q

  (amino acids 632 to 849 of SEQ ID NO: 10)

  GVFPMVTLYHPTHSHLGLPLPLLSSGGWLNMNTAKAFQDYAELCFRELGD

  LVKLWITINEPNRLSDMYNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPV

  QHGAVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYP

  SVMKEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIH

  KQLNTNRSVADRDVQFLQ

  Murine Residues 735A-963S

  (amino acids 735 to 963 of SEQ ID NO: 10)

  AVSLSLHCDWAEPANPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVM

  KEYIASKNQRGLSSSVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQL

  NTNRSVADRDVQFLQDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIY

  ITANGIDDLALEDDQIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEE

  KSKPRFGFFTSDFRAKSSVQFYSKLISSS

  Murine Residues 1M-81F

  (amino acids 1 to 81 of SEQ ID NO: 10)

  MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAV

  TGFSGDGKAIWDKKQYVSPVNPSQLFLYDTF

  Murine Residues 82P-193L

  (amino acids 82 to 193 of SEQ ID NO: 10)

  PKNFSWGVGTGAFQVEGSWKTDGRGPSIWDRYVYSHLRGVNGTDRSTDSY

  IFLEKDLLALDFLGVSFYQFSISWPRLFPNGTVAAVNAQGLRYYRALLDS

  LVLRNIEPIVTL

• The chimeras that were generated using the murine β-Klotho sequences comprised the following:

• TABLE 12
  			N-terminal		C-terminal
  		SEQ.	Human β-	Mouse β-	Human β-
  Con-	Construct	ID	Klotho	Klotho	Klotho
  struct	Identifier	NO.	Residues	Residues	Residues

  1	huBeta_Klotho (1-		1-81	82-520	523-1044
  	81, 523-1044)
  	(muBetaKLOTHO
  	82-520)
  2	huBeta_Klotho (1-		1-507	506-1043
  	507)
  	(muBetaKLOTHO
  	506F-1045S)
  3	huBeta_Klotho			1-193	194-1044
  	(194-1044)
  	(muBetaKLOTHO
  	1-L193)
  4	huBeta_Klotho (1-		1-81	82-302	303-1044
  	81, 303-1044)
  	(muBetaKLOTHO
  	82P-302S)
  5	huBeta_Klotho (1-		1-193	194-416	419-1044
  	193, 419-1044)
  	(muBetaKLOTHO
  	Y194-416G)
  6	huBeta_Klotho(1-		1-301	302-506	509-1044
  	301, 509-1044)
  	(muBetaKLOTHO
  	S302-F506)
  7	huBeta_Klotho(1-		1-417	416-519	522-1044
  	417, 522-1044)
  	(muBetaKLOTHO
  	G416-F519)
  8	huBeta_Klotho (1-		1-508	507-632	635-1044
  	507, 635-1044)
  	(muBeta KLOTHO
  	F06-G632)
  9	huBeta_Klotho (1-		1-521	520-735	738-1044
  	521, 738-1044)
  	(muBeta KLOTHO
  	520P-735A)
  10	huBeta_Klotho (1-		1-633	632-849	852-1044
  	633, 852-1044)
  	(muBeta KLOTHO
  	632G-849Q)
  11	huBeta_Klotho (1-		1-736	735-963	967-1044
  	736, 967-1044)
  	(muBeta KLOTHO
  	735A-963S)
  12	huBeta_Klotho			1-81	82-1044
  	(82-1044) (muBeta
  	KLOTHO 1-81F)
  13	huBeta_Klotho (1-		1-81	82-193	194-1044
  	81, 194-1044)
  	(muBeta KLOTHO
  	82P-193L)
  14	huBeta_Klotho (1-		1-301	302-506,	967-1044
  	301, 509-743, 967-			742-964
  	1044) (muBeta
  	KLOTHO 302-
  	506, 742-964)

  
  The generated chimeras comprised the following amino acid sequences:

• (i) huBeta_Klotho(1-81, 523-1044)(muBetaKLOTHO

  82-520)

  (SEQ ID NO: 1898)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSW

  KTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQ

  FSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPL

  TLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGF

  GTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITL

  GSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMI

  PEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNW

  IKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEI

  RVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQI

  IQDNGFPLKESTPDMKGRFPCDFSWGVTESVLKPESVASSPQFSDPHLYV

  WNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALD

  WASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLP

  EPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYN

  RSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANP

  YADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSA

  LPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQD

  ITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRL

  RKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAK

  SSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGC

  CFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (ii) huBeta_Klotho(1-507)(muBetaKLOTHO 506F-1045S)

  (SEQ ID NO: 1899)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHL

  YVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFA

  LDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLG

  LPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDM

  YNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPA

  NPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSS

  SVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFL

  QDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDD

  QIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFR

  AKSSVQFYSKLISSSGLPAENRSPACGQPAEDTDCTICSFLVEKKPLIFF

  GCCFISTLAVLLSITVFHHQKRRKFQKARNLQNIPLKKGHSRVFS

  (iii) huBeta_Klotho(194-1044)(muBetaKLOTHO 1-L193)

  (SEQ ID NO: 1900)

  MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAV

  TGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFSWGVGTGAFQVEGSW

  KTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQ

  FSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (iv) huBeta_Klotho(1-81, 303-1044)(muBetaKLOTHO

  82P-302S)

  (SEQ ID NO: 1901)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSW

  KTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQ

  FSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPL

  TLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGF

  GTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (v) huBeta_Klotho(1-193, 419-1044)(muBetaKLOTHO

  Y194-416G)

  (SEQ ID NO: 1902)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  TLQEEYGGWKNATMIDLFNDYATYCFQTFGDRVKYWITIHNPYLVAWHGF

  GTGMHAPGEKGNLTAVYTVGHNLIKAHSKVWHNYDKNFRPHQKGWLSITL

  GSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMI

  PEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNW

  IKLEYDDPQILISENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLDEI

  RVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYKQI

  IRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYV

  WNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALD

  WASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLP

  EPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYN

  RSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANP

  YADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSA

  LPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQD

  ITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRL

  RKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAK

  SSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGC

  CFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (vi) huBeta_Klotho(1-301, 509-1044)(muBetaKLOTHO

  S302-F506)

  (SEQ ID NO: 1903)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMI

  PEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNW

  IKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEI

  RVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQI

  IQDNGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYV

  WNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALD

  WASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLP

  EPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYN

  RSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPANP

  YADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSSSA

  LPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFLQD

  ITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDDRL

  RKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFKAK

  SSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGC

  CFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (vii) huBeta_Klotho(1-417, 522-1044)(muBetaKLOTHO

  G416-F519)

  (SEQ ID NO: 1904)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFD

  EIRVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYK

  QIIQDNGFPLKESTPDMKGRFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (viii) huBeta_Klotho(1-507, 635-1044)(muBeta KLOTHO

  F06-G632)

  (SEQ ID NO: 1905)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFPLKESTPDMKGRFPCDFSWGVTESVLKPEFTVSSPQFTDPHL

  YVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFA

  LDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (ix) huBeta_Klotho(1-521, 738-1044)(muBeta KLOTHO

  520P-735A)

  (SEQ ID NO: 1906)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPEFTVSSPQFTDPHL

  YVWNVTGNRLLYRVEGVRLKTRPSQCTDYVSIKKRVEMLAKMKVTHYQFA

  LDWTSILPTGNLSKVNRQVLRYYRCVVSEGLKLGVFPMVTLYHPTHSHLG

  LPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDM

  YNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (x) huBeta_Klotho(1-633, 852-1044)(muBeta KLOTHO

  632G-849Q)

  (SEQ ID NO: 1907)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGVFPMVTLYHPTHSHLG

  LPLPLLSSGGWLNMNTAKAFQDYAELCFRELGDLVKLWITINEPNRLSDM

  YNRTSNDTYRAAHNLMIAHAQVWHLYDRQYRPVQHGAVSLSLHCDWAEPA

  NPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSS

  SVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (xi) huBeta_Klotho(1-736, 967-1044)(muBeta KLOTHO

  735A-963S)

  (SEQ ID NO: 1908)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHCDWAEPA

  NPFVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSS

  SVLPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFL

  QDITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDD

  QIRKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFR

  AKSSVQFYSKLISSSGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (xii) huBeta_Klotho(82-1044)(muBeta KLOTHO 1-81F)

  (SEQ ID NO: 1909)

  MKTGCAAGSPGNEWIFFSSDERNTRSRKTMSNRALQRSAVLSAFVLLRAV

  TGFSGDGKAIWDKKQYVSPVNPSQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (xiii) huBeta_Klotho(1-81, 194-1044)(muBeta KLOTHO

  82P-193L)

  (SEQ ID NO: 1910)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFSWGVGTGAFQVEGSW

  KTDGRGPSIWDRYVYSHLRGVNGTDRSTDSYIFLEKDLLALDFLGVSFYQ

  FSISWPRLFPNGTVAAVNAQGLRYYRALLDSLVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRSENTMDIFKCQQSMVSVLGWFANPIHGDGDYPEGMRKKLFS

  VLPIFSEAEKHEMRGTADFFAFSFGPNNFKPLNTMAKMGQNVSLNLREAL

  NWIKLEYNNPRILIAENGWFTDSRVKTEDTTAIYMMKNFLSQVLQAIRLD

  EIRVFGYTAWSLLDGFEWQDAYTIRRGLFYVDFNSKQKERKPKSSAHYYK

  QIIRENGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHL

  YVWNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFA

  LDWASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLG

  LPEPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDI

  YNRSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHADWAEPA

  NPYADSHWRAAERFLQFEIAWFAEPLFKTGDYPAAMREYIASKHRRGLSS

  SALPRLTEAERRLLKGTVDFCALNHFTTRFVMHEQLAGSRYDSDRDIQFL

  QDITRLSSPTRLAVIPWGVRKLLRWVRRNYGDMDIYITASGIDDQALEDD

  RLRKYYLGKYLQEVLKAYLIDKVRIKGYYAFKLAEEKSKPRFGFFTSDFK

  AKSSIQFYNKVISSRGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFL

  GCCFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

  (xiv) huBeta_Klotho (1-301, 509-743, 967-1044)

  (muBetaKLOTHO 302-506, 742-964)

  (SEQ ID NO: 1911)

  MKPGCAAGSPGNEWIFFSTDEITTRYRNTMSNGGLQRSVILSALILLRAV

  TGFSGDGRAIWSKNPNFTPVNESQLFLYDTFPKNFFWGIGTGALQVEGSW

  KKDGKGPSIWDHFIHTHLKNVSSTNGSSDSYIFLEKDLSALDFIGVSFYQ

  FSISWPRLFPDGIVTVANAKGLQYYSTLLDALVLRNIEPIVTLYHWDLPL

  ALQEKYGGWKNDTIIDIFNDYATYCFQMFGDRVKYWITIHNPYLVAWHGY

  GTGMHAPGEKGNLAAVYTVGHNLIKAHSKVWHNYNTHFRPHQKGWLSITL

  GSHWIEPNRTDNMEDVINCQHSMSSVLGWFANPIHGDGDYPEFMKTGAMI

  PEFSEAEKEEVRGTADFFAFSFGPNNFRPSNTVVKMGQNVSLNLRQVLNW

  IKLEYDDPQILISENGWFTDSYIKTEDTTAIYMMKNFLNQVLQAIKFDEI

  RVFGYTAWTLLDGFEWQDAYTTRRGLFYVDFNSEQKERKPKSSAHYYKQI

  IQDNGFSLKESTPDVQGQFPCDFSWGVTESVLKPESVASSPQFSDPHLYV

  WNATGNRLLHRVEGVRLKTRPAQCTDFVNIKKQLEMLARMKVTHYRFALD

  WASVLPTGNLSAVNRQALRYYRCVVSEGLKLGISAMVTLYYPTHAHLGLP

  EPLLHADGWLNPSTAEAFQAYAGLCFQELGDLVKLWITINEPNRLSDIYN

  RSGNDTYGAAHNLLVAHALAWRLYDQQFRPSQRGAVSLSLHCDWAEPANP

  FVDSHWKAAERFLQFEIAWFADPLFKTGDYPSVMKEYIASKNQRGLSSSV

  LPRFTAKESRLVKGTVDFYALNHFTTRFVIHKQLNTNRSVADRDVQFLQD

  ITRLSSPSRLAVTPWGVRKLLAWIRRNYRDRDIYITANGIDDLALEDDQI

  RKYYLEKYVQEALKAYLIDKVKIKGYYAFKLTEEKSKPRFGFFTSDFRAK

  SSVQFYSKLISSSGFPFENSSSRCSQTQENTECTVCLFLVQKKPLIFLGC

  CFFSTLVLLLSIAIFQRQKRRKFWKAKNLQHIPLKKGKRVVS

• Various antigen binding proteins provided herein, as well as human FGF21, were tested for the ability to activate chimeras in L6 cells. FIG. 5 shows the observed results with each tested molecule.
• These data indicate that while human FGF21 was able to activate FGFR1c combined with all of the human/mouse β-Klotho chimeras (the “+” sign indicates activity on the receptor), the substitutions of mouse sequences into human β-Klotho affected the activities of 16H7, 37D3, and 39F7 (See FIG. 5). These results suggest that β-Klotho sequences 1-81, 302-522, and 849-1044 are important for the activities of agonistic antigen binding proteins and may represent an important epitope for their function.
• In addition, various antigen binding proteins were also tested for binding to the various human/mouse β-Klotho chimeras transiently expressed on the surface of HEK-293T cells by flow cytometry. Transfection and flow-cytometry was performed as described in Example 12. It will be appreciated that antibodies which do not have the ability to cross-bind full length murine β-Klotho are unable to bind the human/mouse β-Klotho chimera if the chimera spans a region of the antibody's binding site. In this manner, the binding profile of each antibody on the panel of chimeras reveals epitope information for the antibody. Data is shown below in Table 10. The anti-β-Klotho antibody 2G10 (which binds both human and mouse β-Klotho) was used as the positive control for expression of each human/mouse chimera. Using this positive control it was determine the expression level of chimeras 7 and 8 were not high enough to provide robust data and therefore they were eliminated from the analysis. One antibody, 26H11, was found to bind to full-length mouse β-Klotho and therefore could not be assigned an epitope in this analysis. Other antibodies which did not cross-bind to mouse β-Klotho could be group into epitope clusters. The first cluster included antibodies 16H7, 46D11, and 49G3.3, which antibodies did not bind to chimera #3 and chimera #12, indicating that the epitope includes the 1-81 region. Additionally, this group of antibodies also lacked observed binding to chimeras 1, 5, 6 and 14, which indicates that the epitope also includes the 294-506 region. Taken together, this data suggests that these antibodies have a complex non-linear type of epitope.
• A second cluster included only antibody 65C3.1. This antibody lacked binding to chimeras #2, #11, and #14, indicating an epitope in the region of 849-936. A third cluster, including antibodies 49H12.1, 54A1.1, 49C8.1, 51A8.1, 63A10.1, 64B10.1, 68C8.1 and 39F7, lacked binding to chimera #1, #5, and #6, indicating that their epitope is in the 302-416 region. The forth cluster included antibodies 67C10.1, 51E5.1, 52A8.1, 66G2, 167F5.1, which lacked binding on chimeras #2, #8, #9, #10, #11, and #14 indicating that the epitope for these antibodies lies within region 506-1045. A “+” or “−” symbol in the chart below indicates binding of the respective antibody (“+”), or lack of binding (“−”) to the chimera and/or the respective ortholog of β-Klotho, or Mock Cells (negative control).

• TABLE 13
  Chimera Binding

  			Mock
  			cells
  CHIMERA #	hu β-	mu β-	(Neg.	Epitope

  	1	2	3	4	5	6	9	10	11	12	13	14	Klotho	klotho	Cont.)	Region

  2G10

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  −

  26H11

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  +

  −

  16H7

  −

  +

  −

  +

  −

  −

  +

  +

  +

  −

  +

  −

  +

  −

  −

  1-81 &

  49G3.3

  −

  +

  −

  +

  −

  −

  +

  +

  +

  −

  +

  −

  +

  −

  −

  302-416

  46D11

  −

  +

  −

  +

  −

  −

  +

  +

  +

  −

  +

  −

  +

  −

  −

  49H12.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  302-416

  54A1.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  49C8.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  51A8.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  63A10.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  64B10.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  68C8.1

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  39F7

  −

  +

  +

  +

  −

  −

  +

  +

  +

  +

  +

  −

  +

  −

  −

  65C3.1

  +

  −

  +

  +

  +

  +

  +

  +

  −

  +

  +

  −

  +

  −

  −

  849-936

  67C10.1

  +

  −

  +

  +

  +

  +

  −

  −

  −

  +

  +

  −

  +

  −

  −

  506-1045

  51E5.1

  +

  −

  +

  +

  +

  +

  −

  −

  −

  +

  +

  −

  +

  −

  −

  52A8.1

  +

  −

  +

  +

  +

  +

  −

  −

  −

  +

  +

  −

  +

  −

  −

  66G2.1

  +

  −

  +

  +

  +

  +

  −

  −

  −

  +

  +

  −

  +

  −

  −

  67F5.1

  +

  −

  +

  +

  +

  +

  −

  −

  −

  +

  +

  −

  +

  −

  −

  IgG2/K

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  Control

  IgG4/K

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  Control

  Secondary

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  −

  Only

Example 12 FGF21 Receptor Agonistic Antibodies Binding Selectivity
• A panel of FGF21 receptor agonistic antibodies were assayed using flow cytometry for the binding to human FGFR1/human β-klotho transiently co-transfected HEK293T cells, human FGFR1c transiently transfected HEK293T cells and β-klotho transiently transfected HEK293T cells. In addition, binding was also tested on HEK-293T cells transiently transfected with cynomologous monkey orthologs of FGFR1c and β-klotho. Cells were transfected by preparing bug plasmid DNA in 500 ul OptiMEM™ media (Invitrogen™) and mixing this with 10 ul of 293fectin™ in 500 ul OptiMEM™ media, and then incubating the solution for 5 minutes at room temperature. This solution was then added dropwise to 10 million HEK293T cells in 10 ml of media. 24 hours following transfection, the cells were washed and 50,000 cells were stained with each primary antibody, 50 ul of unpurified hybridoma supernatant was diluted 1:2 and used for staining cells. After a one hour incubation at 4° c., the cells were washed and an anti-Human Fc-specific secondary was added. Stained cells were then analyzed on a flow cytometer. The panel of hybridoma supernatants tested all bound specifically to human β-Klotho/human FGFR1c co-transfected cells as well as human β-Klotho transfected alone. Data is shown below in Table 11. No staining was detected for any of the antibodies on cells transfected with FGFR1c alone. All antibodies except 64B10.1 and 68C8.1 specifically detected cynomologous β-Klotho/cynoFGFR1c co-transfected cells.

• TABLE 14
  FGFR Antibody Selectivity

  		Human	Human β-	HuFGFR1c/Hu	Cyno
  	Mock	FGFR1c	Klotho	β-Klotho Co-	FGFR1c/Cyno
  	Transfected	Transfect	Tranfected	transfected	β-Klotho Co-
  	293T cells	293T cells	293T Cells	293T Cells	transfected Cells
  Antibody	GeoMean	GeoMean	GeoMean	GeoMean	GeoMean

  49G3.3	648	706	14891	17919	25947
  49H12.1	581	719	16213	21731	20870
  51E5.1	723	747	16900	20951	36536
  51A8.1	728	795	17799	22826	18476
  54A1.1	709	770	14317	18701	11106
  59G10.3	686	780	15669	21105	33464
  63A10.1	648	834	17442	20432	32558
  64B10.1	624	691	14939	19850	701
  65C3.1	705	719	13720	18835	24564
  66G2.1	695	780	12671	16715	21566
  67F5.1	632	757	13482	13948	15784
  67C10.1	688	780	15114	18896	4063
  68C8.1	592	798	15905	20622	750
  16H7 @	723	869	16335	20686	31319
  5 ug/ml

Example 13 Hotspot/Covariant Mutants
• A total of 17 antibodies were analyzed for potential hotspots and covariance violations. The designed variants (shown below) outline amino acid substitutions capable of reducing and/or avoiding isomerization, deamidation, oxidation, covariance violations, and the like. In the data below, “02 49C8.1_VK: [F21I]” refers to a variant of the parental antibody 49C8.1 that has a mutation at position 21, from F (Phe) to I (Isoleucine). Note that a structure-based numbering scheme is followed for designating amino acid positions. It will be appreciated that these single point mutations can be combined in any combinatorial manner in order to arrive at a final desired molecule. The data are shown below in Table 15 and Table 16.

• TABLE 15
  Antibody 49C8.1

  02	49C8.1_VK: [F21I]
  03	49C8.1_VK: [F91L]
  04	49C8.1_VK: [I101F]
  05	49C8.1_VK: [I101V]
  06	49C8.1_VK: [P141Q]
  07	49C8.1_VK: [P141G]
  08	49C8.1_VH: [T48P]
  09	49C8.1_VH: [N61Q]
  10	49C8.1_VH: [G65T]

  Antibody 49H12_N83D

  01	49H12_N83D_VK: [F91L]
  02	49H12_N83D_VK: [I101F]
  03	49H12_N83D_VK: [I101V]
  04	49H12_N83D_VH: [M24K]
  05	49H12_N83D_VH: [I30T]
  06	49H12_N83D_VH: [T48P]
  07	49H12_N83D_VH: [W57Y]
  08	49H12_N83D_VH: [W111Y]

  Antibody 49G3.3

  01	49G3.3_VK: [F91L]
  02	49G3.3_VK: [I101F]
  03	49G3.3_VK: [I101V]
  04	49G3.3_VK: [G141Q]
  05	49G3.3_VH: [E17Q]
  06	49G3.3_VH: [V25F]
  07	49G3.3_VH: [T56A]
  08	49G3.3_VH: [T56G]
  09	49G3.3_VH: [T144L]
  10	49G3.3_VH: [T144M]

  Antibody 51A8.1

  01	51A8.1_VL: [I98T]
  02	51A8.1_VL: [I98A]
  03	51A8.1_VH: [R17G]
  04	51A8.1_VH: [D61E]
  05	51A8.1_VH: [D72E]
  06	51A8.1_VH: [D110E]

  Antibody 51E5.1

  01	51E5.1_VK: [N53K]
  02	51E5.1_VK: [R54L]
  03	51E5.1_VK: [R54S]
  04	51E5.1_VK: [G141Q]
  05	51E5.1_VH: [D59E]
  06	51E5.1_VH: [H60T]

  Antibody 52A8.1

  01	52A8.1_VK: [F10S]
  02	52A8.1_VK: [H44Y]
  03	52A8.1_VK: [H44F]
  04	52A8.1_VK: [G141Q]
  05	52A8.1_VH: [W57Y]
  06	52A8.1_VH: [R95S]
  07	52A8.1_VH: [W135Y]

  Antibody 54A1.1_N83D

  01	54A1.1_N83D_VK: [A5T]
  02	54A1.1_N83D_VK: [L46Q]
  03	54A1.1_N83D_VK: [G81S]
  04	54A1.1_N83D_VK: [F91L]
  05	54A1.1_N83D_VK: [I101F]
  06	54A1.1_N83D_VK: [I101V]
  07	54A1.1_N83D_VK: [P141G]
  08	54A1.1_N83D_VK: [P141Q]
  09	54A1.1_N83D_VH: [T48P]
  10	54A1.1_N83D_VH: [W57Y]
  11	54A1.1_N83D_VH: [W111Y]

  Antibody 56E7.3

  01	56E7.3_VK: [N53K]
  02	56E7.3_VK: [F91L]
  03	56E7.3_VK: [I101F]
  04	56E7.3_VK: [P141Q]
  05	56E7.3_VK: [P141G]
  06	56E7.3_VK: [T144K]
  07	56E7.3_VK: [T144R]
  08	56E7.3_VH: [L31F]
  09	56E7.3_VH: [D65E]
  10	56E7.3_VH: [T84K]
  11	56E7.3_VH: [R95S]

  Antibody 58C2.1

  01	58C2.1_VK: [D36E]
  02	58C2.1_VH: [R17G]
  03	58C2.1_VH: [D61E]
  04	58C2.1_VH: [D72E]
  05	58C2.1_VH: [N116Q]

  Antibody 60D7.1_N30T

  01	60D7.1_N30T_VK: [D33E]
  02	60D7.1_N30T_VK: [D36E]
  03	60D7.1_N30T_VH: [R17G]
  04	60D7.1_N30T_VH: [D61E]
  05	60D7.1_N30T_VH: [D72E]
  06	60D7.1_N30T_VH: [W115Y]

  Antibody 63A10.1_C58S

  01	63A10.1_C58S_VL: [H9L]
  02	63A10.1_C58S_VL: [H9P]
  03	63A10.1_C58S_VL: [T15L]
  04	63A10.1_C58S_VL: [T15P]
  05	63A10.1_C58S_VL: [A16G]
  06	63A10.1_C58S_VL: [M18T]
  07	63A10.1_C58S_VL: [D51A]
  08	63A10.1_C58S_VL: [D51S]
  09	63A10.1_C58S_VL: [D51F]
  10	63A10.1_C58S_VL: [D67E]
  11	63A10.1_C58S_VL: [P83S]
  12	63A10.1_C58S_VL: [E97Q]
  13	63A10.1_C58S_VL: [D110E]
  14	63A10.1_C58S_VL: [D136E]
  15	63A10.1_C58S_VH: [D11G]
  16	63A10.1_C58S_VH: [K14Q]
  17	63A10.1_C58S_VH: [I29F]
  18	63A10.1_C58S_VH: [G56S]
  19	63A10.1_C58S_VH: [D64E]
  20	63A10.1_C58S_VH: [G84D]
  21	63A10.1_C58S_VH: [G84N]
  22	63A10.1_C58S_VH: [T98A]
  23	63A10.1_C58S_VH: [T107A]
  24	63A10.1_C58S_VH: [T108R]
  25	63A10.1_C58S_VH: [D109E]
  26	63A10.1_C58S_VL: [W109Y]

  Antibody 63A10.3_N20R_C42S

  01	63A10.3_N20R_C42S_VL: [W109Y]
  02	63A10.3_N20R_C42S_VL: [D67E]
  03	63A10.3_N20R_C42S_VL: [D110E]
  04	63A10.3_N20R_C42S_VH: [D11G]
  05	63A10.3_N20R_C42S_VH: [K14Q]
  06	63A10.3_N20R_C42S_VH: [I29F]
  07	63A10.3_N20R_C42S_VH: [G56S]
  08	63A10.3_N20R_C42S_VH: [D64E]
  09	63A10.3_N20R_C42S_VH: [G84N]
  10	63A10.3_N20R_C42S_VH: [T98A]
  11	63A10.3_N20R_C42S_VH: [T107A]
  12	63A10.3_N20R_C42S_VH: [T108R]
  13	63A10.3_N20R_C42S_VH: [D109E]
  14	63A10.3_N20R_C42S_VL: [W109Y]

  Antibody 64B10.1

  01	64B10.1_VL: [G92A]
  02	64B10.1_VL: [G99E]
  03	64B10.1_VL: [D110E]
  04	64B10.1_VH: [L5Q]
  05	64B10.1_VH: [T144L]
  06	64B10.1_VH: [T144M]
  07	64B10.1_VL: [W109Y]
  08	64B10.1_VH: [W113Y]

  Antibody 66G2

  01	66G2_VK: [R54L]
  02	66G2_VK: [K88E]
  03	66G2_VK: [K88D]
  04	66G2_VK: [N110Q]
  05	66G2_VH: [R17G]
  06	66G2_VH: [D61E]
  07	66G2_VH: [D72E]
  08	66G2_VH: [I78F]
  09	66G2_VH: [T108K]
  10	66G2_VH: [T108R]

  Antibody 67F5

  1. 01	67F5_VK: [H57Y]
  2. 02	67F5_VK: [Q97E]
  3. 03	67F5_VK: [S98P]
  4. 04	67F5_VK: [A99E]
  5. 05	67F5_VK: [N105Y]
  6. 06	67F5_VH: [K5Q]
  7. 07	67F5_VK: [W135Y]
  8. 08	67F5_VK: [W137Y]

  Antibody 67C10

  1. 01	67C10_VK: [F2I]
  2. 02	67C10_VK: [D36E]
  3. 03	67C10_VH: [Q24K]
  4. 04	67C10_VH: [D65E]

  Antibody 68C8

  1. 01	68C8_VL: [G92A]
  2. 02	68C8_VL: [G99E]
  3. 03	68C8_VL: [D110E]
  4. 04	68C8_VH: [D29G]
  5. 05	68C8_VH: [H83D]
  6. 06	68C8_VH: [G107A]
  7. 07	68C8_VH: [T144L]
  8. 08	68C8_VH: [T144M]
  9. 09	68C8_VL: [W109Y]
  10. 10	68C8_VH: [W113Y]

• TABLE 16
  Exemplary Substitutions

  >49C8.1 VK

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID

  NO: 1912)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1915)

  >49G3.3 VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3 VH

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1917)

  >51A8.1 VL

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1918)

  >51A8.1 VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1919)

  >51E5.1 VK

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFG

  VPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1920)

  >51E5.1 VH

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1921)

  >52A8.1 VK

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1922)

  >52A8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1923)

  >54A1.1 N83D VK

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1924)

  >54A1.1 N83D VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >56E7.3 VK

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 1926)

  >56E7.3 VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >58C2.1 VK

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 1928)

  >58C2.1 VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWND

  GNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYP

  YYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 1929)

  >60D7.1 N30T VK

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 1930)

  >60D7.1 N30T VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931)

  >63A10.1 C58S VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1 C58S VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.3 N20R C42S VL

  SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQDSERPSGIP

  ERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID

  NO: 1934)

  >63A10.3 N20R C42S VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1935)

  >64B10.1 VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1936)

  >64B10.1 VH

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 1937)

  >66G2 VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ

  ID NO: 1938)

  >66G2 VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 1939)

  >67F5 VK

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 1940)

  >67F5 VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67C10 VK

  DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLS

  YRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR

  (SEQ ID NO: 1942)

  >67C10 VH

  EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW

  GQGTMVTVSS (SEQ ID NO: 1943)

  >68C8 VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8 VH

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1945)

  >49C8.1 VK.02

  DIQMTQSPSSLSASVGDRVTITCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETGV

  PSRFSGSGSGTDFTLTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ ID

  NO: 1946)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK.03

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTLTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1947)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK.04

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDFATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1948)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK.05

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDVATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1949)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK.06

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGQGTKVDLKR (SEQ

  ID NO: 1950)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK.07

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGGGTKVDLKR (SEQ

  ID NO: 1951)

  >49C8.1 VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1913)

  >49C8.1 VK

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1912)

  >49C8.1 VH.08

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQAPGQGLEWMGWMNPN

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1952)

  >49C8.1 VK

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1912)

  >49C8.1 VH.09

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIDWVRQATGQGLEWMGWMNPQ

  GGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1953)

  >49C8.1 VK

  DIQMTQSPSSLSASVGDRVTFTCQASQDINIYLNWYQQKPGKAPKLLIYDVSNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYFCQQYDNLPFTFGPGTKVDLKR (SEQ

  ID NO: 1912)

  >49C8.1 VH.10

  TGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAIYYCARGKEFSRAEFDYW

  GQGTLVTVSS (SEQ ID NO: 1954)

  >49H12 N83D VK.01

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTLTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ

  ID NO: 1955)

  >49H12 N83D VH

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1915)

  >49H12 N83D VK.02

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDFATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1956)

  >49H12 N83D VH

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1915)

  >49H12 N83D VK.03

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDVATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1957)

  >49H12 N83D VH

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1915)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH.04

  QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYDINWVRQATGQGPEWMGWMNPYS

  GSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFWG

  QGTMVTVSS (SEQ ID NO: 1958)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH.05

  QVQLVQSGAEVKKPGASVKVSCMASGYTFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1959)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH.06

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQAPGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1960)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH.07

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGYMNPYS

  GSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFWG

  QGTMVTVSS (SEQ ID NO: 1961)

  >49H12 N83D VK

  DIQMTQSPSSLSASVGDRVTITCQASQDITKYLNWYQQKPGKAPKLLIYDTFILETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLEIKR (SEQ ID

  NO: 1914)

  >49H12 N83D VH.08

  QVQLVQSGAEVKKPGASVKVSCMASGYIFTSYDINWVRQATGQGPEWMGWMNPY

  SGSTGYAQNFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNYNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1962)

  >49G3.3 VK.01

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTLTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1963)

  >49G3.3 VH

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1917)

  >49G3.3 VK.02

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDFATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1964)

  >49G3.3 VH

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1917)

  >49G3.3 VK.03

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDVATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1965)

  >49G3.3 VH

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1917)

  >49G3.3 VK.04

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGQGTKVEIRR (SEQ ID

  NO: 1966)

  >49G3.3 VH

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1917)

  >49G3.3 VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3 VH.05

  QVTLKESGPVLVKPTQTLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1967)

  >49G3.3 VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3 VH.06

  QVTLKESGPVLVKPTETLTLTCTFSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1968)

  >49G3.3 VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3 VH.07

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLAHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1969)

  >49G3.3_VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3_VH.08

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLGHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1970)

  >49G3.3_VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3_VH.09

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTLVTVSS (SEQ ID NO: 1971)

  >49G3.3_VK

  DIQMTQSPSSLSASIGDRVTITCQASQGISNYLNWYQQKPGKAPKLLIYDASNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCHQYDDLPLTFGGGTKVEIRR (SEQ ID

  NO: 1916)

  >49G3.3_VH.10

  QVTLKESGPVLVKPTETLTLTCTVSGFSLSNPRMGVSWIRQPPGKALEWLTHIFSNDE

  KSYSTSLKSRLTISKDTSKSQVVLSMTNMDPVDTATYYCVRVDTLNYHYYGMDVW

  GQGTMVTVSS (SEQ ID NO: 1972)

  >51A8.1_VL.01

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1973)

  >51A8.1_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1919)

  >51A8.1_VL.02

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKAEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1974)

  >51A8.1_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1919)

  >51A8.1_VL

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1918)

  >51A8.1_VH.03

  QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1975)

  >51A8.1_VL

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1918)

  >51A8.1_VH.04

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYEGS

  NKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYYG

  MDVWGQGTTVTVSS (SEQ ID NO: 1976)

  >51A8.1_VL

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1918)

  >51A8.1_VH.05

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARADGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1977)

  >51A8.1_VL

  NFILTQPHSVSESPGKTVTISCTRSSGSIASDYVQWYQQRPGSSPTTVIYEDKERSSGV

  PDRFSGSIDSSSNSASLTISGLKIEDEADYYCQSYDRNNHVVFGGGTKLTVLG (SEQ ID

  NO: 1918)

  >51A8.1_VH.06

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAEGDYPYYYYYY

  GMDVWGQGTTVTVSS (SEQ ID NO: 1978)

  >51E5.1_VK.01

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKRLIYAASSLQFG

  VPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1979)

  >51E5.1_VH

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1921)

  >51E5.1_VK.02

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNLLIYAASSLQFGV

  PSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1980)

  >51E5.1_VH

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1921)

  >51E5.1_VK.03

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNSLIYAASSLQFGV

  PSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1981)

  >51E5.1_VH

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1921)

  >51E5.1_VK.04

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFG

  VPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGQGTRVEIKR (SEQ ID

  NO: 1982)

  >51E5.1_VH

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1921)

  >51E5.1_VK

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFG

  VPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1920)

  >51E5.1_VH.05

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELEHSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1983)

  >51E5.1_VK

  DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPNRLIYAASSLQFG

  VPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHSSYPLTFGGGTRVEIKR (SEQ ID

  NO: 1920)

  >51E5.1_VH.06

  QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGELDTSGSI

  NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARVLGSTLDYWGQGTLVT

  VSS (SEQ ID NO: 1984)

  >52A8.1_VK.01

  DIQMTQSPSSLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1985)

  >52A8.1_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1923)

  >52A8.1_VK.02

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWYQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1986)

  >52A8.1_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1923)

  >52A8.1_VK.03

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWFQQKPGKAPKLLIYAASSLQSGVP

  SRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1987)

  >52A8.1_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1923)

  >52A8.1_VK.04

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIKR (SEQ ID

  NO: 1988)

  >52A8.1_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1923)

  >52A8.1_VK

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1922)

  >52A8.1_VH.05

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGYINPNS

  AATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1989)

  >52A8.1_VK

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1922)

  >52A8.1_VH.06

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSSLRSDDTAVYYCAREGGTYNWFDPWG

  QGTLVTVSS (SEQ ID NO: 1990)

  >52A8.1_VK

  DIQMTQSPSFLSASVGDRVTITCRASQTISSYLNWHQQKPGKAPKLLIYAASSLQSGV

  PSRFSGSGSGTDFSLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKR (SEQ ID

  NO: 1922)

  >52A8.1_VH.07

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGWINPN

  SAATNYAPKFQGRVTVTRDTSISTAYMELSRLRSDDTAVYYCAREGGTYNYFDPWG

  QGTLVTVSS (SEQ ID NO: 1991)

  >54A1.1_N83D_VK.01

  DIQMTQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1992)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.02

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQQKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1993)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.03

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1994)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.04

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTLTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1995)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.05

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDFATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1996)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.06

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDVATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1997)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.07

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGGGTKVDIKR (SEQ ID

  NO: 1998)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK.08

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGQGTKVDIKR (SEQ ID

  NO: 1999)

  >54A1.1_N83D_VH

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 1925)

  >54A1.1_N83D_VK

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1924)

  >54A1.1_N83D_VH.09

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 2000)

  >54A1.1_N83D_VK

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1924)

  >54A1.1_N83D_VH.10

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGYMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNWNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 2001)

  >54A1.1_N83D_VK

  DIQMAQSPSSLSASVGDRVTITCQASQDISIYLNWYQLKPGKAPKLLIYDVSNLETGV

  PSRFSGGGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGPGTKVDIKR (SEQ ID

  NO: 1924)

  >54A1.1_N83D_VH.11

  QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPH

  SGNTGYAQKFQGRVTMTRDTSINTAYMELSSLRSEDTAVYYCAKYNYNYGAFDFW

  GQGTMVTVSS (SEQ ID NO: 2002)

  >58C2.1_VK.01

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDEGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 2003)

  >58C2.1_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWND

  GNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYP

  YYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 1929)

  >58C2.1_VK

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 1928)

  >58C2.1_VH.02

  QVQLVESGGGVVQPGGSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWND

  GNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYP

  YYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2004)

  >58C2.1_VK

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 1928)

  >58C2.1_VH.03

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWNEG

  NNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYPY

  YFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2005)

  >58C2.1_VK

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 1928)

  >58C2.1_VH.04

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWND

  GNNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWNGYP

  YYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2006)

  >58C2.1_VK

  ENMTQTPLSLPVTPGEPASISCRSSQSLFDNDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRLEFPITFGQGTRLEIKR (SEQ

  ID NO: 1928)

  >58C2.1_VH.05

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVAVIWND

  GNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDQNYDFWQGYP

  YYFYYGMDVWGQGTTVTVSS (SEQ ID NO: 2007)

  >56E7.3_VK.01

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPKLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 2008)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.02

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 2009)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.03

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDFATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 2010)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.04

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGGGTTVDIKR (SEQ ID

  NO: 2011)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.05

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGQGTTVDIKR (SEQ ID

  NO: 2012)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.06

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTKVDIKR (SEQ ID

  NO: 2013)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK.07

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTRVDIKR (SEQ ID

  NO: 2014)

  >56E7.3_VH

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 1927)

  >56E7.3_VK

  378DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLE

  TGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ

  ID NO: 1926)

  >56E7.3_VH.08

  EVQLVQSGPEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSD

  TRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVT

  VSS (SEQ ID NO: 2015)

  >56E7.3_VK

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLET

  GVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ

  ID NO: 1926)

  >56E7.3_VH.09

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGESD

  TRYSPSFQGQVTISADTSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLVT

  VSS (SEQ ID NO: 2016)

  >56E7.3_VK

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 1926)

  >56E7.3_VH.10

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADKSISTAYLQWSRLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 2017)

  >56E7.3_VK

  DLQMTQSPSSLSASVGDRVTITCQASQDIKKFLNWYQQKPGKAPNLLIYDASNLETG

  VPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYAILPFTFGPGTTVDIKR (SEQ ID

  NO: 1926)

  >56E7.3_VH.11

  EVQLVQSGPEVKKPGESLKISCKGSGYSLTSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADTSISTAYLQWSSLKASDTAVYYCARAQLGIFDYWGQGTLV

  TVSS (SEQ ID NO: 2018)

  >60D7.1_N30T_VK.01

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLESDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2019)

  >60D7.1_N30T_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931)

  >60D7.1_N30T_VK.02

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDEGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2020)

  >60D7.1_N30T_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 1931)

  >60D7.1_N30T_VK

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2021)

  >60D7.1_N30T_VH.03

  QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 2022)

  >60D7.1_N30T_VK

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2021)

  >60D7.1_N30T_VH.04

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYEG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 2023)

  >60D7.1_N30T_VK

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2021)

  >60D7.1_N30T_VH.05

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFWSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 2024)

  >60D7.1_N30T_VK

  DIVLTQTPLSLPVTPGEPASISCRSSQSLLDSDDGDTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPLTFGGGTKVEIKR (SEQ

  ID NO: 2021)

  >60D7.1_N30T_VH.06

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDG

  SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVFYCARDQYFDFYSGYPFF

  YYYGMDVWGQGTTVTVSS (SEQ ID NO: 2025)

  >63A10.1_C58S_VL.01

  SYELTQPLSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2026)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.02

  SYELTQPPSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2027)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.03

  SYELTQPHSVSVALAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2028)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.04

  SYELTQPHSVSVAPAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2029)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.05

  SYELTQPHSVSVATGQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2030)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.06

  SYELTQPHSVSVATAQTARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGIP

  ERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2031)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.07

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQAPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2032)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.08

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQSPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2033)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.09

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQFPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2034)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.10

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSESNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2035)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.11

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNSGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2036)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.12

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIQAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2037)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.13

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWESSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2038)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL.14

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSEGVFGGGTKLTVLG (SEQ ID

  NO: 2039)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.15

  EVQLVESGGGLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2040)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.16

  EVQLVESGGDLVQPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2041)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.17

  EVQLVESGGDLVKPGGSLRLSCAVSGFTFSNAWMSWVRQAPGKGLEWVGRIKSKT

  DGGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVED

  YFDYWGQGTLVTVSS (SEQ ID NO: 2042)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.18

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVSRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2043)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.19

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTE

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2044)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.20

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDDSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2045)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.21

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDNSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2046)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.22

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKAEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2047)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.23

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCATDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2048)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.24

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTRDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2049)

  >63A10.1_C58S_VL

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVWDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 1932)

  >63A10.1_C58S_VH.25

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTESSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 2050)

  >63A10.1_C58S_VL.26

  SYELTQPHSVSVATAQMARITCGGNNIGSKAVHWYQQKPGQDPVLVIYSDSNRPSGI

  PERFSGSNPGNTATLTISRIEAGDEADYYCQVYDSSSDGVFGGGTKLTVLG (SEQ ID

  NO: 2051)

  >63A10.1_C58S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1933)

  >63A10.3_N20R_C42S_VL.01

  SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKPGQSPVLVIYQDSERPSGIP

  ERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID

  NO: 2052)

  >63A10.3_N20R_C42S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1935)

  >63A10.3_N20R_C42S_VL.02

  SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQESERPSGIPE

  RFSGSNSGNTATLTISGTQAMDEADYYCQAWDSTTVVFGGGTKLTVLG (SEQ ID

  NO: 2053)

  >63A10.3_N20R_C42S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1935)

  >63A10.3_N20R_C42S_VL.03

  SYELTQPPSVSVSPGQTARITCSGDKLGNRYTSWYQQKSGQSPVLVIYQDSERPSGIP

  ERFSGSNSGNTATLTISGTQAMDEADYYCQAWESTTVVFGGGTKLTVLG (SEQ ID

  NO: 2054)

  >63A10.3_N20R_C42S_VH

  EVQLVESGGDLVKPGGSLRLSCAVSGITFSNAWMSWVRQAPGKGLEWVGRIKSKTD

  GGTTDYAAPVKGRFTVSRDGSKNTLYLQMNSLKTEDTAVYYCTTDSSGSYYVEDYF

  DYWGQGTLVTVSS (SEQ ID NO: 1935)

  >64B10.1_VL.01

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLAITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2055)

  >64B10.1_VH

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 1937)

  >64B10.1_VL.02

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  20

  IPDRFSGSKSGTSATLGITGLQTEDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2056)

  >64B10.1_VH

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 1937)

  >64B10.1_VL.03

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWESSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2057)

  >64B10.1_VH

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 1937)

  >64B10.1_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1936)

  >64B10.1_VH.04

  QIQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 2058)

  >64B10.1_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1935)

  >64B10.1_VH.05

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTLVTVSS (SEQ ID NO: 2059)

  >64B10.1_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1935)

  >64B10.1_VH.06

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTMVTVSS (SEQ ID NO: 2060)

  >64B10.1_VL.07

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTYDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2061)

  >64B10.1_VH

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTWDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 1937)

  >64B10.1_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVAWYQQLPGTAPKLLIYDNDKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1935)

  >64B10.1_VH.08

  QIQLLESGPGLVKPSETLSLTCTVSGGSVSSGDYYWSWIRQPPGKGLEWIGFIYYSGG

  TNYNPSLKSRVTISIDTSKNQFSLKLNSVTAADTAVYYCARYSSTYDYYYGVDVWG

  QGTTVTVSS (SEQ ID NO: 2062)

  >66G2_VK.01

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 2063)

  >66G2_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 1939)

  >66G2_VK.02

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTEFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 2064)

  >66G2_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 1939)

  >66G2_VK.03

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTDFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 2065)

  >66G2_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 1939)

  >66G2_VK.04

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLQGYPLTFGGGTKVEIKR (SEQ ID

  NO: 2066)

  >66G2_VH

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 1939)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.05

  QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 2067)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.06

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYEGS

  NKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGMD

  VWGQGTTVTVSS (SEQ ID NO: 2068)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.07

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYAESVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGMD

  VWGQGTTVTVSS (SEQ ID NO: 2068)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.08

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYCATTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 2070)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.09

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCAKTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 2071)

  >66G2_VK

  DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASNLQSG

  VPSRFSGSGSGTKFTLTINSLQPEDFATYYCLQLNGYPLTFGGGTKVEIKR (SEQ ID

  NO: 1938)

  >66G2_VH.10

  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAGISYDG

  SNKNYADSVKGRITISRDNPKNTLYLQMNSLRAEDTAVYYCARTVTKEDYYYYGM

  DVWGQGTTVTVSS (SEQ ID NO: 2072)

  >67F5_VK.01

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIYGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 2073)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK.02

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLESADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 2074)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK.03

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQPADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 2075)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK.04

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSEDFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 2076)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK.05

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYYCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 2077)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPWTFGQGTKVEIKR (SEQ ID

  NO: 1940)

  >67F5_VH.06

  QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 2078)

  >67F5_VK.07

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIYPWTFGQGTKVEIKR (SEQ ID

  NO: 2079)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67F5_VK.08

  ENMTQSPATLSVSPGERVTLSCRASQSVSSNLAWYQQKPGQAPRLLIHGSSNRAIGIP

  ARFSGSGSGTEFTLTISSLQSADFAVYNCQQYEIWPYTFGQGTKVEIKR (SEQ ID

  NO: 2080)

  >67F5_VH

  QVQLKESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYSGNTN

  YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREYYYGSGSYYPWGQGTL

  VTVSS (SEQ ID NO: 1941)

  >67C10_VK.01

  DIVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLSY

  RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ

  ID NO: 2081)

  >67C10_VH

  EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW

  GQGTMVTVSS (SEQ ID NO: 1943)

  >67C10_VK.02

  DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDEGNTYLDWYLQKPGQSPQLLIYTLS

  YRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ

  ID NO: 2082)

  >67C10_VH

  EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW

  GQGTMVTVSS (SEQ ID NO: 1943)

  >67C10_VK

  DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLS

  YRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ

  ID NO: 1942)

  >67C10_VH.03

  EVQLVQSGAEVKKPGESLKISCKGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGDS

  DTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIW

  GQGTMVTVSS (SEQ ID NO: 2083)

  >67C10_VK

  DFVMTQTPLSLPVTPGEPASISCRSSQSLLNSDDGNTYLDWYLQKPGQSPQLLIYTLS

  YRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQRIEFPITFGQGTRLEIKR (SEQ

  ID NO: 1942)

  >67C10_VH.04

  EVQLVQSGAEVKKPGESLKISCQGSGYSFSSYWIGWVRQMPGKGLEWMGIIYPGESD

  TRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCARRASRGYRYGLAFAIWG

  QGTMVTVSS (SEQ ID NO: 2084)

  >68C8_VL.01

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLAITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2085)

  >68C8_VH

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1945)

  >68C8_VL.02

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTEDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2086)

  >68C8_VH

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1945)

  >68C8_VL.03

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWESSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2087)

  >68C8_VH

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1945)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.04

  QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 2088)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.05

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLDTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 2089)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.06

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCARYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 2090)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.07

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTLVTVSS (SEQ ID NO: 2091)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.08

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTMVTVSS (SEQ ID NO: 2092)

  >68C8_VL.09

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTYDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 2093)

  >68C8_VH

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDWDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 1945)

  >68C8_VL

  QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSG

  IPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLG (SEQ

  ID NO: 1944)

  >68C8_VH.10

  QVQLQESGPGLVKPSETLSLTCTVSGDSVSSGDNYWSWIRQPPGKGLEWIGFMFYSG

  STNYNPSLKSRVTISLHTSKNQFSLRLSSVTAADTAVYYCGRYRSDYDYYYGMDVW

  GQGTTVTVSS (SEQ ID NO: 2094)

Example 14 Immunogenicity Prediction
• Immune responses against proteins are enhanced by antigen processing and presentation in the major histocompatability complex (MHC) class II binding site. This interaction is required for T cell help in maturation of antibodies that recognize the protein. Since the binding sites of MHC class II molecules have been characterized, it is possible to predict whether proteins have specific sequences that can bind to a series of common human alleles. Computer algorithms have been created based on literature references and MHC class II crystal structures to determine whether linear 9 amino acid peptide sequences have the potential to break immune tolerance. We used the TEPITOPE™ program called to determine if point mutations of FGF21 are predicted to increase antigen specific T-cells in a majority of humans. Based on the linear protein sequence, none of the mutations examined are expected enhance immunogenicity. Results are shown in Table 17A and Table 17B below.

• TABLE 17A
  Protein	Predicted Immunogenicity
  Met-FGF21	Low
  Met-hFGF21(N106D)	Low
  Met-FGF21 (N122D)	Low
  hFc(R4).L15.hFGF21(G170E)	Low
  hFc(R4).L15.hFGF21(P171A)	Low
  hFc(R4).L15.hFGF21(S172L)	Low
  p30.hFc.L15.hFGF21(A45K, G170E)	Low
  p30.hFc.L15.hFGF21 (L98R, P171G)	Low

• TABLE 17B
  					LC				HC
  					Non-				Non-
  			LC	LC Non-	Tolerant		HC	HC Non-	tolerant
  	Predicted	LC Total	Tolerant	Tolerant	HLA	HC Total	Tolerant	tolerant	HLA
  Clone	immunogenicity	Agretopes	Agretopes	Agretopes	DRB1	Agretopes	Agretopes	Agretopes	DRB1
  68C8	Tier
  1	3	3	0	NA	12	12	0	NA
  63A10	Tier
  1	1	1	0	NA	12	12	0	NA
  51A8	Tier
  2	3	2	1	0101	16	16	0	NA
  					0701
  51E5	Tier	2	6	6	0	NA	11	10	1	0401
  									0701
  64B10	Tier	2	2	2	0	NA	12	11	1	0801
  49H12	Tier	3	7	5	2	0101	13	13	0	NA
  					0701
  					0801
  					1301
  					1501
  54A1	Tier	3	6	4	2	0301	14	14	0	NA
  					0801
  					1501
  52A8	Tier	3	6	5	1	0701	13	12	1	1301
  60D7	Tier	4	8	7	1	0301	16	14	2	0401
  					0401				1501
  					1101
  49C8	Tier	4	7	5	2	0801	14	13	1	0401
  					1501
  67C10	Tier	4	8	7	1	0301	14	12	2	0101
  					0401				701
  					1101

• Each reference cited herein is incorporated by reference in its entirety for all that it teaches and for all purposes.
• The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended as illustrations of individual aspects of the disclosure, and functionally equivalent methods and components form aspects of the disclosure. Indeed, various modifications of the disclosure, in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims.

Claims (8)

1-23. (canceled)

24. A method of preventing or treating a condition in a subject in need of such treatment comprising administering a therapeutically effective amount of isolated antigen binding protein that induces FGF21-mediated signaling, wherein the antigen binding protein comprises a light chain CDR1 comprising a sequence of SEQ ID NO: 821, a light chain CDR2 comprising a sequence of SEQ ID NO: 900, a light chain CDR3 comprising a sequence of SEQ ID NO: 954, a heavy chain CDR1 comprising a sequence of SEQ ID NO: 611, a heavy chain CDR2 comprising a sequence of SEQ ID NO: 664, and a heavy chain CDR3 comprising a sequence of SEQ ID NO: 741 to the subject, wherein the condition is treatable by lowering one or more of blood glucose, insulin or serum lipid levels.

25. The method of claim 24, wherein the antigen binding protein comprises one or more of:

(a) a light chain variable domain sequence comprising V_L47 of Table 2A (SEQ ID NO. 263);

(b) a heavy chain variable domain sequence comprising V_H46 of Table 2B (SEQ ID NO: 361); or

(c) a combination comprising a light chain variable domain of (a) and a heavy chain variable domain of (b).

26. The method of claim 25, wherein the light chain variable domain and the heavy chain variable domain comprise V_L47 and V_H46.

27. The method of claim 26, wherein the antigen binding protein comprises:

(a) a kappa light chain constant sequence of SEQ ID NO: 12

(b) a lambda light chain constant sequence of SEQ ID NO: 13

(c) a heavy chain constant sequence of SEQ ID NO: 11; or

(d) (i) the kappa light chain constant sequence of SEQ ID NO: 12 or the lambda light chain constant sequence of SEQ ID NO: 13, and

(ii) the heavy chain constant sequence of SEQ ID NO: 11.

28. The method of claim 24, wherein the antigen binding protein is a human antibody, a humanized antibody, chimeric antibody, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, an antigen-binding antibody fragment, a single chain antibody, a diabody, a triabody, a tetrabody, a Fab fragment, an F(fab′)₂ fragment, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4 antibody, or an IgG4 antibody having at least one mutation in the hinge region.

29. The method of claim 24, wherein the condition is diabetes, obesity, dyslipidemia, NASH, cardiovascular disease or metabolic syndrome.

30. The method of claim 29, wherein the condition is type 2 diabetes.

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